Amphotericin B

Pronunciation

Class: Polyenes
VA Class: AM700
CAS Number: 1397-89-3
Brands: Amphotec, Abelcet, AmBisome

Introduction

Antifungal; macrocyclic polyene.135 201 202 203 417

Uses for Amphotericin B

Aspergillosis

Treatment of invasive aspergillosis.146 201 203 204 207 211 219 230 231 232 235 236 237 238 239 240 241 242 243 244 248 268 269 288 396 379 420 423 436

IDSA considers voriconazole the drug of choice for primary treatment of invasive aspergillosis in most patients and IV amphotericin B liposomal the preferred alternative.423 Although conventional IV amphotericin B has historically been used for treatment of invasive aspergillosis, IDSA states that data to date indicate the lipid formulations of amphotericin B are as effective and less nephrotoxic and generally are preferred, if available.423 For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B (a lipid formulation), caspofungin, micafungin, posaconazole, or itraconazole.423 For empiric or preemptive therapy of presumed aspergillosis, IDSA recommends IV amphotericin B liposomal, caspofungin, itraconazole, or voriconazole.423

For HIV-infected adults and adolescents with invasive aspergillosis, CDC, NIH, and IDSA recommend voriconazole as drug of choice;440 IV amphotericin B (conventional or lipid formulation), IV echinocandins (caspofungin, micafungin, anidulafungin), and oral posaconazole are alternatives.440 Voriconazole also considered drug of choice for treatment of invasive aspergillosis in HIV-infected children;441 IV amphotericin B (conventional or lipid formulation) and IV caspofungin are alternatives.441

Blastomycosis

Treatment of pulmonary and extrapulmonary blastomycosis caused by Blastomyces dermatitidis.146 211 267 269 288 319 320 321 322 424 436 448 A drug of choice.146 227 267 283 319 320 424 436 448

IV amphotericin B is preferred for initial treatment of severe blastomycosis, especially infections involving the CNS,146 269 288 319 320 321 322 424 436 448 and for initial treatment of presumptive blastomycosis in immunocompromised patients, including HIV-infected individuals.267 424 Oral itraconazole is the drug of choice for treatment of mild to moderate pulmonary blastomycosis or mild to moderate disseminated blastomycosis (without CNS involvement) and also recommend for follow-up therapy in patients with more severe infections after an initial response has been obtained with IV amphotericin B.291 424 436

Conventional IV amphotericin B or a lipid formulation of IV amphotericin B can be used for initial treatment of blastomycosis.424 However, IDSA and others state that a lipid formulation (e.g., amphotericin B liposomal) is preferred for treatment of CNS blastomycosis since higher CSF concentrations may be obtained.424 448

IDSA states that long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole may be required to prevent relapse or recurrence of blastomycosis in immunocompromised patients and in other patients who experience relapse despite appropriate therapy.424 Such prophylaxis is not addressed in current CDC, NIH, and IDSA guidelines for prevention of opportunistic infections in individuals infected with HIV.440 441

Candida Infections

Treatment of disseminated or invasive infections caused by Candida, including candidemia, cardiovascular infections (endocarditis, pericarditis, myocarditis), or meningitis, and other serious Candida infections, including osteoarticular infections (osteomyelitis, septic arthritis), peritonitis, intra-abdominal abscesses, urinary tract infections (symptomatic cystitis, pyelonephritis, urinary fungus balls), and endophthalmitis.126 211 146 222 223 224 225 248 254 283 436 Also used for treatment of certain severe or refractory mucocutaneous Candida infections.425 436 440

Generally effective against infections caused by C. albicans, C. glabrata, C. krusei, C. parapsilosis, or C. tropicalis.223 254 425 A drug of choice for many infections caused by fluconazole-resistant Candida.425

Choice of an antifungal for treatment of candidemia or invasive Candida infections should take into consideration any history of recent exposure to azole antifungals or intolerance to antifungals, local and/or institutional epidemiologic data regarding prevalence of the various Candida strains and their patterns of resistance, severity of illness, relevant comorbidities, presence and duration of neutropenia or immunosuppression, and evidence of involvement of the CNS, cardiac valves, and/or visceral organs.425 Amphotericin B generally is preferred for severe Candida infections caused by strains that may be fluconazole-resistant (e.g., C. glabrata, C. krusei) and for treatment of Candida infections in patients who have recently received fluconazole or are immunocompromised (e.g., those with HIV infection).227 288 346 347 425 436

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;425 amphotericin B (conventional or lipid formulation) is an alternative when these drugs have been ineffective or cannot be used because of intolerance or resistance.425 Initial therapy with an echinocandin is preferred in patients with moderately severe to severe infections and for those who recently received an azole antifungal or are likely to be infected with C. glabrata or C. krusei;425 consider transition from the echinocandin to fluconazole in clinically stable patients if strains susceptible to fluconazole (e.g., C. albicans) are likely.425 Fluconazole is the drug of choice for treatment of infections caused by C. parapsilosis in these patients.425

For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B (a lipid formulation) for initial therapy;425 fluconazole is a reasonable alternative in those who are less critically ill or have not recently received an azole;425 voriconazole can be used as an alternative when broader antifungal coverage is required.425 An echinocandin, amphotericin B (a lipid formulation), or voriconazole recommended for C. krusei infections.425 An echinocandin is preferred for C. glabrata infections;425 fluconazole or amphotericin B (a lipid formulation) is preferred for C. parapsilosis infections.425 For infections known to be caused by C. krusei, an echinocandin, amphotericin B (a lipid formulation), or voriconazole recommended.425 For initial empiric treatment of suspected invasive candidiasis in neutropenic patients, amphotericin B (a lipid formulation), caspofungin, or IV voriconazole recommended;425 alternatives are fluconazole or itraconazole.425

Conventional IV amphotericin B usually is the drug of choice for treatment of disseminated candidiasis in neonates (neonatal candidiasis).146 425 IDSA states that fluconazole is a reasonable alternative if amphotericin B cannot be used.425

For treatment of CNS candidiasis, IDSA recommends initial treatment with IV amphotericin B (with or without oral flucytosine) and follow-up treatment with fluconazole.425 A lipid formulation of IV amphotericin B may be preferred, but conventional IV amphotericin B can be used.425 Conventional amphotericin B has been given intrathecally as an adjunct to systemic antifungal for treatment of Candida meningitis.126 211 455

Mucocutaneous or noninvasive Candida infections (e.g., oropharyngeal, esophageal, or vaginal candidiasis) usually can be adequately treated with an appropriate oral or topical antifungal.147 269 283 425 436 Severe mucocutaneous infections (e.g., oropharyngeal candidiasis, esophageal candidiasis) caused by azole-resistant Candida or infections that fail to respond to such therapy may require IV amphotericin B.146 425 436 Also has been recommended as an alternative for treatment of oropharyngeal candidiasis or esophageal candidiasis in patients who cannot tolerate oral therapy.425 440

Treatment of urinary tract infections caused by Candida.126 146 211 232 251 260 262 292 425 436 433 434 435 466 467 468 469 470 471 472 473 474 IDSA states that antifungal treatment not usually indicated for asymptomatic cystitis, unless there is high risk of disseminated candidiasis (e.g., neutropenic patients, low birthweight infants, patients undergoing renal transplantation or urologic manipulations).425 If treatment is indicated, fluconazole usually is the drug of choice for symptomatic cystitis, pyelonephritis, or fungus balls likely to be caused by fluconazole-susceptible Candida.425 When fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) are likely, IV amphotericin B or oral flucytosine recommended for symptomatic cystitis, IV amphotericin B (with or without flucytosine) or oral flucytosine alone recommended for pyelonephritis, and IV amphotericin B (with or without flucytosine) recommended for fungus balls.425

Has been administered by bladder irrigation for treatment of candiduria (funguria),126 146 211 232 251 260 262 292 425 433 434 435 466 467 468 469 470 471 472 473 474 but such therapy is controversial.292 434 467 468 469 471 472 473 474 IDSA states that bladder irrigation with amphotericin B is not generally recommended, but may be useful for patients with refractory symptomatic cystitis caused by fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) or as an adjunct to systemic antifungal therapy for the treatment of urinary fungus balls,425

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Treatment of endophthalmitis caused by Candida.425 IDSA states that IV amphotericin B (conventional formulation) used in conjunction with flucytosine is the regimen of choice in patients with advancing lesions or lesions threatening the macula;425 fluconazole is an acceptable alternative for less severe endophthalmitis.425 Ophthalmic consultation for consideration of partial vitrectomy and intravitreal administration of conventional amphotericin B recommended for patients with severe endophthalmitis and vitreitis.425

Coccidioidomycosis

Treatment of coccidioidomycosis caused by Coccidioides immitis or C. posadasii.126 135 146 248 269 285 288 385 394 396 426 436 440

Antifungal treatment may not be necessary for mild, uncomplicated coccidioidal pneumonia since such infections may resolve spontaneously;426 treatment recommended for patients with more severe or rapidly progressing infections, those with chronic pulmonary or disseminated infections, and immunocompromised or debilitated individuals (e.g., HIV-infected individuals, organ transplant recipients, those receiving immunosuppressive therapy, those with diabetes or cardiopulmonary disease).426 440 441

For initial treatment of symptomatic pulmonary coccidioidomycosis and chronic fibrocavitary or disseminated (extrapulmonary) coccidioidomycosis, IDSA states that an oral azole (fluconazole or itraconazole) usually recommended.426 IV amphotericin B recommended as an alternative and is preferred for initial treatment of severely ill patients who have hypoxia or rapidly progressing disease, for immunocompromised individuals, or when azole antifungals cannot be used (e.g., pregnant women).146 426

For HIV-infected adults and adolescents with clinically mild coccidioidomycosis (e.g., focal pneumonia), CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole for initial treatment.440 For treatment of diffuse pulmonary infections or extrathoracic disseminated coccidioidomycosis (nonmeningeal) in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B followed by an oral azole.440 Alternatively, some experts recommend initial treatment with IV amphotericin B in conjunction with an oral azole (fluconazole or itraconazole) followed by the oral azole alone.440

For HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B followed by oral fluconazole or oral itraconazole.441 In those with severe disseminated disease, some experts recommend initial therapy with IV amphotericin B used in conjunction with an oral azole (e.g., fluconazole) followed by an oral azole alone.441 Use of fluconazole or itraconazole alone may be sufficient for treatment of coccidioidomycosis in those with only mild disease (e.g., focal pneumonia) and also can be considered an alternative for those with stable pulmonary or disseminated coccidioidomycosis (nonmeningeal).441

For treatment of coccidioidal meningitis in HIV-infected adults, adolescents, or children or for other individuals, fluconazole (with or without intrathecal amphotericin B) is the regimen of choice;146 426 440 441 itraconazole is an alternative in adults and adolescents.426 440 If patient does not respond to azole therapy alone, consider intrathecal amphotericin B (with or without continued azole therapy) or IV amphotericin B used in conjunction with intrathecal amphotericin B.146 426 440 441 Consultation with an expert recommended.146 440 441

Long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral itraconazole recommended to prevent relapse or recurrence of coccidioidomycosis in HIV-infected individuals who have been adequately treated for the disease.440 441 Secondary prophylaxis with oral fluconazole or oral itraconazole also necessary in any other individual treated for coccidioidal meningitis.146 426

Cryptococcosis

Treatment of infections caused by Cryptococcus neoformans.126 135 145 146 153 158 162 169 170 177 182 183 184 188 189 196 197 201 202 211 213 214 215 216 220 230 231 269 393 427 436 440 A drug of choice, especially for initial treatment of meningitis.126 135 145 146 153 158 162 169 170 177 182 183 184 196 197 211 213 214 269 393 427 436 440 Because of reported in vitro and in vivo synergism, usually used in conjunction with flucytosine for initial treatment,146 197 211 213 214 346 427 440 including in HIV-infected patients.145 146 169 172 182 183 185 192 427 440

For HIV-infected adults and adolescents with cryptococcal meningitis, CDC, NIH, and IDSA state that the preferred regimen is initial (induction) therapy with IV amphotericin B liposomal given in conjunction with oral flucytosine for at least 2 weeks and until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then follow-up (consolidation) therapy with oral fluconazole administered for at least 8 weeks, followed by long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole to complete at least 1 year of azole therapy.440

Preferred alternative for initial (induction) therapy for treatment of cryptococcal meningitis in HIV-infected adults and adolescents is IV amphotericin B lipid complex in conjunction with oral flucytosine;440 other alternatives are conventional IV amphotericin B in conjunction with oral flucytosine; IV amphotericin B liposomal or conventional IV amphotericin B in conjunction with oral or IV fluconazole; IV amphotericin B liposomal alone; oral or IV fluconazole in conjunction with oral flucytosine; or oral or IV fluconazole alone.440

Alternative regimens may be less effective and are recommended only in patients who cannot tolerate or have not responded to the preferred regimen.427 440 IDSA states that use of intrathecal or intraventricular conventional amphotericin B in the treatment of cryptococcal meningitis generally is discouraged and rarely necessary.427

For treatment of cryptococcal CNS infections in organ transplant recipients, IDSA recommends induction therapy with IV amphotericin B liposomal or amphotericin B lipid complex given in conjunction with oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole given for 8 weeks.427 Induction regimen should be continued for at least 4–6 weeks if flucytosine isn't included.427 Conventional amphotericin B not usually recommended for first-line treatment of cryptococcosis in transplant recipients because of the risk of nephrotoxicity.427

In adults and children who do not have HIV infection and are not transplant recipients, IDSA states that the preferred regimen for treatment of cryptococcal meningitis is induction therapy with conventional IV amphotericin B given in conjunction with oral flucytosine for at least 4 weeks (consider a 2-week induction period in those who are immunocompetent, are without uncontrolled underlying disease, and are at low risk for therapeutic failure), then consolidation therapy with oral fluconazole administered for an additional 8 weeks or longer.427

For treatment of mild to moderate pulmonary cryptococcosis (nonmeningeal) in immunocompetent or immunosuppressed adults or children, IDSA states that the regimen of choice is oral fluconazole given for 6–12 months.427 However, severe pulmonary cryptococcosis, cryptococcemia, and disseminated cryptococcal infections in immunocompetent or immunosuppressed adults, adolescents, or children should be treated using regimens recommended for cryptococcal meningitis.427 440 441

Alternative to oral fluconazole for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent relapse of cryptococcal meningitis in HIV-infected individuals.155 160 169 177 185 197 213 427 Oral fluconazole is drug of choice for secondary prophylaxis of cryptococcosis in HIV-infected adults, adolescents, and children or other individuals who have had documented, adequately treated cryptococcal meningitis;427 440 441 conventional IV amphotericin B may be less effective and should be used only if necessary in those who cannot receive azole antifungals.427

Although data are limited, IDSA states that recommendations for treatment of CNS, pulmonary, or disseminated infections caused by Cryptococcus gattii and recommendations for secondary prophylaxis of C. gattii infections are the same as recommendations for C. neoformans infections.427 IDSA states that single, small cryptococcoma may be treated with oral fluconazole; induction therapy with a regimen of conventional IV amphotericin B and flucytosine given for 4–6 weeks, followed by consolidation therapy with fluconazole given for 6–18 months, should be considered for very large or multiple cryptococcomas caused by C. gattii.427 Regimens that include amphotericin B (conventional or liposomal formulations), flucytosine, and fluconazole have been effective in a few patients with CNS infections known to be caused by C. gattii.450 451 454

Exserohilum Infections

Treatment of infections known or suspected to be caused by Exserohilum rostratum.476 477 484 485 487 489 490 491 492

Exserohilum, a common mold found in soil and on plants (especially grasses),477 478 481 482 is rarely involved in human infections.478 480 481 482 487 E. rostratum has caused cutaneous and subcutaneous infections or keratitis, typically from skin or eye trauma;478 480 481 482 487 also has rarely caused more invasive or life-threatening infections (e.g., sinuses, heart, lungs, bones), usually in immunocompromised individuals.478 480 481 482 487 Exserohilum infections cannot be transmitted person-to-person.478

Although data limited and clinical relevance of in vitro testing remains uncertain,477 480 Exserohilum is inhibited in vitro by some triazole antifungals (e.g., voriconazole, itraconazole, posaconazole) and amphotericin B;477 480 481 482 489 echinocandins (e.g., caspofungin, micafungin) have variable in vitro activity480 481 482 and fluconazole has poor in vitro activity against the fungus.481

E. rostratum was the predominant pathogen in the 2012–2013 US outbreak of fungal meningitis and other fungal infections in patients who received contaminated preservative-free methylprednisolone acetate injections prepared by a compounding pharmacy (New England Compounding Center [NECC]).477 478 488 490 491

As of September 6, 2013, total of 750 cases of fungal infections (including 64 deaths) reported in 20 states and linked to 3 lots of contaminated methylprednisolone acetate injections.477 Majority of initial cases involved fungal meningitis (some with stroke);477 483 486 488 490 491 492 subsequent reports involved localized spinal or paraspinal infections (e.g., epidural abscess).477 483 486 491 More than 6 months after the outbreak, CDC continued to receive reports of patients presenting with localized spinal and paraspinal infections (e.g., epidural abscess, phlegmon, discitis, vertebral osteomyelitis, arachnoiditis, or other complications at or near the injection site).477 483 486 Localized infections have occurred in patients with or without a diagnosis of fungal meningitis.477 483

Consultation with an infectious disease expert recommended to assist with diagnosis, management, and follow-up, which may be complex and prolonged.484 485 Clinical consultant network for clinicians can be reached by calling CDC at 800-232-4636.484 485

Because of evidence of latent disease, CDC cautions clinicians to maintain high index of suspicion and remain vigilant for fungal infections in patients who received the contaminated products (especially in those who have mild or baseline symptoms) and to consider MRI evaluation for localized infections if clinically warranted.483 486

Consult most recent CDC treatment guidance documents () for the most current recommendations for selection of antifungal agents and appropriate dosages and duration of treatment for CNS and parameningeal infections and osteoarticular infections associated with the contaminated methylprednisolone acetate products.477 The following information was current when the amphotericin B monograph was finalized for production.477

For treatment of CNS infections (including meningitis, stroke, and arachnoiditis) and/or parameningeal infections (epidural or paraspinal abscess, discitis or osteomyelitis, and sacroiliac infection) in adults who received contaminated methylprednisolone acetate injections, CDC recommends voriconazole.484 In most of these patients, use IV voriconazole initially; consider transitioning to oral voriconazole only after patient is clinically stable or improving and consider initial treatment with oral voriconazole only in those with mild disease who can be monitored closely.484 Strongly consider use of IV amphotericin B liposomal in addition to IV voriconazole in patients who present with severe disease and in those who do not improve or experience clinical deterioration or manifest new sites of disease activity while receiving voriconazole monotherapy.484 IV amphotericin B liposomal also is an alternative in patients unable to tolerate voriconazole.484 Although posaconazole or itraconazole has been used in some patients who could not tolerate voriconazole or amphotericin B, efficacy for treatment of these fungal infections not established; expert consultation advised when making decisions regarding alternative regimens.484

For treatment of osteoarticular infections (discitis, vertebral osteomyelitis, and epidural abscess or osteoarticular infections not involving the spine) in adults who received intra-articular injections of contaminated methylprednisolone acetate injections, CDC recommends voriconazole.485 Use IV voriconazole initially in those with more severe osteoarticular infections, clinical instability, discitis, vertebral osteomyelitis, or epidural abscess; consider transitioning to oral voriconazole only after patient is clinically stable or improving and consider initial treatment with oral voriconazole only in patients with mild osteoarticular infections not involving the spine who can be monitored closely.485 Consider use of a lipid formulation of IV amphotericin B in addition to IV voriconazole in patients with severe osteoarticular infection and/or clinical instability.485 A lipid formulation of IV amphotericin B, posaconazole, or itraconazole are alternatives in patients who cannot tolerate voriconazole; expert consultation advised when making decisions regarding alternative regimens.485

Adequate duration of antifungal treatment for these Exserohilum infections not known, but prolonged therapy (at least 3–6 months) required.484 485 (See Exserohilum Infections under Dosage and Administration.) Close follow-up monitoring after completion of treatment is essential in all patients to detect potential relapse.484 485

Consult CDC website at and FDA website at for most recent information.477 CDC website includes information regarding case definitions and diagnostic testing as well as management and treatment of these infections.477

Fusarium Infections

Treatment of serious fungal infections caused by Fusarium.57 436 A drug of choice.57 436

Select most appropriate antifungal based on in vitro susceptibility testing.57 Amphotericin B may be preferred for infections caused by F. solani or F. verticillioides;57 either voriconazole or amphotericin B recommended for other Fusarium infections.57

Histoplasmosis

Treatment of histoplasmosis caused by Histoplasma capsulatum.126 146 269 288 428 436

IV amphotericin B and oral itraconazole are the drugs of choice for treatment of histoplasmosis.146 227 248 269 283 318 436 IV amphotericin B is preferred for initial treatment of severe, life-threatening histoplasmosis, especially in immunocompromised patients (e.g., those with HIV infection).126 146 197 227 269 283 288 318 428 436 Oral itraconazole generally used for initial treatment of less severe disease (e.g., mild to moderate acute pulmonary histoplasmosis, chronic cavitary pulmonary histoplasmosis) and as follow-up therapy in severe infections after a response has been obtained with amphotericin B.227 283 288 318 428 436 440 441

For HIV-infected adults and adolescents with moderately severe to severe acute pulmonary histoplasmosis or progressive disseminated histoplasmosis, CDC, NIH, and IDSA recommend initial (induction) treatment with IV amphotericin B liposomal and follow-up treatment with oral itraconazole.440 Alternatively, if necessary because of cost or tolerability, other lipid formulations of amphotericin B can be used.440

For treatment of progressive disseminated histoplasmosis in children, IDSA states that conventional IV amphotericin B or an initial regimen of conventional IV amphotericin B and follow-up treatment with oral itraconazole can be used.428 IDSA states that conventional amphotericin B usually is well tolerated in children, but a lipid formulation may be substituted if necessary.428 For treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected infants and children, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B liposomal and follow-up treatment with oral itraconazole;441 conventional IV amphotericin B can be used as an alternative to the lipid formulation for initial treatment in these children.441 Although oral itraconazole may be used alone for treatment of mild to moderate disseminated histoplasmosis in children, including HIV-infected infants and children, it is not recommended for more severe infections.428 441

For treatment of meningitis caused by H. capsulatum in HIV-infected adults, adolescents, or children and in other individuals, CDC, NIH, and IDSA recommend initial (induction) treatment with IV amphotericin B liposomal and follow-up treatment with oral itraconazole.428 440 441 Amphotericin B liposomal generally preferred for treatment of CNS histoplasmosis428 440 441 because higher CSF concentrations may be obtained than with some other amphotericin B formulations.428 441

Long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole recommended to prevent relapse or recurrence of histoplasmosis in HIV-infected adults, adolescents, and children and other immunosuppressed individuals who have been adequately treated for histoplasmosis.428 440 441

Paracoccidioidomycosis

Treatment of paracoccidioidomycosis (South American blastomycosis) caused by Paracoccidioides brasiliensis.126 146 221 282 288 436

IV amphotericin B is drug of choice for initial treatment of severe paracoccidioidomycosis.126 146 221 282 436 Oral itraconazole is drug of choice for treatment of less severe or localized paracoccidioidomycosis and for follow-up therapy in more severe infections after initial treatment with IV amphotericin B.126 146

Penicilliosis

Treatment of penicilliosis caused by Penicillium marneffei.406 407 408 410 440

For treatment of severe or disseminated P. marneffei infections, an initial regimen of IV amphotericin B followed by oral itraconazole recommended.406 407 410 440 Oral itraconazole can be used alone for treatment of mild infections.440

For HIV-infected adults and adolescents with severe acute penicilliosis, CDC, NIH, and IDSA recommend treatment with IV amphotericin B liposomal initially followed by oral itraconazole.440 Voriconazole is an alternative, and may be used in those who do not respond to amphotericin B followed by itraconazole.440

Long-term suppressive or maintenance therapy (secondary prophylaxis) with itraconazole recommended to prevent relapse of penicilliosis in HIV-infected adults and adolescents who were treated for penicilliosis.407 408 440

Sporotrichosis

Treatment of disseminated, pulmonary, osteoarticular, and meningeal sporotrichosis caused by Sporothrix schenckii.126 146 211 269 288 289 291 417 429 436

IV amphotericin B is the drug of choice for initial treatment of severe, life-threatening sporotrichosis and sporotrichosis that is disseminated or has CNS involvement.126 288 289 291 429 436 Oral itraconazole is considered the drug of choice for treatment of cutaneous, lymphocutaneous, or mild pulmonary or osteoarticular sporotrichosis and for follow-up treatment of severe infections after a response has been obtained with IV amphotericin B.288 289 291 429 436

IDSA and others state that a lipid formulation of amphotericin B is preferred for treatment of sporotrichosis since the lipid formulations generally are associated with fewer adverse effects.429 436

Zygomycosis

Treatment of zygomycosis, including mucormycosis, caused by susceptible species of Absidia, Mucor, or Rhizopus and treatment of infections caused by susceptible species of Conidiobolus or Basidiobolus.126 231 232 384 126 135 269 324 366 367 396 465

Drug of choice for zygomycosis.269 324 However, severe cases of GI basidiobolomycosis caused by Basidiobolus ranarum may not respond to amphotericin B.413 414 415 416 GI basidiobolomycosis has been successfully treated with oral itraconazole after partial surgical resection of the GI tract.413 415 416

Empiric Therapy in Febrile Neutropenic Patients

Empiric therapy of presumed fungal infections in febrile, neutropenic patients who have not responded to empiric treatment with broad-spectrum antibacterial agents.126 195 202 248 252 273 277 290 344 372 373 374 376 422 452

Conventional IV amphotericin B historically has been the drug of choice for empiric antifungal treatment in patients who remain febrile and neutropenic despite 4–7 days of empiric treatment with an appropriate broad-spectrum antibacterial agent;422 lipid formulations of amphotericin B or other antifungals (e.g., caspofungin, voriconazole) also have been used.422

Consult published protocols on treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of initial empiric regimen, when to change initial regimen, possible subsequent regimens, and duration of therapy in these patients.422 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also advised.422

Prevention of Fungal Infections in Transplant Recipients, Cancer Patients, or Other Patients at High Risk

Prevention of fungal infections (e.g., aspergillosis, candidiasis) in neutropenic cancer patients or patients undergoing BMT or solid organ transplantation.126 211 249 274 277 286 287 358 371 372 375 422

For postoperative antifungal prophylaxis in recipients of solid organ transplants at high risk for invasive candidiasis (i.e., liver, pancreas, or small bowel transplant recipients), IDSA recommends fluconazole or IV amphotericin B liposomal.425 Risk of invasive candidiasis after other solid organ transplants (e.g., kidney, heart) appears to be too low to warrant routine antifungal prophylaxis.425

Conventional amphotericin B,211 243 261 276 286 287 460 463 amphotericin B lipid complex,423 460 461 and amphotericin B liposomal460 462 464 have been administered by nasal instillation or nebulization in an attempt to prevent aspergillosis in immunocompromised patients, including solid organ transplant recipients (e.g., lung transplant recipients) and neutropenic chemotherapy patients.

Leishmaniasis

Treatment of American cutaneous leishmaniasis caused by Leishmania braziliensis or L. mexicana and for mucocutaneous leishmaniasis caused by L. braziliensis.102 103 104 105 106 107 108 109 126 135 269 271 381 442 443 Drugs of choice for cutaneous or mucocutaneous leishmaniasis are sodium stibogluconate (not commercially available in the US, but may be available from CDC), meglumine antimonate (not commercially available in the US), and miltefosine (not commercially available in the US, but may be available from CDC);256 271 381 442 amphotericin B is an additional drug of choice for mucosal infections.271 381 442 443

Treatment of visceral leishmaniasis (kala-azar).108 115 116 117 126 135 187 202 247 253 256 382 383 404 442 443 444 Drugs of choice for initial treatment of visceral leishmaniasis caused by L. donovani (usually endemic in Asia and Africa), L. infantum (usually endemic in the Mediterranean basin), or L. chagasi (usually endemic in Latin America) are amphotericin B (lipid formulation), sodium stibogluconate (not commercially available in the US, but may be available from CDC), meglumine antimonate (not commercially available in the US), and miltefosine (not commercially available in the US, but may be available from CDC);108 117 246 256 259 271 384 442 443 444 amphotericin B (conventional formulation) is considered an alternative.126 256 257 271 442 443

For HIV-infected adults and adolescents with cutaneous, mucocutaneous, or diffuse cutaneous leishmaniasis, CDC, NIH, and IDSA recommend amphotericin B liposomal or sodium stibogluconate (not commercially available in the US, but may be available from CDC) as the drugs of choice for treatment.440 Potential treatment alternatives are miltefosine (not commercially available in the US, but may be available from CDC), topical paromomycin, intralesional pentavalent antimony, and local heat therapy; efficacy of these alternatives depends on the infecting species of Leishmania.440

For HIV-infected adults and adolescents with visceral leishmaniasis, CDC, NIH, and IDSA recommend amphotericin B liposomal as the drug of choice for treatment;440 treatment alternatives are amphotericin B lipid complex, conventional amphotericin B, sodium stibogluconate (not commercially available in the US, but may be available from CDC), miltefosine (not commercially available in the US, but may be available from CDC), and paromomycin.440

Long-term suppressive or maintenance therapy (secondary prophylaxis) to decrease the risk of relapse in HIV-infected individuals who have been treated for visceral leishmaniasis and have CD4+ T-cells <200/mm3.440 Although data are limited, these experts state that secondary prophylaxis also should be offered to HIV-infected individuals who have been adequately treated for cutaneous leishmaniasis but are immunocompromised and have had multiple relapses.440 If secondary prophylaxis against leishmaniasis is indicated, CDC, NIH, and IDSA recommend amphotericin B liposomal or amphotericin B lipid complex; sodium stibogluconate (not commercially available in the US, but may be available from CDC) is an alternative.440 Manufacturer of amphotericin B liposomal states that, while it may have a role for long-term suppressive therapy to prevent relapse of visceral leishmaniasis in HIV-infected individuals, efficacy and safety of repeated courses or maintenance therapy with the drug in immunocompromised individuals has not been evaluated to date.202

Individualize treatment of leishmaniasis (e.g., drug, dosage, duration of treatment) based on region where the disease was acquired, likely infecting species, and patient factors (e.g., immune status).442 Consultation with clinicians experienced in management of the disease recommended.442

Primary Amebic Meningoencephalitis

Treatment of primary amebic meningoencephalitis caused by Naegleria fowleri.119 126 146 442

These infections usually are rapidly fatal, but there have been a few reports of successful treatment with conventional amphotericin B used alone122 123 124 146 or in conjunction with other drugs (e.g., rifampin and chloramphenicol; rifampin and ketoconazole; miconazole [no longer commercially available], rifampin, and sulfadiazine).123 124 126 146 442 Concomitant IV and intrathecal conventional amphotericin B has been recommended.118 119 122 124 125

Amphotericin B Dosage and Administration

Administration

Administer conventional amphotericin B,135 417 amphotericin B cholesteryl sulfate complex,203 amphotericin B lipid complex,201 and amphotericin B liposomal by IV infusion. (See Acute Infusion Reactions under Cautions.)202

Conventional amphotericin B also has been given intra-articularly,456 intrapleurally,475 intrathecally,126 211 426 440 441 455 457 by nasal instillation or nebulization,211 243 261 276 286 287 460 463 and by bladder irrigation.126 146 211 232 251 260 262 292 425 432 433 434 435 466 467 468 469 470 471 472 473 474 Amphotericin B lipid complex423 460 461 and amphotericin B liposomal460 462 464 also have been administered by nasal inhalation or nebulization.

IV Administration of Conventional Amphotericin B

Reconstitution and Dilution

Conventional amphotericin B must be reconstituted and diluted prior to administration.135 417

Reconstitute 50-mg vial by adding 10 mL of sterile water for injection (without bacteriostatic agent) to provide a solution containing 5 mg/mL.135 417 Add sterile water diluent rapidly to the vial using a sterile syringe and 20-gauge needle; immediately shake vial until colloidal dispersion is clear.135 417 For IV infusion, the colloidal dispersion is further diluted (usually to a concentration of 0.1 mg/mL) with 500 mL of 5% dextrose injection (the dextrose injection must have a pH exceeding 4.2).135 417 Although pH of commercially available 5% dextrose injection usually is >4.2, pH of each container of 5% dextrose injection should be determined and, if pH is low, it may be adjusted with a sterile buffer solution in accordance with instructions provided by the manufacturers.135 417

Rate of Administration

Administer conventional amphotericin B by IV infusion slowly over a period of approximately 2–6 hours, depending on dose.135 345 360 417

IV infusions given over 1–2 hours may be tolerated in some patients,345 346 359 360 361 362 but manufacturers and many clinicians state that rapid IV infusion should be avoided since potentially serious adverse effects (e.g., hypotension, hypokalemia, arrhythmias, shock) may occur.135 264 359 360 362 417

An inline membrane filter may be used; to ensure passage of amphotericin B colloidal dispersion, the mean pore diameter of the filter should not be <1 mcm.135 417

IV Administration of Amphotericin B Cholesteryl Sulfate Complex (Amphotec)

Reconstitution and Dilution

Amphotericin B cholesteryl sulfate complex must be reconstituted and diluted prior to administration.203

Reconstitute 50 or 100 mg vial by adding 10 or 20 mL, respectively, of sterile water for injection to provide a colloidal dispersion containing 5 mg/mL.203 Add sterile water diluent rapidly to the vial using a sterile syringe and 20-gauge needle; shake vial gently by hand until all solids have dissolved.203 The reconstituted colloidal dispersion must be further diluted in 5% dextrose injection to provide a final concentration of approximately 0.6 mg/mL (range: 0.16–0.83 mg/mL).203

Do not reconstitute with solutions containing sodium chloride or dextrose.203 Reconstituted drug should not be admixed with other drugs or any solution containing sodium chloride or electrolytes.203

Should not be filtered prior to administration and should not be administered using an inline filter.203 Administer using a separate infusion line; if an existing IV line is used, it should be flushed with 5% dextrose injection before amphotericin B cholesteryl sulfate complex is infused.203

Rate of Administration

Administer amphotericin B cholesteryl sulfate complex by IV infusion at a rate of 1 mg/kg per hour.203

Each time a new course of amphotericin B cholesteryl sulfate complex is administered, it may be advisable to administer a small test dose immediately prior to the first dose (e.g., 10 mL of a solution containing 1.6–8.3 mg given over 15–30 minutes) and observe the patient over the next 30 minutes.203 If well tolerated, the infusion time may be shortened to a minimum of 2 hours; infusion time may need to be lengthened in patients who experience acute reactions or cannot tolerate the infusion volume.203

IV Administration of Amphotericin B Lipid Complex (Abelcet)

Dilution

Amphotericin B lipid complex suspension concentrate must be diluted prior to administration.201

Dilute in 5% dextrose injection to a concentration of 1 mg/mL according to the manufacturer's directions; a concentration of 2 mg/mL may be appropriate for pediatric patients and patients with cardiovascular disease.201

Solutions containing sodium chloride or bacteriostatic agents should not be used, and the drug should not be mixed with other drugs or with electrolytes.202

Prior to administration, the IV container of diluted drug should be shaken until the contents are thoroughly mixed; the infusion container should then be shaken every 2 hours if the infusion time is >2 hours.201

Administer using a separate infusion line; if an existing IV line is used, it should be flushed with 5% dextrose injection before amphotericin B lipid complex is infused.201 An inline membrane filter should not be used during administration of amphotericin B lipid complex.201

Rate of Administration

Administer amphotericin B lipid complex by IV infusion at a rate of 2.5 mg/kg per hour.201

IV Administration of Amphotericin B Liposomal (AmBisome)

Reconstitution and Dilution

Amphotericin B liposomal must be reconstituted prior to administration.

Reconstitute 50-mg vial by adding 12 mL of sterile water for injection to provide a solution containing 4 mg/mL.202 Other diluents (e.g., diluents containing sodium chloride or a bacteriostatic agent) should not be used to reconstitute amphotericin B liposomal, and reconstituted solutions should not be admixed with other drugs.202

Reconstituted solution should then be diluted by withdrawing the appropriate amount of solution into a sterile syringe.202 The 5-mcm sterile, disposable filter provided by the manufacturer should then be attached to the syringe and the syringe contents injected through the filter into the appropriate volume of 5% dextrose injection to provide a final concentration of 1–2 mg/mL.202 Lower concentrations (0.2–0.5 mg/mL) may be appropriate for infants and small children.202

May be infused through an in-line membrane filter provided the mean pore diameter of the filter is ≥1 mcm.202

May be administered through an existing IV line; the line must be flushed with 5% dextrose injection prior to infusion of the antifungal.202 If this is not feasible, amphotericin B liposomal must be administered through a separate line.202

Rate of Administration

Administer amphotericin B liposomal by IV infusion over a period of approximately 2 hours using a controlled infusion device.202 If the infusion is well tolerated, infusion time may be reduced to approximately 1 hour; duration of infusion should be increased in patients who experience discomfort during infusion.202

Dosage

Available as conventional amphotericin B (formulated with sodium desoxycholate),135 amphotericin B cholesteryl sulfate complex (Amphotec),203 amphotericin B lipid complex (Abelcet),201 or amphotericin B liposomal (AmBisome);202 dosage is expressed as amphotericin B.201 202 203 135

Dosage varies depending on whether the drug is administered as conventional amphotericin B or as amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal.201 202 203 135 Dosage recommendations for the specific formulation being administered should be followed.201 202 203 135

Prior to initiation of conventional IV amphotericin B therapy, a single test dose of the drug (1 mg in 20 mL of 5% dextrose injection) should be administered IV over 20–30 minutes and the patient carefully monitored (i.e., pulse and respiration rate, temperature, blood pressure) every 30 minutes for 2 hours.135 In patients with good cardiorenal function who tolerate the test dose, therapy may be initiated with a daily dosage of 0.25 mg/kg (0.3 mg/kg in those with severe or rapidly progressing fungal infections) given as a single daily dose.135 In patients with impaired cardiorenal function and in patients who have severe reactions to the test dose, therapy should be initiated with a smaller daily dosage (i.e., 5–10 mg).135 Depending on patient’s cardiorenal status, dosage may gradually be increased by 5–10 mg daily to a final daily dosage of 0.5–0.7 mg/kg.135

Pediatric Patients

General Pediatric Dosage
Treatment of Invasive Fungal Infections
IV

Conventional amphotericin B: AAP recommends 1–1.5 mg/kg once daily.146 Use lowest effective dosage.135 417

Amphotericin B cholesteryl sulfate complex: 3–4 mg/kg once daily.203

Amphotericin B lipid complex: 5 mg/kg once daily.146 201 235

Amphotericin B liposomal: 3–5 mg/kg daily.202

Aspergillosis
Treatment of Aspergillosis
IV

Conventional amphotericin B in HIV-infected infants and children: 1–1.5 mg/kg once daily for at least 12 weeks; duration based on clinical response.441

Conventional amphotericin B in HIV-infected adolescents: 1 mg/kg once daily continued at least until CD4+ T-cells are >200/mm3 in response to antiretroviral therapy and there is evidence of resolution of aspergillosis.440

Amphotericin B (a lipid formulation) in HIV-infected infants and children: 5 mg/kg once daily for at least 12 weeks; duration based on clinical response.441

Amphotericin B (a lipid formulation) in HIV-infected adolescents: 5 mg/kg once daily continued at least until CD4+ T-cells are >200/mm3 and there is evidence of clinical response.440

Amphotericin B cholesteryl sulfate complex: 3–4 mg/kg once daily.203

Amphotericin B lipid complex: 5 mg/kg once daily.201

Amphotericin B liposomal: 3–5 mg/kg once daily in children ≥1 month of age.202 231 232

Optimal duration of therapy for aspergillosis is uncertain.423 IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks and continued throughout the period of immunosuppression.423

Blastomycosis
Treatment of Severe Blastomycosis
IV

Conventional amphotericin B: IDSA recommends 0.7–1 mg/kg once daily, followed by oral itraconazole for a total treatment duration of 12 months.424

Amphotericin B (a lipid formulation): IDSA recommends 3–5 mg/kg once daily, followed by oral itraconazole for a total treatment duration of 12 months.424

Candida Infections
Treatment of Disseminated or Invasive Candida Infections
IV

Conventional amphotericin B: 0.5–1 mg/kg daily.146 254 436 Usual duration of treatment for candidemia is 2 weeks after documented clearance of Candida from the bloodstream, resolution of symptoms attributable to candidemia, and resolution of neutropenia.425

Amphotericin B lipid complex: 5 mg/kg once daily.201

Amphotericin B liposomal: 3–5 mg/kg once daily in children ≥1 month of age.202 231 232 Median duration has been 15–29 days;230 231 232 379 some Candida infections have been effectively treated with a median duration of 5–7 days.230 231 232

Treatment of Neonatal Candidiasis
IV

Conventional amphotericin B: 1 mg/kg daily for at least 3 weeks.425

Treatment of Severe or Refractory Oropharyngeal Candidiasis
IV

Conventional amphotericin B in HIV-infected adolescents: 0.3 mg/kg daily.440

Amphotericin B (a lipid formulation) in HIV-infected adolescents: 3–5 mg/kg daily.440

Treatment of Esophageal Candidiasis
IV

Conventional amphotericin B in HIV-infected adolescents: 0.6 mg/kg daily for 14–21 days.440

Amphotericin B (a lipid formulation) in HIV-infected adolescents: 3–4 mg/kg daily for 14–21 days.440

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
IV

Conventional amphotericin B in HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis: 0.5–1 mg/kg once daily.441

Conventional amphotericin B in HIV-infected adolescents with diffuse pulmonary or extrathoracic disseminated coccidioidomycosis: 0.7–1 mg/kg daily.440

Amphotericin B lipid complex in HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis: 5 mg/kg daily.441

Amphotericin B liposomal in HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis: 3–5 mg/kg daily.441

Amphotericin B (a lipid formulation) in HIV-infected adolescents with diffuse pulmonary or extrathoracic disseminated coccidioidomycosis: 4–6 mg/kg daily.440

Continue treatment with amphotericin B (conventional or lipid formulation) until improvement occurs, then switch to follow-up treatment with oral fluconazole or oral itraconazole.440 441 IDSA recommends a total treatment duration of at least 1 year.426 441

HIV-infected children and adolescents who have been adequately treated for coccidioidomycosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral itraconazole to prevent relapse or recurrence.440 441

Cryptococcosis
Treatment of Cryptococcosis (Nonmeningeal)
IV

Conventional amphotericin B in children with disseminated cryptococcosis: Induction therapy with 1 mg/kg daily given with oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole alone for at least 8 weeks.427

Conventional amphotericin B in HIV-infected infants and children with severe pulmonary or disseminated cryptococcosis: 0.7–1 mg/kg daily (with or without oral flucytosine).441 Same dosage can be used without flucytosine for localized disease (e.g., isolated pulmonary disease).441 Treatment duration depends on response and site and severity of infection.441

Amphotericin B lipid complex in HIV-infected infants and children with severe pulmonary or disseminated cryptococcosis: 5 mg/kg daily (with or without oral flucytosine).441 Same dosage can be used without flucytosine for localized disease (e.g., isolated pulmonary disease).441 Treatment duration depends on response and site and severity of infection.441

Amphotericin B liposomal in children ≥1 month of age: Manufacturer recommends 3–5 mg/kg once daily.202

Amphotericin B liposomal in HIV-infected infants and children with severe pulmonary or disseminated cryptococcosis: 3–5 mg/kg daily (with or without oral flucytosine).441 Same dosage can be used without flucytosine for localized disease (e.g., isolated pulmonary disease).441 Treatment duration depends on response and site and severity of infection.441

Treatment of Cryptococcal Meningitis
IV

Conventional amphotericin B in HIV-infected infants and children: Induction therapy with 0.7–1 mg/kg daily given with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.427 441

Conventional amphotericin B in HIV-infected infants and children who cannot receive flucytosine: Induction therapy with 0.7–1.5 mg/kg daily for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.441

Conventional amphotericin B in HIV-infected adolescents: Induction therapy with 0.7–1 mg/kg daily given in conjunction with oral flucytosine for at least 2 weeks and until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.440

Amphotericin B lipid complex in HIV-infected infants, children, and adolescents: Induction therapy with 5 mg/kg daily given with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.427 440 441

Amphotericin B liposomal in HIV-infected children ≥1 month of age: Manufacturer recommends 6 mg/kg once daily.202

Amphotericin B liposomal in HIV-infected infants and children: Induction therapy with 4–6 mg/kg daily given with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.427 441 Same dosage can be used in children who cannot receive flucytosine.441

Amphotericin B liposomal in HIV-infected adolescents: Induction therapy with 3–4 mg/kg daily given in conjunction with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.440

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
IV

HIV-infected children and adolescents who have been adequately treated for cryptococcosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole to prevent relapse or recurrence.427 440 441

Conventional amphotericin B in HIV-infected adolescents who cannot receive fluconazole: 1 mg/kg once weekly.427 Initiate secondary prophylaxis after the primary infection has been adequately treated.427

Some experts state consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adolescents who have received at least 1 year of chronic maintenance antifungal treatment, are asymptomatic for cryptococcosis, are receiving antiretroviral therapy, and have had CD4+ T-cells ≥100/mm3 for ≥3 months.440

If secondary prophylaxis against cryptococcosis is discontinued, follow patient closely and perform serial cryptococcal serum antigen tests.427 Reinitiate secondary prophylaxis if CD4+ T-cells decrease to <100/mm3 and/or serum cryptococcal antigen titer increases.427 440

Histoplasmosis
Treatment of Histoplasmosis
IV

Conventional amphotericin B for treatment of progressive disseminated histoplasmosis: IDSA recommends 1 mg/kg daily for 4–6 weeks or, alternatively, an initial regimen of 1 mg/kg daily given for 2–4 weeks then follow-up treatment with oral itraconazole for a total treatment duration of 3 months.428

Conventional amphotericin B for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected infants or children: CDC, NIH, and IDSA recommend initial regimen of 1 mg/kg once daily given for at least 1–2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.441

Conventional amphotericin B for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected adolescents: CDC, NIH, and IDSA recommend initial regimen of 0.7 mg/kg daily given for at least 2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440

Amphotericin B lipid complex for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected adolescents: CDC, NIH, and IDSA recommend initial regimen of 5 mg/kg daily given for at least 2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440

Amphotericin B liposomal for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected infants, children, and adolescents: CDC, NIH, and IDSA recommend initial regimen of 3 mg/kg once daily given for at least 1–2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440 441

Amphotericin B liposomal for treatment of CNS histoplasmosis in HIV-infected infants, children, and adolescents: CDC, NIH, and IDSA recommend initial regimen of 5 mg/kg once daily for 4–6 weeks and follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months and until abnormal CSF findings resolve and histoplasmal antigen is undetectable.440 441

HIV-infected children and adolescents and other immunosuppressed individuals who have been adequately treated for histoplasmosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole to prevent relapse or recurrence.428 440

Penicilliosis
Treatment of Penicilliosis
IV

Conventional amphotericin B in HIV-infected adolescents with severe penicilliosis: 0.6 mg/kg daily for 2 weeks, followed by oral itraconazole (400 mg daily) for 10 weeks.440

Sporotrichosis
Treatment of Sporotrichosis
IV

Conventional amphotericin B in children with disseminated sporotrichosis: Initial treatment with 0.7 mg/kg daily until a response is obtained, followed by oral itraconazole for a total treatment duration of at least 12 months.429

Leishmaniasis
Treatment of Cutaneous and Mucocutaneous Leishmaniasis
IV

Conventional amphotericin B: 0.25–0.5 mg/kg daily initially;102 103 104 105 109 gradually increase dosage until 0.5–1 mg/kg daily is reached,104 105 107 108 109 126 at which time the drug usually is given on alternate days.107 108 126 For mucosal disease, some clinicians recommend 0.5–1 mg/kg daily or every second day for up to 8 weeks.442

Duration of therapy depends on severity of disease and response to the drug, but generally is 3–12 weeks.102 103 105 Total treatment dose generally ranges from 1–3 g;102 105 106 107 108 109 mucocutaneous disease usually requires a higher total dose than cutaneous disease.102 103 109

Treatment of Visceral Leishmaniasis (Kala-Azar)
IV

Conventional amphotericin B: 0.5–1 mg/kg administered on alternate days for 14–20 doses has been used.126 256 257 Some clinicians recommend 1 mg/kg daily for 15–20 days or every second day for up to 8 weeks for a total treatment dose of 15–20 mg/kg.442

Amphotericin B liposomal in immunocompetent children ≥1 month of age: Manufacturer recommends 3 mg/kg once daily on days 1–5, then 3 mg/kg once daily on days 14 and 21;202 a second course of the drug may be useful if the infection is not completely cleared with a single course.202

Amphotericin B liposomal in immunocompromised children ≥1 month of age: Manufacturer recommends 4 mg/kg once daily on days 1–5, then 4 mg/kg daily on days 10, 17, 24, 31, and 38;202 if the parasitic infection is not completely cleared after the first course or if relapses occur, consult an expert regarding further treatment.202

Various other dosage regimens of amphotericin B liposomal have been used, including 10 mg/kg daily given on 2 consecutive days.444

Treatment of Cutaneous Leishmaniasis in HIV-infected Adolescents
IV

Amphotericin B lipid liposomal: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Treatment of Visceral Leishmaniasis (Kala-Azar) in HIV-infected Adolescents
IV

Conventional amphotericin B: 0.5–1 mg/kg daily for a total treatment dose of 1.5–2 g.440

Amphotericin B lipid complex: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Amphotericin B liposomal: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Prevention of Recurrence (Secondary Prophylaxis) of Visceral Leishmaniasis (Kala-Azar) in HIV-infected Adolescents
IV

Amphotericin B lipid complex: 3–4 mg/kg once every 2–4 weeks.440

Amphotericin B liposomal: 4 mg/kg once every 2–4 weeks.440

Initiate secondary prophylaxis after infection has been adequately treated.440

Consideration can be given to discontinuing secondary prophylaxis if CD4+ T-cells have remained >350/mm3 for ≥3–6 months.440 Some clinicians suggest that secondary prophylaxis against leishmaniasis be continued indefinitely in HIV-infected individuals.440

Primary Amebic Meningoencephalitis
Treatment of Naegleria Infections
IV and Intrathecal

Conventional amphotericin B: 1.5 mg/kg IV daily in 2 divided doses for 3 consecutive days, then 1 mg/kg IV daily for 6 consecutive days.442 Used in conjunction with amphotericin B given intrathecally in a dosage of 1.5 mg daily for 2 days, then 1 mg every other day for 8 days.442 Has been used alone or in conjunction with other anti-infectives.146 442

Adults

Aspergillosis
Treatment of Aspergillosis
IV

Conventional amphotericin B: 0.5–1.5 mg/kg daily.211 236 243 248 268 273 279 290 346 423 Total treatment dose up to 3.6 g has been given over an 11-month period.135 417

Conventional amphotericin B in HIV-infected adults: 1 mg/kg once daily continued at least until CD4+ T-cells are >200/mm3 in response to antiretroviral therapy and there is evidence of resolution of aspergillosis.440

Amphotericin B (a lipid formulation) in HIV-infected adults: 5 mg/kg once daily continued at least until CD4+ T-cells are >200/mm3 and there is evidence of clinical response.440

Amphotericin B cholesteryl sulfate complex: 3–4 mg/kg once daily.203

Amphotericin B lipid complex: 5 mg/kg once daily.201 423 Median duration has been 25 days.204

Amphotericin B liposomal: 3–5 mg/kg once daily.202 231 232 423 Higher dosage does not result in improved efficacy and is associated with an increased incidence of adverse effects (e.g., nephrotoxicity).423 459

Optimal duration of therapy for aspergillosis is uncertain.423 IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks and continued throughout the period of immunosuppression.423

Blastomycosis
Treatment of Blastomycosis
IV

Conventional amphotericin B: 0.5–1 mg/kg daily.211 436

Treatment of Moderately Severe to Severe Pulmonary Blastomycosis
IV

Conventional amphotericin B: 0.7–1 mg/kg once daily for 1–2 weeks or until improvement occurs, followed by oral itraconazole therapy for a total treatment duration of 6–12 months.424

Amphotericin B (a lipid formulation): 3–5 mg/kg once daily for 1–2 weeks or until improvement occurs, followed by oral itraconazole therapy for a total treatment duration of 6–12 months.424

Treatment of Disseminated Extrapulmonary Blastomycosis (Without CNS Involvement)
IV

Conventional amphotericin B: 0.7–1 mg/kg once daily for 1–2 weeks or until improvement occurs, followed by oral itraconazole therapy for a total treatment duration of at least 12 months.424

Amphotericin B (a lipid formulation): 3–5 mg/kg once daily for 1–2 weeks or until improvement occurs, followed by oral itraconazole therapy for a total treatment duration of at least 12 months.424

Treatment of CNS Blastomycosis
IV

Amphotericin B (a lipid formulation): 5 mg/kg once daily for 4–6 weeks, followed by oral azole therapy (fluconazole, itraconazole, voriconazole) for a total treatment duration of at least 12 months and until CSF abnormalities resolve.424

Candida Infections
Treatment of Disseminated or Invasive Candida Infections
IV

Conventional amphotericin B: 0.5–1 mg/kg daily.211 223 254 307 425 436 Usual duration of treatment for candidemia is 2 weeks after documented clearance of Candida from the bloodstream, resolution of symptoms attributable to candidemia, and resolution of neutropenia.425

Amphotericin B cholesteryl sulfate complex: 3–6 mg/kg once daily.219 220 Dosages up to 7.5 mg/kg have been used in BMT patients.250

Amphotericin B lipid complex: 5 mg/kg once daily.201

Amphotericin B liposomal: 3–5 mg/kg once daily.202 231 232 Median duration has been 15–29 days;230 231 232 379 some Candida infections were effectively treated with a median duration of 5–7 days.230 231 232

Treatment of Chronic Disseminated (Hepatosplenic) Candidiasis
IV

Conventional amphotericin B in severely ill patients: Initial regimen of 0.5–0.7 mg/kg daily for 1–2 weeks followed by fluconazole.425 Continue antifungal treatment until calcification occurs or lesions resolve (usually weeks to months); continue through periods of immunosuppression.425

Amphotericin B (a lipid formulation) in severely ill patients: Initial regimen of 3–5 mg/kg daily for 1–2 weeks followed by fluconazole.425 Continue antifungal treatment until calcification occurs or lesions resolve (usually weeks to months); continue through periods of immunosuppression.425

Treatment of CNS Candidiasis
IV

Amphotericin B (a lipid formulation): IDSA recommends an initial regimen of 3–5 mg/kg daily (with or without flucytosine) given for several weeks, then follow-up therapy with fluconazole.425 Continue antifungal treatment until signs and symptoms, CSF abnormalities, and radiologic abnormalities have resolved.425

Treatment of Severe or Refractory Oropharyngeal Candidiasis
IV

Conventional amphotericin B in HIV-infected or other adults: 0.3 mg/kg daily.425

Treatment of Esophageal Candidiasis
IV

Conventional amphotericin B in adults who cannot tolerate oral therapy: 0.3–0.7 mg/kg daily.425

Conventional amphotericin B in HIV-infected or other adults: 0.6 mg/kg daily for 14–21 days.425 440

Amphotericin B (a lipid formulation) in HIV-infected adults: 3–4 mg/kg daily for 14–21 days.440

Treatment of Symptomatic Cystitis, Pyelonephritis, or Fungus Balls
IV

Conventional amphotericin B: 0.3–0.6 mg/kg daily for 1–7 days for symptomatic cystitis.425 For treatment of pyelonephritis, 0.5–0.7 mg/kg daily (with or without oral flucytosine) given for 2 weeks.425 For treatment of fungus balls, 0.5–0.7 mg/kg daily (with or without oral flucytosine) continued until symptoms resolve and urine cultures are negative for Candida.425

Bladder Irrigation

Conventional amphotericin B bladder irrigation as an adjunct to systemic antifungal therapy for treatment of symptomatic cystitis or urinary fungus balls caused by fluconazole-resistant Candida (e.g., C. glabrata, C. krusei): 50-mg/L solution in sterile water.425 IDSA states that optimal dose and duration of bladder irrigation not established.425

Treatment of Candiduria
Bladder Irrigation

Conventional amphotericin B: Optimal concentration, method of bladder irrigation (continuous or intermittent), and duration not established.251 260 262 425 466 468 469 470 471 For continuous bladder irrigation, conventional amphotericin B for injection has been reconstituted with sterile water for injection to a concentration of 50 mg/L and administered at a rate of 42 mL/hour for up to 15 days.260 432 433 467 468 470 Some clinicians suggest a lower concentration (5–10 mg/L) may be acceptable.468 471

Treatment of Candida Endophthalmitis
IV

Conventional amphotericin B in patients with advancing lesions or lesions threatening the macula: 0.7–1 mg/kg daily given in conjunction with oral flucytosine.425 Duration of treatment is at least 4–6 weeks as determined by repeated examinations to verify resolution.425

Treatment of Candida Cardiovascular Infections
IV

Conventional amphotericin B in patients with endocarditis: 0.6–1 mg/kg daily (with or without oral flucytosine).425 If infection is caused by fluconazole-susceptible strains, consider changing to follow-up therapy with oral fluconazole after patient is clinically stable and Candida have been cleared from the bloodstream.425

Conventional amphotericin B in patients with pericarditis: 0.6–1 mg/kg daily.425 Consider switching to oral fluconazole after a response has been obtained and patient is clinically stable.425

Amphotericin B (a lipid formulation) in patients with endocarditis: 3–5 mg/kg daily (with or without oral flucytosine).425 If infection is caused by fluconazole-susceptible strains, consider changing to follow-up therapy with oral fluconazole after patient is clinically stable and Candida have been cleared from the bloodstream.425

Amphotericin B (a lipid formulation) in patients with pericarditis: 3–5 mg/kg daily.425 Consider switching to oral fluconazole after a response has been obtained and patient is clinically stable.425

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
IV

Conventional amphotericin B in adults with diffuse pneumonia or disseminated coccidioidomycosis: 0.5–1.5 mg/kg daily.211 245 426 436

Conventional amphotericin B in HIV-infected adults with diffuse pulmonary or extrathoracic disseminated coccidioidomycosis: 0.7–1 mg/kg daily.440

Amphotericin B (a lipid formulation) in HIV-infected adults with diffuse pulmonary or extrathoracic disseminated coccidioidomycosis: 4–6 mg/kg daily.440

Continue treatment with amphotericin B (conventional or lipid formulation) until improvement occurs,440 then switch to follow-up treatment with oral fluconazole or oral itraconazole.440 IDSA recommends a total treatment duration of at least 1 year.426

HIV-infected adults who have been adequately treated for coccidioidomycosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral itraconazole to prevent relapse or recurrence.440

Treatment of Coccidioidal Meningitis
Intrathecal

Conventional amphotericin B: 0.1–1.5 mg doses have been given daily or weekly.426 Use low dose initially; gradually increase dose until there is evidence of intolerance (e.g., severe vomiting, prostration, transient dose-related mental status changes).426 Has been used alone or in conjunction with systemic antifungal therapy.146 426

Consultation with an expert experienced in treating coccidioidal meningitis recommended.146 440

Cryptococcosis
Treatment of Cryptococcosis (Nonmeningeal)
IV

Conventional amphotericin B: 0.3–1 mg/kg daily (with or without oral flucytosine) has been used.126 182 211 217 228 436

Amphotericin B cholesteryl sulfate complex: 3–6 mg/kg once daily has been used.219 220 Dosages up to 7.5 mg/kg have been used in BMT patients.250

Amphotericin B lipid complex: Manufacturer recommends 5 mg/kg once daily.201

Amphotericin B liposomal: Manufacturer recommends 3–5 mg/kg once daily.202

Treatment of Cryptococcal Meningitis
IV

Conventional amphotericin B in HIV-infected adults: Induction therapy with 0.7–1 mg/kg daily and oral flucytosine given for at least 2 weeks and until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.427 440

Conventional amphotericin B in HIV-infected adults who cannot receive flucytosine: Induction therapy with 0.7–1 mg/kg daily and oral or IV fluconazole given for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral fluconazole alone for at least 8 weeks.440

Conventional amphotericin B in immunocompetent adults who do not have HIV infection and are not transplant recipients: Induction therapy with 0.7–1 mg/kg daily and oral flucytosine given for at least 4 weeks (6 weeks in those with neurologic complications), then consolidation therapy with oral fluconazole alone for 8 weeks.427 If patient is immunocompetent without uncontrolled, underlying disease and is at low risk for therapeutic failure, induction regimen can be given for only 2 weeks, followed by consolidation therapy with oral fluconazole for 8 weeks.427 In those who cannot receive flucytosine, induction therapy with 0.7–1 mg/kg daily alone for at least 6 weeks, then consolidation therapy with oral fluconazole alone for 8 weeks.427

Amphotericin B lipid complex: 5 mg/kg once daily for 6 weeks followed by 12 weeks of oral fluconazole.216 201

Amphotericin B lipid complex in HIV-infected adults: Induction therapy with 5 mg/kg daily and oral flucytosine given for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.440

Amphotericin B lipid complex in HIV-infected adults who cannot receive flucytosine and fluconazole: Induction and consolidation therapy in a dosage of 5 mg/kg daily for 4–6 weeks.427

Amphotericin B lipid complex in organ transplant recipients with CNS cryptococcosis: Induction therapy with 5 mg/kg daily and oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole alone for 8 weeks.427 If flucytosine cannot be used, consider continuing induction therapy for at least 4–6 weeks before initiating consolidation therapy.427

Amphotericin B lipid complex in immunocompetent adults who do not have HIV infection and are not transplant recipients: Induction therapy with 5 mg/kg daily and oral flucytosine given for at least 4 weeks (6 weeks in those with neurologic complications), then consolidation therapy with oral fluconazole alone for 8 weeks.427 If patient is immunocompetent without uncontrolled, underlying disease and is at low risk for therapeutic failure, induction regimen can be given for only 2 weeks, followed by consolidation therapy with oral fluconazole alone for 8 weeks.427 In those who cannot receive flucytosine, induction therapy with 5 mg/kg daily alone for at least 6 weeks, then consolidation therapy with oral fluconazole given for 8 weeks.427

Amphotericin B liposomal in HIV-infected adults: Manufacturer recommends 6 mg/kg once daily.202

Amphotericin B liposomal in HIV-infected adults: Induction therapy with 3–4 mg/kg daily and oral flucytosine given for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral or IV fluconazole alone for at least 8 weeks.440

Amphotericin B liposomal in HIV-infected adults who cannot receive flucytosine and fluconazole: Induction and consolidation therapy in a dosage of 3–6 mg/kg daily for 4–6 weeks.427

Amphotericin B liposomal in adult organ transplant recipients with CNS cryptococcosis: Induction therapy with 3–4 mg/kg daily and oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole alone for 8 weeks followed by a maintenance regimen of oral fluconazole given for 6–12 months.427 If flucytosine cannot be used in the induction regimen, consider continuing induction therapy for at least 4–6 weeks before initiating consolidation therapy.427 For relapse or high fungal burden, consider amphotericin B liposomal dosage of 6 mg/kg daily.427

Amphotericin B liposomal in immunocompetent adults who do not have HIV infection and are not transplant recipients: Induction therapy with 3–4 mg/kg daily and oral flucytosine given for at least 4 weeks (6 weeks in those with neurologic complications), then consolidation therapy with oral fluconazole alone for 8 weeks.427 If patient is immunocompetent without uncontrolled, underlying disease and is at low risk for therapeutic failure, induction regimen can be given for only 2 weeks, followed by consolidation therapy with oral fluconazole alone for 8 weeks.427 In those who cannot receive flucytosine, induction therapy with 3–4 mg/kg daily alone for at least 6 weeks, then consolidation therapy with oral fluconazole alone for 8 weeks.427

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
IV

Conventional amphotericin B in HIV-infected adults who cannot receive fluconazole: 1 mg/kg once weekly.427 Initiate secondary prophylaxis after the primary infection has been adequately treated.427

IDSA states consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adults who have received at least 1 year of antifungal treatment, are receiving antiretroviral therapy, have had undetectable or low plasma HIV RNA levels for at least 3 months, and have CD4+ T-cells >100/mm3.427

Other experts state consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adults who have received at least 1 year of chronic maintenance antifungal treatment, are asymptomatic for cryptococcosis, are receiving antiretroviral therapy, and have had CD4+ T-cells ≥100/mm3 for ≥3 months.440

If secondary prophylaxis against cryptococcosis is discontinued, follow patient closely and perform serial cryptococcal serum antigen tests.427 Reinitiate secondary prophylaxis if CD4+ T-cells decrease to <100/mm3 and/or serum cryptococcal antigen titer increases.427 440

Exserohilum Infections
Treatment of Known or Suspected Exserohilum Infections
IV

Amphotericin B liposomal for treatment of CNS and/or parameningeal infections: CDC recommends 5–6 mg/kg daily.484 Higher dosage (7.5 mg/kg daily) may be considered if patient is not improving, but risk of nephrotoxicity is increased.484 Consider giving 1 L of 0.9% sodium chloride injection prior to IV infusion of amphotericin B liposomal to minimize risk of nephrotoxicity.484

Amphotericin B liposomal or other lipid formulation for treatment of osteoarticular infections: CDC recommends 5 mg/kg daily.485

Adequate duration of antifungal treatment unknown; prolonged treatment required based on disease severity and clinical response.484

In those with severe CNS disease with complications (arachnoiditis, stroke), persistent CSF abnormalities, or underlying immunosuppression, treatment duration of 6–12 months probably necessary.484 In those with parameningeal infection, consider minimum duration of 3–6 months (≥6 months for more severe disease such as discitis or osteomyelitis, underlying immunosuppression, or complications not amenable to surgical treatment).484

In those with osteoarticular infections, consider minimum duration of 3 months (>3 months probably necessary for severe disease, bone infections, or underlying immunosuppression).485

After treatment completion, close follow-up monitoring essential in all patients to detect potential relapse.484 485

Consult infectious disease expert and most recent CDC guidelines for information regarding management.477 484 485 Consult CDC website at for most recent recommendations regarding drugs of choice, dosage, and duration of treatment.477 484 485

Histoplasmosis
Treatment of Histoplasmosis
IV

Conventional amphotericin B for treatment of moderately severe to severe acute pulmonary histoplasmosis or progressive disseminated histoplasmosis: IDSA recommends initial regimen of 0.7–1 mg/kg daily for 1–2 weeks, followed by oral itraconazole for a total duration of 12 weeks for acute pulmonary disease or at least 12 months for progressive disseminated disease.428

Conventional amphotericin B for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected adults: CDC, NIH, and IDSA recommend initial (induction) regimen of 0.7 mg/kg daily given for at least 2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440

Amphotericin B lipid complex for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected adults: CDC, NIH, and IDSA recommend initial regimen of 5 mg/kg daily given for at least 2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440

Amphotericin B liposomal for treatment of moderately severe to severe acute pulmonary histoplasmosis: IDSA recommends initial regimen of 3–5 mg/kg daily for 1–2 weeks, followed by oral itraconazole for a total duration of 12 weeks.428 For treatment of moderately severe to severe progressive disseminated histoplasmosis, IDSA recommends an initial regimen of 3 mg/kg daily for 1–2 weeks, followed by oral itraconazole for a total duration of at least 12 months.428

Amphotericin B liposomal for treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected adults: CDC, NIH, and IDSA recommend initial regimen of 3 mg/kg once daily given for at least 2 weeks or until a response is obtained, then follow-up treatment with oral itraconazole for a total treatment duration of at least 12 months.440

Amphotericin B liposomal for treatment of CNS histoplasmosis in HIV-infected adults or other adults: CDC, NIH, and IDSA recommend an initial regimen of 5 mg/kg once daily for 4–6 weeks and follow-up treatment with oral itraconazole given for a total treatment duration of at least 12 months and until abnormal CSF findings resolve and histoplasmal antigen is undetectable.428 440

HIV-infected adults and other immunosuppressed individuals who have been adequately treated for histoplasmosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole to prevent relapse or recurrence.428 440

Paracoccidioidomycosis
Treatment of Paracoccidioidomycosis
IV

Conventional amphotericin B: 0.4–0.5 mg/kg daily, although higher dosage (i.e., 1 mg/kg daily or, rarely, 1.5 mg/kg daily) has been used for treatment of rapidly progressing, potentially fatal infections.221 Prolonged therapy usually required.221 In severely ill patients, 0.7–1 mg/kg daily for initial treatment followed by oral itraconazole recommended.436

Penicilliosis
Treatment of Penicilliosis
IV

Amphotericin B liposomal in HIV-infected adults with severe penicilliosis: 3–5 mg/kg daily given for 2 weeks, followed by oral itraconazole (200 mg twice daily) for 10 weeks.440

Sporotrichosis
Treatment of Sporotrichosis
IV

Conventional amphotericin B: Manufacturers state the drug has been given for up to 9 months to provide a total treatment dose of up to 2.5 g.135 417

Conventional amphotericin B in patients with osteoarticular sporotrichosis: 0.7–1 mg/kg daily or until a response is obtained, followed by oral itraconazole for a total treatment duration of at least 12 months.429

Conventional amphotericin B in patients with severe or life-threatening pulmonary or disseminated sporotrichosis: 0.7–1 mg/kg daily can be used for initial therapy, but a lipid formulation is preferred for disseminated infections.429

Conventional amphotericin B in patients with meningeal sporotrichosis: 0.7–1 mg/kg daily can be used for initial therapy, but a lipid formulation is preferred.429

Amphotericin B (a lipid formulation) in patients with osteoarticular sporotrichosis: 3–5 mg/kg daily or until a response is obtained, followed by oral itraconazole for a total treatment duration of at least 12 months.429

Amphotericin B (a lipid formulation) in patients with severe or life-threatening pulmonary or disseminated sporotrichosis: 3–5 mg/kg daily until a response is obtained, followed by oral itraconazole for a total treatment duration of at least 12 months.429

Amphotericin B (a lipid formulation) in patients with meningeal sporotrichosis: 5 mg/kg daily for at least 4–6 weeks, followed by oral itraconazole for a total treatment duration of at least 12 months.429

Zygomycosis
Treatment of Zygomycosis
IV

Conventional amphotericin B: 1–1.5 mg/kg daily for 2–3 months.126 211 248 A total treatment dose of 3–4 g recommended for treatment of rhinocerebral phycomycosis; concomitant therapy has included irrigation of the sinus cavities with a suspension of 1 mg/mL.135

Amphotericin B lipid complex: 5 mg/kg once daily.201

Empiric Therapy in Febrile Neutropenic Patients
IV

Conventional amphotericin B: 0.5–1 mg/kg daily has been used.452

Amphotericin B cholesteryl sulfate complex: 4 mg/kg daily for a median duration of 8 days has been used.344

Amphotericin B lipid complex: 3–5 mg/kg daily has been used.452

Amphotericin B liposomal: 3 mg/kg once daily.202

Discontinue when neutropenia resolves.422 In those with prolonged neutropenia, IDSA suggests that empiric antifungal therapy may be discontinued after 2 weeks if patient is clinically well and no discernible lesions are found by clinical evaluation, chest radiographs, or abdominal CT scans.422 If patient appears ill or is at high risk, consider continuing empiric antifungal treatment throughout the neutropenic episode.422

Prevention of Fungal Infections in Transplant Recipients, Cancer Patients, or Other Patients at High Risk
IV

Conventional amphotericin B in neutropenic cancer patients or patients undergoing BMT: 0.1–0.25 mg/kg daily.126 249 277 287 375

Conventional amphotericin B in high-risk patients undergoing urologic procedures: 0.3–0.6 mg/kg daily for several days before and after the procedure.425

Amphotericin B liposomal for postoperative prophylaxis in liver, pancreas, or small bowel transplant recipients: 1–2 mg/kg daily for at least 7–14 days.425

Amphotericin B liposomal in neutropenic patients: 2 mg/kg 3 times weekly has been used.358

Leishmaniasis
Treatment of Cutaneous and Mucocutaneous Leishmaniasis
IV

Conventional amphotericin B: 0.25–0.5 mg/kg daily initially;102 103 104 105 109 gradually increase dosage until 0.5–1 mg/kg daily is reached,104 105 107 108 109 126 at which time the drug usually is given on alternate days.107 108 126 For mucosal disease, some clinicians recommend 0.5–1 mg/kg daily or every second day for up to 8 weeks.442

Duration depends on the severity of disease and response to the drug, but generally is 3–12 weeks.102 103 105 442 Total treatment dose generally ranges from 1–3 g;102 105 106 107 108 109 mucocutaneous disease usually requires a higher total dose than cutaneous disease.102 103 109

Treatment of Cutaneous Leishmaniasis in HIV-infected Adults
IV

Amphotericin B liposomal: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Treatment of Visceral Leishmaniasis (Kala-Azar)
IV

Conventional amphotericin B: 0.5–1 mg/kg administered on alternate days for 14–20 doses has been used.126 256 257 Some clinicians recommend 1 mg/kg daily for 15–20 days or 1 mg/kg every second day for up to 8 weeks for a total treatment dose of 15–20 mg/kg.442

Amphotericin B cholesteryl sulfate complex: 2 mg/kg once daily for 7–10 days.259

Amphotericin B lipid complex: 1–3 mg/kg once daily for 5 days has been used in patients who failed to respond to or relapsed after treatment with an antimony compound.246

Amphotericin B liposomal in immunocompetent adults: Manufacturer recommends 3 mg/kg once daily on days 1–5, then 3 mg/kg once daily on days 14 and 21;202 a second course of the drug may be useful if the infection is not completely cleared with a single course.202

Amphotericin B liposomal in immunocompromised adults: Manufacturer recommends 4 mg/kg once daily on days 1–5, then 4 mg/kg once daily on days 10, 17, 24, 31, and 38;202 if the parasitic infection is not completely cleared after the first course or if relapses occur, consult an expert regarding further treatment.202

Various other dosage regimens of amphotericin B liposomal have been used, including a single dose of 5–7.5 mg/kg or 10 mg/kg daily given on 2 consecutive days.443 444

Treatment of Visceral Leishmaniasis (Kala-Azar) in HIV-infected Adults
IV

Conventional amphotericin B: 0.5–1 mg/kg daily for a total treatment dose of 1.5–2 g.440

Amphotericin B lipid complex: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Amphotericin B liposomal: 2–4 mg/kg daily for 10 days or, alternatively, 4 mg/kg daily on days 1–5, 10, 17, 24, 31, and 38 for a total treatment dose of 20–60 mg/kg.440

Prevention of Recurrence (Secondary Prophylaxis) of Visceral Leishmaniasis (Kala-Azar) in HIV-infected Adults
IV

Amphotericin B lipid complex: 3 mg/kg once every 21 days.440

Amphotericin B liposomal: 4 mg/kg once every 2–4 weeks.440

Initiate secondary prophylaxis after infection has been adequately treated if CD4+ T-cells <200/mm3.440

Consideration can be given to discontinuing secondary prophylaxis if CD4+ T-cells have remained >200–350/mm3 for ≥3–6 months.440 Some clinicians suggest continuing secondary prophylaxis against leishmaniasis indefinitely in HIV-infected individuals.440

Primary Amebic Meningoencephalitis
Treatment of Naegleria Infections
IV and Intrathecal

Conventional amphotericin B: 1.5 mg/kg IV daily in 2 divided doses for 3 consecutive days, then 1 mg/kg IV daily for 6 consecutive days.442 Used in conjunction with amphotericin B given intrathecally in a dosage of 1.5 mg daily for 2 days, then 1 mg every other day for 8 days.442 Has been used alone or in conjunction with other anti-infectives.146 442

Prescribing Limits

Pediatric Patients

IV

Conventional amphotericin B: Use lowest effective dose.135

Adults

IV

Conventional amphotericin B: Daily dosage should not exceed 1.5 mg/kg.135

Cautions for Amphotericin B

Contraindications

  • Conventional amphotericin B, amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, and amphotericin B liposomal contraindicated in patients hypersensitive to amphotericin B or any component in the formulations.135 201 202 203

Warnings/Precautions

Warnings

Acute Infusion Reactions

Acute infusion reactions (fever, shaking, chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, tachypnea) may occur 1–3 hours after initiation of IV infusions of amphotericin B.135 201 202 203 207 211 264 341

Initial doses of conventional IV amphotericin B,135 amphotericin B cholesteryl sulfate complex,203 amphotericin B lipid complex,201 or amphotericin B liposomal202 should be administered under close clinical observation by medically trained personnel.

Infusion reactions reported most frequently with conventional amphotericin B, but also reported with amphotericin B cholesteryl sulfate,203 amphotericin B lipid complex,201 207 and amphotericin B liposomal.202 Reactions are most severe and occur most frequently with initial doses; usually lessen with subsequent doses.135 203 264 341

Up to 90% of patients receiving conventional IV amphotericin exhibit some degree of intolerance to initial doses of the drug, even when therapy is initiated with low doses.135 211 264 Although these reactions become less frequent following subsequent doses or administration of the drug on alternate days, they recur if conventional IV amphotericin B therapy is interrupted and then reinstituted.135

In patients receiving conventional amphotericin B, use of a test dose has been recommended.135 Use of a test dose also has been recommend each time a new course of amphotericin B cholesteryl sulfate complex is administered.203 (See Dosage and Administration.)

A premedication regimen (e.g., acetaminophen and diphenhydramine; acetaminophen, corticosteroid, and diphenhydramine) is not routinely recommended prior to initial doses of any amphotericin B formulation, but can be administered promptly to treat a reaction if it occurs and then as pretreatment prior to subsequent doses.341 346

Sensitivity Reactions

Hypersensitivity Reactions

Severe hypersensitivity reactions, including anaphylaxis, reported.201 202 203

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).201 202 203

Because amphotericin B may be the only effective treatment available for potentially life-threatening fungal infections, use of the drug might be considered in patients with hypersensitivity if the clinician determines that the benefits of such therapy outweigh the risks.201 202 203 Some manufacturers state that in such situations the drug is contraindicated in those who have had severe respiratory distress or a severe anaphylactic reaction.201 202 203

General Precautions

Laboratory Monitoring

Renal, hepatic, and hematologic function should be monitored in patients receiving conventional IV amphotericin B, amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal.135 201 202 203

Serum electrolytes (especially potassium and magnesium) and CBCs should be monitored.135 201 202 203

Specific Populations

Pregnancy

Category B.201 202 203

Lactation

Not known whether distributed into milk.201 202 203 Discontinue nursing or the drug.201 202 203

Pediatric Use

Conventional amphotericin B: Safety and efficacy not established by adequate and well-controlled studies, but the drug has been used effectively to treat systemic fungal infections in pediatric patients without unusual adverse effects.135 Use lowest effective dosage.135

Amphotericin B cholesteryl sulfate complex: No unusual adverse effects reported to date in pediatric patients who received dosages similar to those used in adults.203

Amphotericin B lipid complex: Generally well tolerated in pediatric patients; has been used for treatment of invasive fungal infections in children 3 weeks to 16 years of age without unusual adverse effects.201 398 Acute infusion reactions (fever, chills, rigors) and anaphylaxis have been reported in pediatric patients and have necessitated discontinuance of the drug.398

Amphotericin B liposomal: Has been administered to pediatric patients 1 month to 16 years of age without unusual adverse effects.202 247 404 Safety and efficacy not established in neonates <1 month of age.202 Has been used in a limited number of neonates for treatment of severe fungal infections without unusual adverse effects.401 403

Geriatric Use

No substantial differences in safety and efficacy of conventional IV amphotericin B,135 amphotericin B cholesteryl sulfate complex,203 amphotericin B lipid complex,201 or amphotericin B liposomal202 in patients ≥65 years of age.

Although dosage modifications usually unnecessary, carefully monitor during treatment.202

Renal Impairment

Conventional amphotericin B can be nephrotoxic and should be used with caution in patients with reduced renal function135

Lipid formulations (amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposomal) appear to be associated with a lower risk of nephrotoxicity than conventional IV amphotericin B and have been used in patients with preexisting renal impairment (in most cases resulting from prior therapy with conventional IV amphotericin B).201 202 203 207 216 219 244 265 333

Common Adverse Effects

Acute infusion reactions (fever, chills, headache, nausea, vomiting); nephrotoxicity; hematologic effects.135 201 202 203 207 216 219 244 264 265 333 Incidence may be lower with lipid formulations (amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposomal) than with conventional amphotericin B.201 202 203 207 216 219 244 265 333

Interactions for Amphotericin B

Systematic drug interaction studies have not been performed to date using amphotericin B cholesteryl sulfate complex,203 amphotericin B lipid complex,201 or amphotericin B liposomal.202 Consider that drug interactions reported with conventional IV amphotericin B could also occur with these lipid formulations of the drug.201 202 203

Nephrotoxic Drugs

Concurrent or sequential use with other nephrotoxic drugs (e.g., aminoglycosides, capreomycin, colistin, cisplatin, cyclosporine, methoxyflurane, pentamidine, polymyxin B, vancomycin) may result in additive nephrotoxic effects and should be avoided, if possible.135 201 202 203 417 Monitor renal function intensely if any amphotericin B formulation is used concomitantly with a nephrotoxic agent.135 201 202 203

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents (mechlorethamine)

May enhance potential for renal toxicity, bronchospasm, or hypotension135 201 202 203

Use concomitantly with caution135 201 202 203

Azole antifungals (ketoconazole, fluconazole, itraconazole)

In vitro evidence of antagonism against Candida or Aspergillus fumigatus202 203 312 336

Clinical importance unclear.203

Use concomitantly with caution, particularly in immunocompromised patients.135 202 336

Cardiac glycosides

Amphotericin B-induced hypokalemia may potentiate toxicity of cardiac glycosides135 202 203

If used concomitantly, closely monitor serum potassium concentrations and cardiac function135 202 203

Corticosteroids

Possible enhanced potassium depletion 135 202 203

Do not use concomitantly unless necessary to control adverse reactions to amphotericin B.135

If corticosteroids used concomitantly with any amphotericin B formulation, closely monitor serum electrolytes and cardiac function.135 201 202 203

Flucytosine

In vitro evidence of synergistic antifungal activity against Candida or Cryptococcus neoformans.b

Possibility of increased risk of flucytosine toxicity with conventional amphotericin B; may occur as the result of increased cellular uptake and/or decreased renal excretion of flucytosine.135 202 203

Use with caution and closely monitor flucytosine concentrations and CBCs169 182 197 203 346

Consider initiating flucytosine with a low dosage (75–100 mg/kg daily) and adjust subsequent dosage based on serum concentrations.126 346 436

Leukocyte transfusions

Administration of conventional amphotericin B during or shortly after leukocyte transfusions has been associated with acute pulmonary reactions135 199 202

Use amphotericin B with caution in patients receiving leukocyte transfusions, especially those with gram-negative septicemia.199

Amphotericin B doses should be separated in time as much as possible from leukocyte transfusions and pulmonary function monitored in patients receiving both therapies.135

Rifabutin

In vitro evidence of additive or synergistic antifungal activity against Aspergillus and Fusarium364

Skeletal muscle relaxants (tubocurarine)

Amphotericin B-induced hypokalemia may enhance curariform effects of skeletal muscle relaxants135 202 203

If used concomitantly, closely monitor serum potassium concentrations135 202 203

Zidovudine

Concomitant use in animals resulted in increased incidence of myelotoxicity and nephrotoxicity201

Clinical importance unclear; closely monitor renal and hematologic function if used concomitantly201

Amphotericin B Pharmacokinetics

The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B, amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal.135 201 202 203 205 210 332 Pharmacokinetic parameters reported for one formulation should not be used to predict pharmacokinetics of any other formulation.135 201 202 203 205 210 332

Absorption

Bioavailability

Amphotericin B is poorly absorbed from the GI tract and must be given parenterally.b

In general, usual dosages of amphotericin B cholesteryl sulfate complex203 208 210 338 or amphotericin B lipid complex201 206 207 210 265 333 result in lower serum concentrations and greater volumes of distribution than those reported for conventional amphotericin B.

Plasma concentrations attained with amphotericin B liposomal generally are higher and the volume of distribution is lower than those reported for conventional amphotericin B.202 205 209 210 269 332

Distribution

Extent

Information on distribution of amphotericin B is limited; distribution appears to be multicompartmental.b

To achieve fungistatic CSF concentrations, conventional amphotericin B must usually be administered intrathecally.b

Crosses the placenta.135 Not known whether distributed into milk.201 202 203

Plasma Protein Binding

>90% bound to plasma proteins, mainly lipoproteins.135

Elimination

Metabolism

Metabolic fate has not been fully elucidated.b

Elimination Route

Conventional amphotericin B is eliminated very slowly by the kidneys.135

Half-life

Conventional amphotericin B: Following IV administration, initial plasma half-life is approximately 24 hours.135 After the first 24 hours, the rate at which amphotericin B is eliminated decreases and an elimination half-life of approximately 15 days has been reported.135

Amphotericin B cholesteryl sulfate complex: Distribution half-life of 3.5 minutes and elimination half-life of 27.5–28.2 hours.203

Amphotericin B lipid complex: Terminal elimination half-life is 173 hours.201

Amphotericin B liposomal: Mean terminal elimination half-life is 100–153 hours.202

Special Populations

Amphotericin B cholesteryl sulfate complex: Pharmacokinetics not affected by hepatic impairment or renal impairment (Clcr ≥35 ml/minute); not evaluated in those with more severe hepatic or renal impairment.203

Stability

Storage

Parenteral

Powder for IV Infusion

Conventional amphotericin B: 2–8°C.135 417 Reconstituted colloidal dispersions should be protected from light and are stable for 24 hours at room temperature or 1 week when refrigerated at 2–8°C.135 417

Amphotericin B cholesteryl sulfate complex (Amphotec): 15–30°C.203 Following reconstitution with sterile water for injection, the colloidal dispersion should be refrigerated at 2–8°C and used within 24 hours; do not freeze.203 Reconstituted amphotericin B cholesteryl sulfate complex that has been further diluted in 5% dextrose injection should be stored at 2–8°C and used within 24 hours; any partially used vials should be discarded.203

Amphotericin B liposomal (AmBisome): 2–8°C.202 Following reconstitution with sterile water for injection, solutions containing 4 mg/mL may be stored for up to 24 hours at 2–8°C; do not freeze.202 IV infusions should be initiated within 6 hours after dilution in 5% dextrose injection;202 any partially used vials should be discarded.202

Suspension Concentrate for IV Infusion

Amphotericin B lipid complex (Abelcet): 2–8°C; protect from light.201 Following dilution in 5% dextrose injection, stable for up to 48 hours at 2–8°C and for an additional 6 hours at room temperature.201 Do not freeze; any unused solutions should be discarded.201

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Conventional Amphotericin B)HID

Compatible

Dextrose 5, 10, or 20% in water

Incompatible

Amino acids 4.25%, dextrose 25%

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.9%

Fat emulsion 10 and 20%, IV

Fat emulsion 20%, IV

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility (Conventional Amphotericin B)
Admixture CompatibilityHID

Compatible

Fluconazole

Heparin sodium

Hydrocortisone sodium succinate

Sodium bicarbonate

Incompatible

Amikacin sulfate

Calcium chloride

Calcium gluconate

Chlorpromazine HCl

Ciprofloxacin

Diphenhydramine HCl

Dopamine HCl

Edetate calcium disodium

Gentamicin sulfate

Magnesium sulfate

Meropenem

Methyldopate HCl

Penicillin G potassium

Penicillin G sodium

Polymyxin B sulfate

Potassium chloride

Prochlorperazine mesylate

Ranitidine HCl

Streptomycin sulfate

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Aldesleukin

Amiodarone HCl

Diltiazem HCl

Tacrolimus

Teniposide

Thiotepa

Zidovudine

Incompatible

Allopurinol sodium

Amifostine

Anidulafungin

Aztreonam

Bivalirudin

Caspofungin acetate

Ceftaroline fosamil

Dexmedetomidine HCl

Docetaxel

Doxorubicin HCl liposome injection

Enalaprilat

Etoposide phosphate

Fenoldopam mesylate

Filgrastim

Fluconazole

Fludarabine phosphate

Foscarnet sodium

Gemcitabine HCl

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Linezolid

Melphalan HCl

Meropenem

Ondansetron HCl

Paclitaxel

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Propofol

Telavancin HCl

Tigecycline

Vinorelbine tartrate

Variable

Cisatracurium besylate

Doripenem

Remifentanil HCl

Sargramostim

Solution Compatibility (Cholesteryl Sulfate)HID

Compatible

Dextrose 5% in water

Incompatible

Sodium chloride 0.9%

Drug Compatibility (Cholesteryl Sulfate)
Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Aminophylline

Cefoxitin sodium

Clindamycin phosphate

Co-trimoxazole

Cytarabine

Dexamethasone sodium phosphate

Fentanyl citrate

Furosemide

Ganciclovir sodium

Granisetron HCl

Hydrocortisone sodium succinate

Ifosfamide

Lorazepam

Mannitol

Methotrexate sodium

Methylprednisolone sodium succinate

Nitroglycerin

Sufentanil citrate

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Alfentanil HCl

Amikacin sulfate

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Aztreonam

Buprenorphine HCl

Butorphanol tartrate

Calcium chloride

Calcium gluconate

Carboplatin

Cefazolin sodium

Cefepime HCl

Ceftazidime

Ceftriaxone sodium

Chlorpromazine HCl

Cisatracurium besylate

Cisplatin

Cyclophosphamide

Cyclosporine

Diazepam

Digoxin

Diphenhydramine HCl

Dobutamine HCl

Dopamine HCl

Doxorubicin HCl

Doxorubicin HCl liposome injection

Droperidol

Enalaprilat

Esmolol HCl

Famotidine

Fluconazole

Fluorouracil

Gentamicin sulfate

Haloperidol lactate

Heparin sodium

Hydromorphone HCl

Hydroxyzine HCl

Imipenem–cilastatin sodium

Labetalol HCl

Leucovorin calcium

Lidocaine HCl

Magnesium sulfate

Meperidine HCl

Mesna

Metoclopramide HCl

Metoprolol tartrate

Metronidazole

Midazolam HCl

Mitoxantrone HCl

Morphine sulfate

Nalbuphine HCl

Naloxone HCl

Ondansetron HCl

Paclitaxel

Pentobarbital sodium

Phenobarbital sodium

Phenytoin sodium

Piperacillin sodium–tazobactam sodium

Potassium chloride

Prochlorperazine edisylate

Promethazine HCl

Propranolol HCl

Ranitidine HCl

Remifentanil HCl

Sodium bicarbonate

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Verapamil HCl

Vinorelbine tartrate

Variable

Doripenem

Solution Compatibility (Lipid Complex)HID

Compatible

Dextrose 5% in water

Drug Compatibility (Lipid Complex)
Y-Site CompatibilityHID

Compatible

Anidulafungin

Telavancin HCl

Incompatible

Caspofungin acetate

Tigecycline

Variable

Doripenem

Solution Compatibility (Liposomal)HID

Compatible

Dextrose 5% in water

Drug Compatibility (Liposomal)
Y-Site CompatibilityHID

Compatible

Anidulafungin

Incompatible

Caspofungin acetate

Telavancin HCl

Variable

Doripenem

Actions and Spectrum

  • Usually fungistatic in action at concentrations obtained clinically, but may be fungicidal in high concentrations or against very susceptible organisms.135 308 313

  • Binds to sterols (e.g., ergosterol) in cell membranes of susceptible fungi.135 201 202 203 269 As a result, cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs.135 203 Cell death occurs in part as a result of permeability changes;135 203 in some fungi, other mechanisms also may be involved.141 326 327 346

  • Active against most pathogenic fungi, including yeasts, and also active against some protozoa.135 312 315 339 Inactive against bacteria, rickettsiae, and most viruses.b

  • Candida: Active in vitro against most Candida,312 385 388 389 391 including C. albicans,385 388 391 C. dubliniensis,389 C. glabrata,385 391 C. krusei,385 C. parapsilosis,385 391 and C. tropicalis.385 391 389 391 May be active against some strains of C. lusitaniae,386 but other strains are resistant.343 399 402

  • Other fungi: Active against Aspergillus fumigatus,392 A. flavus,392 Blastomyces dermatitidis,b Coccidioides immitis,b C. posadasii,446 447 Cryptococcus neoformans,385 391 C. gattii,453 Exophiala castellanii,258 E. spinifera,258 Histoplasma capsulatum,b Paracoccidioides brasiliensis,b Rhodotorula,b and Sporothrix schenckii.b Active in vitro against Exserohilum rostratum.480 481 482 477 Some strains of Fusarium and Penicillium marneffei are inhibited in vitro by amphotericin B.409 445

  • Zygomycetes: Active against Absidia,418 419 Mucor,135 418 419 Rhizopus,418 419 Rhizomucor,418 419 Apophysomyces elegans,368 418 419 and Cunninghamella.418 419 Also active against Conidiobolus coronatus421 and some Basidiobolus, including B. ranarum,415 419 421 but resistance also reported.414 415

  • Protozoa: Active in vitro102 and in vivo102 103 104 105 106 107 108 109 against Leishmania braziliensis, L. mexicana,107 108 109 111 112 113 114 L. donovani,108 111 112 113 114 115 116 117 and L. tropica.111 114 Active against antimony-resistant Leishmania.107 108 109 111 112 113 114 115 116 117 Also active in vitro118 119 120 121 124 125 and possibly in vivo118 119 122 123 124 against Naegleria, particularly N. fowleri. Only limited and variable activity against Acanthamoeba castellanii and A. polyphaga.121 125

  • Fungi resistant to conventional amphotericin B also may be resistant to amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, and amphotericin B liposomal.201 202 203

Advice to Patients

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Amphotericin B

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

50 mg*

Amphotericin B for Injection

Amphotericin B Cholesteryl Sulfate Complex

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

50 mg (of amphotericin B)

Amphotec

Kadmon

100 mg (of amphotericin B)

Amphotec

Kadmon

Amphotericin B Lipid Complex

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension concentrate, for IV infusion

5 mg (of amphotericin B) per mL (100 mg)

Abelcet (formulated as a 1:1 molar ratio of amphotericin B to lipid complex; lipid complex composed of L-α-dimyristoylphosphatidylcholine [DMPC] 3.4 mg and L-α-dimyristoylphosphatidylglycerol [DMPG] 1.5 mg; with 5-mcm filter needle)

Enzon

Amphotericin B Liposomal

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

50 mg (of amphotericin B)

AmBisome (formulated in liposomes composed of hydrogenated soy, phosphatidylcholine [HSPC] 213 mg, cholesterol 52 mg, distearoylphosphatidylglycerol 84 mg, and α tocopherol 0.64 mg; with 5-mcm filter)

Astellas, (also promoted by Gilead Sciences)

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 18, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

57. Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007; 20:695-704. [PubMed 17934079]

100. Peterson LR, Hall WH, Kelty RH et al. Therapy of Candida peritonitis: penetration of amphotericin B into peritoneal fluid. Postgrad Med J. 1978; 54:340-2. [PubMed 673990]

101. Heidemann HT, Gerkens JF, Spickard WA et al. Amphotericin B nephrotoxicity in humans decreased by salt repletion. Am J Med. 1983; 75:476-81. [IDIS 175278] [PubMed 6614033]

102. Furtado TA. Clinical results in the treatment of American leishmaniasis with oral and intravenous amphotericin. Antibiot Annu. 1959-1960:631-7.

103. Sampaio SAP, Godoy JT, Paiva L et al. The treatment of American (mucocutaneous) leishmaniasis with amphotericin B. Arch Dermatol. 1960; 82:627-35. [PubMed 13745957]

104. Sampaio SAP, Castro RM, Dillon NL et al. Treatment of mucocutaneous (American) leishmaniasis with amphotericin B: report of 70 cases. Int J Dermatol. 1971; 10:179-81. [PubMed 5116171]

105. Crofts MAJ. Use of amphotericin B in mucocutaneous leishmaniasis. J Trop Med Hyg. 1976; 79:111-3. [PubMed 933229]

106. Singer C, Armstrong D, Jones TC et al. Imported mucocutaneous leishmaniasis in New York City: report of a patient treated with amphotericin B. Am J Med. 1975; 59:444-7. [PubMed 1163553]

107. Chulay JD. Cutaneous leishmaniasis of the new world. In: Strickland GT, ed. Hunter’s tropical medicine. 6th ed. Philadelphia: WB Saunders; 1984:589-93.

108. Report of a WHO Expert Committee. The Leishmaniases. Technical Report Series No. 701. Geneva: World Health Organization; 1984.

109. Kerdel-Vegas F. American leishmaniasis. Int J Dermatol. 1982; 21:291-303. [PubMed 6749711]

111. Berman JD. In vitro susceptibility of antimony-resistant Leishmania to alternative drugs. J Infect Dis. 1982; 145:279. [IDIS 146093] [PubMed 6274970]

112. McMillan B. The inhibition of leptomonads of the genus Leishmania in culture by antifungal agents. Ann Trop Med Parasitol. 1960; 54:293-300.

113. Ghosh BK, Ghosh A. The effects of antibiotics on Leishmania donovani. Dermatol Int. 1967; 6:154-60. [PubMed 5590117]

114. Berman JD, Wyler DJ. An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. J Infect Dis. 1980; 142:83-6. [PubMed 6249874]

115. Prata A. Treatment of kala-azar with amphotericin B. Trans R Soc Trop Med Hyg. 1963; 57:266-8. [PubMed 14047022]

116. Yesudian P, Thambiah AS. Amphotericin B therapy in dermal leishmanoid. Arch Dermatol. 1974; 109:720-2. [PubMed 4828540]

117. Chulay JD, Manson-Bahr PEC. Visceral leishmaniasis (kala-azar). In: Strickland GT, ed. Hunter’s tropical medicine. 6th ed. Philadelphia: WB Saunders Company; 1984:578-85.

118. Carter RF. Sensitivity to amphotericin B of a Naegleria sp. isolated from a case of primary amoebic meningoencephalitis. J Clin Pathol. 1969; 22:470-4. [PubMed 5798635]

119. Duma RJ, Rosenblum WI, McGehee RF et al. Primary amoebic meningoencephalitis caused by Naegleria: two new cases, response to amphotericin B, and a review. Ann Intern Med. 1971; 74:861-9. [PubMed 5580636]

120. Schuster FL, Rechthand E. In vitro effects of amphotericin B on growth and ultrastructure of the amoeboflagellates Naegleria gruberi and Naegleria fowleri. Antimicrob Agents Chemother. 1975; 8:591-605.

121. Duma RJ, Finley R. In vitro susceptibility of pathogenic Naegleria and Acanthamoeba species to a variety of therapeutic agents. Antimicrob Agents Chemother. 1976; 10:370-6. [IDIS 66432] [PubMed 984777]

122. Anderson K, Jamieson A. Primary amoebic meningoencephalitis. Lancet. 1972; 1:902-3. [PubMed 4111856]

123. Apley J, Clarke SKR, Roome APCH et al. Primary amoebic meningoencephalitis in Britain. Br Med J. 1970; 1:596-9. [PubMed 5440234]

124. Seidel JS, Harmatz P, Visvesvara GS et al. Successful treatment of primary amebic meningoencephalitis. N Engl J Med. 1982; 306:346-8. [IDIS 144049] [PubMed 7054710]

125. Nagington J, Richards JE. Chemotherapeutic compounds and Acanthamoebae from eye infections. J Clin Pathol. 1976; 29:648-51. [PubMed 185240]

126. Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone Inc; 1995:2300-9,2316-23,2336-8,2350-1,2371,2388-9,2413,2428-36,2714-9.

127. Ezdinli EZ, O’Sullivan DD, Wasser LP et al. Oral amphotericin for candidiasis in patients with hematologic neoplasms: an autopsy study. JAMA. 1979; 242:258-60. [PubMed 376883]

128. Dekker AW, Rozenberg-Arska M, Sixma JJ et al. Prevention of infection by trimethoprim-sulfamethoxazole plus amphotericin B in patients with acute nonlymphocytic leukaemia. Ann Intern Med. 1981; 95:555-9. [IDIS 139813] [PubMed 6794406]

129. Guiot HF, van der Meer JW, van Furth R. Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria. J Infect Dis. 1981; 143:644-54. [IDIS 134770] [PubMed 7017019]

130. Hann IM, Prentice HG, Corringham R et al. Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients. Lancet. 1982; 1:826-9. [IDIS 148623] [PubMed 6122057]

131. Kay HEM, Watson JG, Jameson B et al. Infection after bone marrow transplantation using cyclosporine. Transplantation. 1983; 36:491-5. [PubMed 6314614]

132. Wolff LJ. Supportive care for children with cancer. Guidelines of the Children’s Cancer Study Group. Use of prophylactic antibiotics. Am J Pediatr Hematol Oncol. 1984; 6:267-76. [PubMed 6393790]

133. Meunier-Carpentier F. Chemoprophylaxis of fungal infections. Am J Med. 1984; 76:652-6. [IDIS 183885] [PubMed 6324589]

134. Simor AE, Goswell G, Louis L et al. Antifungal susceptibility testing of yeast isolates from blood cultures by microbroth dilution and the E test. Eur J Clin Microb Infect Dis. 1997; 16:693-7.

135. Bristol-Myers Squibb. Fugizone (amphotericin B) injection, powder, lyophilized, for solution prescribing information. Princeton, NJ; 2009 Apr.

136. Gigliotti F, Shenep JL, Lott L et al. Induction of prostaglandin synthesis as the mechanism responsible for the chills and fever produced by infusing amphotericin B. J Infect Dis. 1987; 156:784-9. [IDIS 243048] [PubMed 3309074]

137. Scott EN, Kaufman L, Brown AC et al. Serologic studies in the diagnosis and management of meningitis due to Sporothrix schenckii. N Engl J Med. 1987; 317:935-40. [PubMed 3306388]

138. Gullberg RM, Quintanilla A, Levin ML et al. Sporotrichosis: recurrent cutaneous, articular, and central nervous system infection in a renal transplant recipient. Rev Infect Dis. 1987; 9:369-75. [IDIS 228172] [PubMed 3296101]

139. Freeman JW, Ziegler DK. Chronic meningitis caused by Sporotrichum schenckii. Neurology. 1977; 27:989-92. [IDIS 115612] [PubMed 561914]

140. Klein RC, Ivens MS, Seabury JH et al. Meningitis due to Sporotrichum schenckii. Arch Intern Med. 1966; 118:145-9. [PubMed 5329613]

141. Mozaffarian N, Berma JW, Casadevall A. Enhancement of nitric oxide synthesis by macrophages represens an additional mechanism of amphotericin B. Antimicrob Agents Chemother. 1997; 41:1825-9. [PubMed 9257771]

142. Holmes B, Brogden RN, Richards DM. Norfloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1985; 30:1-11.

143. Overbeek BP, Rozenberg-Arska M, Verhoef J. Do quinolones really augment the antifungal effect of amphotericin B in vitro? Drugs Exp Clin Res. 1985; 11:745-6.

144. Zuger A, Schuster M, Simberkoff MS et al. Maintenance amphotericin B for cryptococcal meningitis in acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988; 109:592-3. [IDIS 246239] [PubMed 3421567]

145. Zuger A, Louie E, Holzman RS et al. Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment. Ann Intern Med. 1986; 104:234-40. [IDIS 213659] [PubMed 3946951]

146. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

147. National Institutes of Health Office of Medical Applications of Research. Consensus development conference statement: Oral complications of cancer therapies: diagnosis, prevention, and treatment. 1989:7.

149. ASHP Commission on Therapeutics. ASHP therapeutic guidelines on nonsurgical antimicrobial prophylaxis. Clin Pharm. 1990; 9:423-45. [IDIS 267226] [PubMed 2194737]

150. Li PK, Lai KN. Amphotericin B induced ocular toxicity in cryptococcal meningitis. Br J Ophthalmol. 1989; 73:397-8. [PubMed 2730866]

151. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988; 32:1-8. [IDIS 243869] [PubMed 2831809]

152. Dismukes WE. Azole antifungal drugs: old and new. Ann Intern Med. 1988; 109:177-9. [IDIS 244739] [PubMed 2839058]

153. Foulds G, Brennan DR, Wajszczuk C et al. Fluconazole penetration into cerebrospinal fluid in humans. J Clin Pharmacol. 1988; 28:363-6. [IDIS 241029] [PubMed 2839557]

155. Sugar AM, Saunders C. Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988; 85:481-9. [IDIS 247330] [PubMed 2845779]

156. Dupont B, Drouhet E. Cryptococcal meningitis and fluconazole. Ann Intern Med. 1987; 106:778. [IDIS 229441] [PubMed 3032037]

157. Byrne WR, Wajszczuk CP. Cryptococcal meningitis in the acquired immunodeficiency syndrome (AIDS): successful treatment with fluconazole after failure of amphotericin B. Ann Intern Med. 1988; 108:384-5. [IDIS 239620] [PubMed 2829678]

158. Esposito R, Foppa CU, Antinori S. Fluconazole for cryptococcal meningitis. Ann Intern Med. 1989; 110:170. [IDIS 250518] [PubMed 2535777]

159. Stern JJ, Hartman BJ, Sharkey P et al. Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med. 1988; 85:477-80. [IDIS 247329] [PubMed 2845778]

160. Tozzi V, Bordi E, Galgani S et al. Fluconazole treatment of cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1989; 87:353. [IDIS 258429] [PubMed 2549790]

161. Larsen RA, Bozzette S, McCutchan A et al. Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. The California Collaborative Treatment Group. Ann Intern Med. 1989; 111:125-8. [IDIS 257101] [PubMed 2545124]

162. Glatt AE, Chirgwin K, Landesman SH. Treatment of infections associated with human immunodeficiency virus. N Engl J Med. 1988; 318:1439-48. [IDIS 241931] [PubMed 3285211]

163. De Wit S, Weerts D, Goossens H et al. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet. 1989; 1:746-8. [IDIS 253561] [PubMed 2564563]

164. Jacobson CE (Roerig, New York, NY): Personal communication; 1989 Feb 28.

165. Mau S, Salamone FR, Muller RJ et al. Trimetrexate, ganciclovir, foscarnet and fluconazole: investigational drugs used in the management of AIDS. Hosp Pharm. 1989; 24:209-15.

166. Jones PD, Marriott D, Speed BR. Efficacy of fluconazole in cryptococcal meningitis. Diagn Microbiol Infect Dis. 1989; 12:235S-8S. [PubMed 2556240]

167. Warnock DW. Itraconazole and fluconazole: new drugs for deep fungal infection. J Antimicrob Chemother. 1989; 24:275-80. [PubMed 2553654]

168. Washton H. Review of fluconazole: a new triazole antifungal agent. Diagn Microbiol Infect Dis. 1989; 12:229S-33S. [PubMed 2556239]

169. Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis. 1988; 157:624-8. [IDIS 239669] [PubMed 3279135]

170. Dismukes WE, Cloud G, Gallis HA et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987; 317:334-41. [IDIS 232272] [PubMed 3299095]

171. Panther LA, Sande MA. Cryptococcal meningitis in the acquired immunodeficiency syndrome. Semin Respir Infect. 1990; 5:138-45. [PubMed 2247708]

172. Eng RHK, Bishburg E, Smith SM et al. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986; 81:19-23. [PubMed 3524224]

173. Walsh TJ, Pizzo A. Treatment of systemic fungal infections: recent progress and current problems. Eur J Clin Microbiol Infect Dis. 1988; 7:460-75. [PubMed 2846299]

174. Sugar AM, Stern JJ, Dupont B. Overview: treatment of cryptococcal meningitis. Clin Infect Dis. 1990; 12(Suppl 3):S338-48.

175. National Institute of Allergy and Infectious Diseases, Division of AIDS. A note to physicians: important information on results of a control clinical trial of fluconazole vs. amphotericin B for suppression of cryptococcal meningitis. Bethesda, MD: 1990 April 30.

176. Roerig, New York, NY: Personal communication.

177. Anon. Fluconazole. Med Lett Drugs Ther. 1990; 32:50-2. [PubMed 2185400]

179. Grant SM, Clissold SP. Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs. 1990; 39:877-916. [PubMed 2196167]

180. Larsen RA, Leal MA, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med. 1990; 113:183-7. [IDIS 268747] [PubMed 2197908]

181. McKinsey DS, Gupta MR, Riddler SA et al. Long-term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS). Ann Int Med. 1989; 111:655-9. [IDIS 259881] [PubMed 2802421]

182. Larsen RA, Leal MAE, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS: a randomized trial. Ann Int Med. 1990; 113:183-7. [IDIS 268747] [PubMed 2197908]

183. Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med. 1989; 321:794-9. [IDIS 259126] [PubMed 2671735]

184. Wong RD, Goetz MB. Treatment of cryptococcal meningitis in AIDS. Ann Int Med. 1990; 113:992.

185. Bozzette SA, Larsen RA, Chiu J et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med. 1991; 324:580-4. [IDIS 278071] [PubMed 1992319]

186. Bozzette SA, Larsen RA, Chiu J et al. Fluconazole treatment of persistent Cryptococcus neoformans prostatic infection in AIDS. Ann Intern Med. 1991; 115:285-6. [IDIS 284358] [PubMed 1854112]

187. Davidson RN, Croft SL, Scott A et al. Liposomal amphotericin B in drug-resistant visceral leishmaniasis. Lancet. 1991; 337:1061-2. [IDIS 280509] [PubMed 1673494]

188. Schürman D, De Matos Marques B, Grünewald T et al. Safety and efficacy of liposomal amphotericin B in treating AIDS-associated disseminated cryptococcus. J Infect Dis. 1991; 1164:620-2.

189. Coker R, Horner J. Short-course treatment and response to liposomal amphotericin B in AIDS-associated cryptococcus. J Infect Dis. 1992; 11165:593.

190. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food Drug and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to November 30, 1991. Rockville, MD; 1992 Sep.

191. Bristol-Myers Squibb, Princeton, J: Personal communication.

192. Saag MS, Powderly WG, Cloud GA et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med. 1992; 326:83-9. [IDIS 289749] [PubMed 1727236]

193. Powderly WG, Saag M, Cloud GA et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 326:793-8. [IDIS 293046] [PubMed 1538722]

194. Coker R, Tomlinson D, Harris J. Successful treatment of cryptococcal meningitis with liposomal amphotericin B after failure of treatment with fluconazole and conventional amphotericin B AIDS. 1991; 5:231-2.

195. Fisher NC, Singhal S, Miller SJ et al. Fungal infection and liposomal amphotericin B (AmBisome) therapy in liver transplantation: a 2 year review. J Antimicrob Chemother. 1999; 43:597-600. [IDIS 427724] [PubMed 10350395]

196. de Lalla F, Pellizzer G, Vaglia A et al. Amphotericin B as primary therapy for cryptococcoses in patients with AIDS: reliability of relatively high doses administered over a relatively short period. Clin Infect Dis. 1995; 20:263-6. [IDIS 343229] [PubMed 7742427]

197. American Thoracic Society. Fungal infection in HIV-infected persons. Am J Respir Crit Care Med. 1995; 152:816-22. [IDIS 352046] [PubMed 7633749]

199. Wright DG, Robichaud KJ, Pizzo PA et al. Lethal pulmonary reactions associated with the combined use of amphotericin b and leukocyte transfusions. N Engl J Med. 1981; 304:1185-9. [IDIS 130639] [PubMed 7219459]

200. Bristol-Myers Squibb Oncology. Fungizone oral suspension (amphotericin B oral suspension) prescribing information (dated 1996 Jan). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:704-5.

201. Sigma-Tau Pharmaceuticals, Inc. ABELCET (amphotericin B lipid complex; amphotericin B, dimyristoylphosphatidylcholine, dl- and dimyristoylphosphatidylglycerol, dl- injection) prescribing information. Gaithersburg, MD; 2010 May.

202. Astellas Pharma US, Inc. AmBisome (amphotericin B liposome) powder for injection prescribing information. Northbrook, IL; 2012 May.

203. Kadmon Pharmaceuticals, Inc. Amphotec (amphotericin B cholesteryl sulfate complex; amphotericin B liquid complex) for injection prescribing information. Warrendale, PA; 2005 Jul.

204. Liposome Company, Inc. ABELCET (amphotericin B lipid complex injection) product monograph. Princeton, NJ; 1996 Apr.

205. Janknegt R, de Marie S, Bakker-Woudenberg IAJM et al. Liposomal and lipid formulations of amphotericin B: clinical pharmacokinetics. Clin Pharmacokinet. 1992; 23:279-91. [PubMed 1395361]

206. Heimez JW, Walsh TJ. Lipid formulations of amphotericin B: recent progress and future directions. Clin Infect Dis. 1996; 22(Suppl 2):S135-44. [IDIS 367019] [PubMed 8722841]

207. Rapp RP, Gubbins PO, Evans ME. Amphotericin B lipid complex. Ann Pharmacother. 1997; 31:1174-86. [IDIS 392971] [PubMed 9337444]

208. Stevens DA. Overview of amphotericin B colloidal dispersion (Amphocil). J Infect. 1994; 28(Suppl 1):45-9. [IDIS 329941] [PubMed 8077690]

209. Hay RJ. Liposomal amphotericin B, AmBisome. J Infect. 1994; 28(Suppl 1):35-43. [IDIS 329940] [PubMed 8077689]

210. Szoka FC, Tang. Amphotericin B formulated in liposomes and lipid based systems: a review. J Liposome Res. 1993; 3:363-75.

211. Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Clin Infect Dis. 1990; 12:308-29.

213. Powderly WG. Recent advances in the management of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996; 22(Suppl 2):S119-23.

214. Van der Horst CM, Saag MS, Cloud GA et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997; 337:15-21. [IDIS 387972] [PubMed 9203426]

215. Leenders ACAP, Reis P, Portegies P et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associate cryptococcal meningitis. AIDS. 1997; 11:1463-71. [PubMed 9342068]

216. Sharkey PK, Graybill JR, Johnson ES et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996; 22:315-21. [IDIS 363353] [PubMed 8838189]

217. Joly V, Aubry P, Ndayiragide A et al. Randomized comparison of amphotericin B deoxycholate dissolved in dextrose or intralipid for the treatment of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1996; 23:556-62. [IDIS 375080] [PubMed 8879780]

218. Kelly SL, Lamb DC, Kelly DE et al. Resistance to fluconazole and amphotericin in Candida albicans from AIDS patients. Lancet. 1996; 348:1523-4. [IDIS 377911] [PubMed 8942815]

219. Oppenheim BA, Herbrecht R, Kusne S. The safety and efficacy of amphotericin B colloidal dispersion in the treatment of invasive mycoses. Clin Infect Dis. 1995; 21:1145-53. [IDIS 356530] [PubMed 8589134]

220. Valero G, Graybill JR. Successful treatment of cryptococcal meningitis with amphotericin B colloidal dispersion: report of four cases. Antimicrob Agents and Chemother. 1995; 39:2588-90.

221. Goldani LZ, Sugar A. Paracoccidioidomycosis and AIDS: an overview. Clin Infect Dis. 1995; 21:1275-81. [IDIS 356544] [PubMed 8589154]

222. Barson WJ, Marcon MJ. Successful therapy of Candida albicans arthritis with a sequential intravenous amphotericin B and oral fluconazole regimen. Pediatr Infect Dis J. 1996; 15:1119-22. [IDIS 378161] [PubMed 8970223]

223. Rex JH, Bennett JE, Sugar AM et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med. 1994; 331:1325-30. [IDIS 338320] [PubMed 7935701]

224. Meunier F. Management of candidemia. N Engl J Med. 1994; 331:1371-2. [IDIS 338323] [PubMed 7935710]

225. Graybill JR. Editorial response: can we agree on the treatment of candidiasis? Clin Infect Dis. 1997; 25:60-2.

227. Kauffman CA. Role of azoles in antifungal therapy. Clin Infect Dis. 1996; 22(Suppl 2:S148-53. [IDIS 367021] [PubMed 8722843]

228. Dromer F, Mathoulin S, Dupont B et al. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. Clin Infect Dis. 1996; 22(Suppl 2:S154-60. [IDIS 367022] [PubMed 8722844]

229. Meunier F, Sculier JP, Coune A et al. Amphotericin B encapsulated in liposomes administered to cancer patients. Ann NY Acad Sci. 1988; 544:598-610. [PubMed 2850759]

230. Ringdén O, Meunier F, Tollemar J et al. Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients. J Antimicrob Chemother. 1991; 28(Suppl B):73-82. [PubMed 1778894]

231. Ng TTC, Dening DW. Liposomal amphotericin B (AmBisome) therapy of invasive fungal infections: evaluation of United Kingdom compassionate use data. Arch Intern Med. 1995; 155:1093-8. [IDIS 347712] [PubMed 7748054]

232. Lopez-Berestein G, Bodey GP, Fainstein V et al. Treatment of systemic fungal infections with liposomal amphotericin B. Arch Intern Med. 1989; 149:2533-6. [IDIS 260619] [PubMed 2818111]

233. de Marie S, Janknegt R, Bakker-Woudenberg IAJM. Clinical use of liposomal and lipid-complexed amphotericin B. J Antimicrob Chemother. 1993; 33:907-16.

234. Wieb VJ, DeGregorio W. Liposome-encapsulated amphotericin B: a promising new treatment for disseminated fungal infections. Rev Infect Dis. 1988; 10:1097-101. [IDIS 249719] [PubMed 3060940]

235. Oravcova E, Mistrik M, Sakalova A et al. Amphotericin B lipid complex to treat invasive fungal infections in cancer patients: report of efficacy and safety in 20 patients. Chemotherapy. 1995; 41:473-6. [IDIS 358134] [PubMed 8529439]

236. Denning DW. Treatment of invasive aspergillosis. J Infect. 1994; 28(Suppl 1):25-33. [IDIS 329939] [PubMed 8077688]

237. Kline MW, Bocobo FC, Paul ME et al. Successful medical therapy of Aspergillus. osteomyelitis of the spine in an 11-year-old boy with chronic granulomatous disease. Pediatrics. 1994; 93:830-5. [IDIS 329508] [PubMed 8165091]

238. Hospenthal DR, Byrd JC, Weiss RB. Successful treatment of invasive aspergillosis complicating prolonged treatment-related neutropenia in acute myelogenous leukemia with amphotericin B lipid complex. Med Pediatr Oncol. 1995; 25:119-22. [PubMed 7603397]

239. Jones RS, Barman A, Suh B et al. Successful treatment of Aspergillus vertebral osteomyelitis with amphotericin B lipid complex. Infect Dis Clin Pract. 1998; 237-9.

240. Richard EM, Apperley JF, Marchus RE. Successful use of liposome encapsulated amphotericin to treat invasive aspergillosis following failure of conventional amphotericin. Clin Lab Haematol. 1992; 14:127-30. [PubMed 1633682]

241. Khan AU, Gopalakrishnan G, Al-Awadi K et al. Renal aspergilloma due to Aspergillus flavus. Clin Infect Dis. 1995; 21:210-2. [IDIS 351444] [PubMed 7578735]

242. Polo JM, Fabrega E, Casafont F et al. Treatment of cerebral aspergillosis after liver transplantation. Neurology. 1992; 42:1817-9. [IDIS 301873] [PubMed 1513474]

243. Bodey GP, Vartivarian S. Aspergillosis. Eur J Clin Microbiol Infect Dis. 1989; 8:413-37. [PubMed 2502407]

244. White MH, Anaissie EJ, Kusne S et al. Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis. Clin Infect Dis. 1997; 24:635-42. [IDIS 384361] [PubMed 9145737]

245. Pappagianis D. Coccidioidomycosis. Semin Dermatol. 1993; 12:301-9. [PubMed 8312146]

246. Sundar S, Agrawal NK, Sinha PR et al. Short-course, low-dose amphotericin B lipid complex therapy for visceral leishmaniasis unresponsive to antimony. Ann Intern Med. 1997; 127:133-7. [IDIS 387930] [PubMed 9230003]

247. di Martino L, Davidson RN, Giacchinno R et al. Treatment of visceral leishmaniasis in children with liposomal amphotericin B. J Pediatr. 1997; 131:271-7. [IDIS 392296] [PubMed 9290615]

248. Hibberd PL, Rubin RH. Clinical aspects of fungal infection in organ transplant recipients. Clin Infect Dis. 1994; 19(Suppl 1):S33-40. [IDIS 335127] [PubMed 7948569]

249. Riley DK, Pavia AT, Beatty PG et al. The prophylactic use of low-dose amphotericin B in bone marrow transplant patients. Am J Med. 1994; 97:509-14. [IDIS 340188] [PubMed 7985709]

250. Bowden RA, Cays M, Gooley T et al. Phase I study of amphotericin B colloidal dispersion for the treatment of invasive fungal infections after marrow transplant. J Infect Dis. 1996; 173:1208-15. [IDIS 366951] [PubMed 8627074]

251. Leu HS, Huang CT. Clearance of funguria with short-course antifungal regimens: a prospective randomized, controlled study. Clin Infect Dis. 1995; 20:1152-7. [IDIS 347157] [PubMed 7619991]

252. Walsh TJ, Finberg RW, Arndt C et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999; 340:764-71. [IDIS 420561] [PubMed 10072411]

253. Davidson RN, di Martino L, Gradoni L et al. Short-course treatment of visceral leishmaniasis with liposomal amphotericin B (AmBisome). Clin Infect Dis. 1996; 22:938-43. [IDIS 368792] [PubMed 8783690]

254. Donowitz LG, Hendley JO. Short-course amphotericin B therapy for candidemia in pediatric patients. Pediatrics. 1995; 95:888-91. [IDIS 348549] [PubMed 7761216]

255. Driessen M, Ellis JB, Cooper PA et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996; 15:1107-12. [IDIS 378160] [PubMed 8970221]

256. Berman JD. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic development in the last 10 years. Clin Infect Dis. 1997; 24:684-703. [IDIS 384365] [PubMed 9145744]

257. Mishra M, Biswas UK, Jha AM et al. Amphotericin versus sodium stibogluconate in first-line treatment of Indian kala-azar. Lancet. 1994; 344:1599-600. [IDIS 339834] [PubMed 7983993]

258. Gold WL, Vellend H, Salit IE et al. Successful treatment of systemic and local infections due to Exophiala species. Clin Infect Dis. 1994; 19:339-41. [IDIS 334166] [PubMed 7986913]

259. Dietze R, Milan EP, Berman JD et al. Treatment of Brazilian Kala-Azar with a short course of Amphocil (amphotericin B cholesterol dispersion). Clin Infect Dis. 1993; 17:981-6. [IDIS 323153] [PubMed 8110956]

260. Fan-Havard P, O’Donovan C, Smith SM et al. Oral fluconazole versus amphotericin B bladder irrigation for treatment of candidal funguria. Clin Infect Dis. 1995; 21:960-5. [IDIS 355564] [PubMed 8645847]

261. Cross CE. Amphotericin B aerosol for transiently immunocompromised hosts: reasonably safe, but does it matter? Chest. 1995; 108:599-601. Editorial.

262. Hsu CCS, Chang RH. Two-day continuous bladder irrigation with amphotericin B. Clin Infect Dis. 1995; 20:1570-1. [IDIS 349030] [PubMed 7548519]

263. Arsura EL, Ismail Y, Freedman S et al. Amphotericin B-induced dilated cardiomyopathy. Am J Med. 1994; 97:560-2. [IDIS 340190] [PubMed 7985716]

264. Gales MA, Gales BJ. Rapid infusion of amphotericin B in dextrose. Ann Pharmacother. 1995; 29:523-9. [IDIS 348443] [PubMed 7655137]

265. Kline S, Larsen TA, Fieber L et al. Limited toxicity of prolonged therapy with high doses of amphotericin B lipid complex. Clin Infect Dis. 1995; 21:1154-8. [IDIS 356531] [PubMed 8589135]

266. Sanders SW, Buchi KN, Goddard MS et al. Single-dose pharmacokinetics and tolerance of a cholesteryl sulfate complex of amphotericin B administered to healthy volunteers. Antimicrob Agents Chemother. 1991; 35:1029-34. [IDIS 283437] [PubMed 1929241]

267. Pappas PG, Pottage JC, Powderly WG et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1992; 116:847-53. [IDIS 296295] [PubMed 1567099]

268. Denning DW, Stevens DA. Antifungal and surgical treatment of invasive aspergillosis: review or 2,121 published cases. Clin Infect Dis. 1990; 12:1147-201.

269. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 31st ed. London: The Pharmaceutical Press; 1996:383-402.

271. Despommier DD, Gwadz RW, Hotez PJ. Parasitic Diseases. 3rd ed. New York: Springer-Verlag; 1995:203-9.

273. Pizzo A. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993; 328:1323-32. [IDIS 313154] [PubMed 8469254]

274. Tollemar J, Hockerstedt K, Ericzon BG et al. Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study. Transplantation. 1995; 59:45-50. [IDIS 341433] [PubMed 7839427]

276. Schwartz S, Behre G, Heinemann V et al. Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood. 1999; 93:3654-61. [IDIS 427263] [PubMed 10339471]

277. Rowe JM, Ciobanu N, Ascensao J et al et al. Recommended guidelines for the management of autologous and allogeneic bone marrow transplantation: a report from the Eastern Cooperative Oncology Group (ECOG). Ann Intern Med. 1994; 120:143-58. [IDIS 323859] [PubMed 8256974]

278. Perfect JR. Antifungal prophylaxis: to prevent or not. Am J Med. 1993; 92:233-4.

279. Shelhamer JH, Toews GB, Masur H et al. Respiratory disease in the immunosuppressed patients. Ann Intern Med. 1992; 117:85-8. [IDIS 298558] [PubMed 1596052]

280. Yancey RW, Perlino CA, Kaufman L. Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases. J Infect Dis. 1991; 164:807-10. [IDIS 289561] [PubMed 1894941]

281. Pitrak DL, Anderson BR. Cerebral blastomycoma after ketoconazole therapy for respiratory tract blastomycosis. Am J Med. 1989; 86:713-4. [IDIS 255557] [PubMed 2729325]

282. Nishioka S. Paracoccidioidomycosis and AIDS. Clin Infect Dis. 1996; 22:1132. [IDIS 368827] [PubMed 8783743]

283. Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994; 220:263-72.

284. Paya CV. Fungal infections in solid-organ transplantation. Clin Infect Dis. 1993; 16:677-88. [IDIS 314580] [PubMed 8507760]

285. Galgiani JN, Ampel NM. Coccidioidomycosis in human immunodeficiency virus—infected patients. J Infect Dis. 1990; 162:1165-9. [IDIS 274447] [PubMed 2230241]

286. Rubin RH, Tolkoff-Rubin NE. Antimicrobial strategies in the care of organ transplant recipients. Antimicrob Agents Chemother. 1993; 37:619-24. [IDIS 312544] [PubMed 8494357]

287. Walsh TJ, Lee JW. Prevention of invasive fungal infections in patients with neoplastic diseases. Clin Infect Dis. 1993; 17(Suppl 2):S468-80. [IDIS 323669] [PubMed 8274613]

288. Klein NC, Cunha BA. New antifungal drugs for pulmonary mycoses. Chest. 1996; 110:525-32. [IDIS 371846] [PubMed 8697859]

289. Kauffman CA. Old and new therapies for sporotrichosis. Clin Infect Dis. 1995; 21:981-5. [IDIS 355567] [PubMed 8645851]

290. McWhinney PH, Kibbler CC, Hamonn MD et al. Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years’ experience. Clin Infect Dis. 1993; 17:397-404. [IDIS 319853] [PubMed 8218680]

291. Mangino JE, Pappas PG. Itraconazole for the treatment of histoplasmosis and blastomycosis. Int J Antimicrob Agents. 1995; 5:219-25. [PubMed 18611672]

292. Jacobs LG, Skidmore EA, Freeman K et al. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis. 1996; 22:30-5. [IDIS 360681] [PubMed 8824962]

294. Nguyen MH, Peacock JE, Morris AJ et al. The changing face of candidemia: emergence of non-C. albicans species and antifungal resistance. Am J Med. 1996; 100:617-23. [IDIS 370428] [PubMed 8678081]

295. Anaissie E, Bodey GP, Kantarjiann H et al. Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med. 1991; 91:142-50. [IDIS 286567] [PubMed 1867240]

296. Colville A, Wale MCJ. Fluconazole or amphotericin for candidaemia in non-neutropenic patients. Lancet. 1991; 337:1605-6. [IDIS 282588] [PubMed 1675729]

297. Soutar RL. Fluconazole or amphotericin for candidosis in neutropenic patients. Lancet. 1991; 337:181. [IDIS 276939] [PubMed 1670824]

298. Winston DJ, Chanrasekar PH, Lazarus HM et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia: results of a randomized placebo-controlled, double-blind multicenter trial. Ann Intern Med. 1993; 118:495-503. [IDIS 311491] [PubMed 8442620]

299. Powderly WG, Kobayashi GS, Herzig GP et al. Amphotericin B-resistant yeast infection in severely immunocompromised patients. Am J Med. 1988; 84:826-32. [IDIS 241199] [PubMed 3284339]

300. Menichetti F, Del Favero A, Martino P et al. Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Ann Intern Med. 1994; 120:913-8. [IDIS 330615] [PubMed 8172437]

301. Sanguineti A, Carmichael K, Campbell K. Fluconazole-resistant Candida albicans after long-term suppressive therapy. Arch Intern Med. 1993; 153:1122-4. [PubMed 8481078]

302. Pavia AT, Riley DK. Fluconazole prophylaxis in patients with leukemia. Ann Intern Med. 1993; 119:951. [IDIS 321009] [PubMed 8215009]

303. Akiyama H, Sakamaki H, Onozawa Y. Fluconazole prophylaxis in patients with leukemia. Ann Intern Med. 1993; 119:951. [IDIS 321008] [PubMed 8215008]

304. Galgiani JN, Catanzaro A, Cloud GA et al. Fluconazole therapy for coccidioidal meningitis. Ann Intern Med. 1993; 119:28-35. [IDIS 315934] [PubMed 8498760]

305. Martin E, Maier F, Bhakdi S. Antagonistic effects of fluconazole and 5-fluorocytosine on candidacidal action of amphotericin B in human serum. Antimicrob Agents Chemother. 1994; 28:1331-8.

306. Berry AJ, Rinaldi G, Graybill JR. Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS. Antimicrob Agents Chemother. 1992; 36:690-2. [IDIS 292623] [PubMed 1622188]

307. Anaissie EJ, Darouiche RO, Abi-Said D et al. Management of invasive candidal infections: results of a prospective, randomized multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis. 1996; 23:964-72. [IDIS 377538] [PubMed 8922787]

308. Klepser ME, Wolfe EJ, Jones RN et al. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997; 41:1392-5. [IDIS 394224] [PubMed 9174207]

309. Sanati H, Ramos CF, Bayer AS et al. Combination therapy with amphotericin B and fluconazole against invasive candidiasis in neutropenic-mouse and infective-endocarditis rabbit models. Antimicrob Agents Chemother. 1997; 41:1345-8. [PubMed 9174196]

310. Maenza JR, Merz WG, Romagnoli MJ et al. Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology. Clin Infect Dis. 1997; 24:28-34. [IDIS 378941] [PubMed 8994752]

311. Marins MD, Lozano-Chiu M, Rex JH. Point prevalence of oropharyngeal carriage of fluconazole-resistant Candida in human immunodeficiency virus-infected patients. Clin Infect Dis. 1997; 25:843-6. [IDIS 395790] [PubMed 9356799]

312. van Ettenn EWM, van de Rhee NE, van Kampen KM et al. Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans. Antimicrob Agents Chemother. 1991; 35:2275-81. [PubMed 1804000]

313. Witt MD, Imhoff T, Li C et al. Comparison of fluconazole and amphotericin B for treatment of experimental Candida endocarditis caused by non-C. albicans strains. Antimicrob Agents Chemother. 1993; 37:2030-2. [PubMed 8239628]

314. Sugar A, Hitchcock CA, Troke PF et al. Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. Antimicrob Agents Chemother. 1995; 39:598-601. [PubMed 7793858]

315. Walsh TJ, Peter J, McGough DA et al. Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii. Antimicrob Agents Chemother. 1995; 39:1361-4. [IDIS 348687] [PubMed 7574531]

316. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard. NCCLS document M27-A. Wayne, PA; NCCLS:1997 Jun.

317. Pfaller A, Rex JH, Rinaldi MG. Antifungal susceptibility testing: technical advances and potential clinical applications. Clin Infect Dis. 1997; 24:776-84. [IDIS 386039] [PubMed 9142769]

318. Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore). 1997; 76:339-54. [IDIS 395532] [PubMed 9352737]

319. Chao D, Steier KJ, Gomila R. Update and review of blastomycosis. J Am Osteopath Assoc. 1997; 97:525-32. [PubMed 9313349]

320. Bradsher RW. Therapy of blastomycosis. Semin Respir Infect. 1997; 12:263-7. [PubMed 9313298]

321. Varkey B. Blastomycosis in children. Semin Respir Infect. 1997; 12:235-42. [PubMed 9313295]

322. Chapman SW, Lin AC, Hendricks KA et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. 1997; 12:219-28. [PubMed 9313293]

323. Henequin C, Benailly N, Silly C et al. In vitro susceptibilities to amphotericin B, itraconazole, and miconazole of filamentous fungi isolated from patients with cystic fibrosis. Antimicrob Agents Chemother. 1997; 41:2064-6. [IDIS 393402] [PubMed 9303420]

324. Hopkins MA, Treloar DM. Mucormycosis in diabetes. Am J Crit Care. 1997; 6:363-7. [PubMed 9283673]

325. Law D, Moore CB, Denning DW. Amphotericin B resistance testing of Candida spp.: a comparison of methods. J Antimicrob Chemother. 1997; 40:109-12. [PubMed 9249212]

326. Osaka K, Ritov VB, Bernardo JF et al. Amphotericin B protects cis-parinaric acid against peroxyl radical-induced oxidation: amphotericin B as an antioxidant. Antimicrob Agents Chemother. 1997; 41:743-7. [PubMed 9087481]

327. Tohyama M, Kawakami K, Saito A. Anticryptococcal effect of amphotericin B is mediated through macrophage production of nitric oxide. Antimicrob Agents Chemother. 1996; 40:1919-23. [PubMed 8843304]

328. Kintzel PE. Amphotericin B in fat emulsion. Am J Health-Syst Pharm. 1996; 53:2701. [IDIS 375370] [PubMed 8931810]

329. Lopez RM, Ayestara A, Pou L et al. Stability of amphotericin B in a extemporaneously prepared i.v. fat emulsion. Am J Health-Syst Pharm. 1996; 53:2724-7. [IDIS 375374] [PubMed 8931814]

330. Heide PE. Precipitation of amphotericin B from i.v. fat emulsion. Am J Health-Syst Pharm. 1997; 54:1449. [IDIS 386400] [PubMed 9194992]

331. Owes D, Fleming RA, Restino MS et al. Stability of amphotericin B 0.05 and 0.5 mg/mL in 20% fat emulsion. Am J Health-Syst Pharm. 1997; 54:683-6. [IDIS 381388] [PubMed 9075499]

332. Heinemann V, Bosse D, Jehn U et al. Pharmacokinetics of liposomal amphotericin B (AmBisome) in critically ill patients. Antimicrob Agents Chemother. 1997; 41:1275-80. [IDIS 394210] [PubMed 9174183]

333. Kan VL, Bennett JE, Amantea MA et al. Comparison of safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. J Infect Dis. 1991; 164:418-21. [IDIS 286644] [PubMed 1856491]

334. Ayestaran A, Lopez R, Montoro JB et al. Pharmacokinetics of conventional formulation versus fat emulsion formulation of amphotericin B in a group of patients with neutropenia. Antimicrob Agents Chemother. 1996; 40:609-12. [IDIS 364372] [PubMed 8851579]

335. Heinemann V, Kahny B, Jehn U et al. Serum pharmacology of amphotericin B applied in lipid emulsions. Antimicrob Agents Chemother. 1997; 41:728-32. [IDIS 384383] [PubMed 9087478]

336. Sugar AM. Use of amphotericin B with azole antifungal drugs: what are we doing? Antimicrob Agents Chemother. 1995; 39:1907-12.

337. Walsh TJ, Whitcomb P, Piscitelli S et al. Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis. Antimicrob Agents Chemother. 1997; 41:1944-8. [IDIS 393392] [PubMed 9303390]

338. Amantea A, Bowden RA, Forrest A et al. Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants. Antimicrob Agents Chemother. 1995; 39:2042-7. [IDIS 353839] [PubMed 8540713]

339. Mitsutake K, Kohno S, Miyazaki Y et al. In vitro and in vivo antifungal activities of liposomal amphotericin B, and amphotericin B lipid complex. Mycopathologia. 1994; 128:13-7. [PubMed 7708087]

340. Wasan KM, Conklin JS. Enhanced amphotericin B nephrotoxicity in intensive care patients with elevated levels of low-density lipoprotein cholesterol. Clin Infect Dis. 1997; 24:78-80. [IDIS 378948] [PubMed 8994768]

341. Goodwin SD, Cleary JD, Walawander CA et al. Pretreatment regimens for adverse events related to infusion of amphotericin B. Clin Infect Dis. 1995; 20:755-61. [IDIS 346161] [PubMed 7795069]

342. Kingo ARM, Smyth JA, Waisman D. Lack of evidence of amphothericin B toxicity in very low birth weight infants treated for systemic candidiasis. Pediatr Infect Dis J. 1997; 16:1002-3. [IDIS 394574] [PubMed 9380454]

343. Alexander BD, Perfect JR. Antifungal resistance trends towards the year 2000. Implications for therapy and new approaches. Drugs. 1997; 54:657-78. [PubMed 9360056]

344. White MH, Bowden RA, Sandler E et al. Amphotericin colloidal dispersion (ABCD) vs. amphotericin B (AmB) in the empiric treatment of febrile neutropenic patients. Blood. 1996; 88(Suppl 1):302a.

345. Nicholl TA, Nimmo CR, Shepherd JD et al. Amphotericin B infusion-related toxicity: comparison of two- and four-hour infusions. Ann Pharmacother. 1995; 29:1081-7. [IDIS 357218] [PubMed 8573948]

346. Reviewers’ comments (personal observations).

347. Sequus Pharmaceuticals, Menlo Park, CA: Personal communication.

348. Noskin GA, Pietrelli L, Coffey G et al. Amphotericin B colloidal dispersion for treatment of candidemia in immunocompromised patients. Clin Infect Dis. 1998; 26:461-7. [PubMed 9502471]

349. Venkateswarlu K, Taylor M, Manning NJ et al. Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother. 1997; 41:748-51. [IDIS 384385] [PubMed 9087482]

350. Wingard JR. Infections due to resistant Candida species in patients with cancer who are receiving chemotherapy. Clin Infect Dis. 1994; 19(Suppl 1):S49-53. [IDIS 335129] [PubMed 7948571]

351. Walker S, Tailor SA, Lee M et al. Amphotericin B in lipid emulsion: stability, compatibility, and in vitro antifungal activity. Antimicrob Agents Chemother. 1998; 42:762-6. [PubMed 9559779]

352. Schoffski P, Freund M, Wunder R et al. Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study. BMJ. 1998; 317:379-84. [IDIS 411671] [PubMed 9694753]

353. Nath CE, Shaw PJ, Gunning R et al. Amphotericin B in children with malignant disease: a comparison of the toxicities and pharmacokinetics of amphotericin B administered in dextrose versus lipid emulsion. Antimicrob Agents Chemother. 1999; 43:1417-23. [IDIS 426253] [PubMed 10348763]

354. Nucci M, Loureiro M, Silveira F et al. Comparison of the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in fat emulsion in a randomized trial with cancer patients. Antimicrob Agents Chemother. 1999; 43:1445-8. [IDIS 426255] [PubMed 10348768]

355. Kauffman CA, Wiseman SW. Anaphylaxis upon switching lipid-containing amphotericin B formulations. Clin Infect Dis. 1998; 26:1237-8. [IDIS 407761] [PubMed 9597266]

356. Cronin JE, Barron RL. Anaphylaxis upon switching lipid-containing amphotericin B formulations. Clin Infect Dis. 1999; 28:1342. [IDIS 430888] [PubMed 10451192]

357. Gill J, Sprenger HR, Ralph ED et al. Hepatotoxicity possibly caused by amphotericin B. Ann Pharmacother. 1999; 33:683-5. [IDIS 428245] [PubMed 10410179]

358. Kelsey SM, Goldman JM, McCann S et al. Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study. Bone Marrow Transplantation. 1999; 23:163-8. [IDIS 423089] [PubMed 10197802]

359. Ellis ME, Al-Hokail AA, Clink HM et al. Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B. Antimicrob Agents Chemother. 1992; 36:172-9. [IDIS 289794] [PubMed 1590686]

360. Drutz DJ. Rapid infusion of amphotericin B: is it safe, effective, and wise? Am J Med. 1992; 93:119-21.

361. Bowler WA, Weiss PJ, Hill HE et al. Risk of ventricular dysrhythmias during 1-hour infusions of amphotericin B in patients with preserved renal function. Antimicrob Agents Chemother. 1992; 36:2542-3. [IDIS 304990] [PubMed 1489202]

362. Cruz JM, Peacock JE, Loomer L et al. Rapid intravenous infusion of amphotericin B: a pilot study. Am J Med. 1992; 93:123-30. [IDIS 300585] [PubMed 1497007]

363. Cleary JD, Hayman J, Sherwood J et al. Amphotericin B overdose in pediatric patients with associated cardiac arrest. Ann Pharmacother. 1993; 27:715-9. [IDIS 316094] [PubMed 8329789]

364. Clancy CJ, Yu YC, Lewin A et al. Inhibition of RNA synthesis as a therapeutic strategy against Aspergillus and Fusarium: demonstration of in vitro synergy between rifabutin and amphotericin B. Antimicrob Agents Chemother. 1998; 42:509-13. [IDIS 401364] [PubMed 9517924]

365. Antoniskis D, Larsen RA. Acute, rapidly progressive renal failure with simultaneous use of amphotericin B and pentamidine. Antimicrob Agents Chemother. 1990; 34:470-2. [IDIS 263860] [PubMed 2334159]

366. Strasser MD, Kennedy RJ, Adam RD. Rhinocerebral mucormycosis: therapy with amphotericin B lipid complex. Arch Intern Med. 1996; 156:337-9. [IDIS 363134] [PubMed 8572846]

367. Moses AE, Rahav G, Barenholz Y et al. Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patients. Clin Infect Dis. 1998; 26:1430-3. [IDIS 409166] [PubMed 9636875]

368. Naguib MT, Huycke MM, Pederson JA et al. Apophysomyces elegans infection in a renal transplant recipient. Am J Kidney Dis. 1995; 26:381-4. [PubMed 7645546]

369. Maury S, Leblanc T, Feuilhade M et al. Successful treatment of disseminated mucormycosis with liposomal amphotericin B and surgery in a child with leukemia. Clin Infect Dis. 1998; 26:200-2. [IDIS 419238] [PubMed 9455544]

370. Singh N, Mieles L, Yu VL et al. Invasive aspergillosis in liver transplant recipients: association with candidemia and consumption coagulopathy and failure of prophylaxis with low-dose amphotericin B. Clin Infect Dis. 1993; 17:906-8. [IDIS 321800] [PubMed 8286639]

371. Lorf T, Braun F, Ruchel R et al. Systemic mycoses during prophylactical use of liposomal amphotericin B (Ambisome) after liver transplantation. Mycoses. 1999; 42:47-53. [PubMed 10394848]

372. Ringden O, Andstrom EE, Remberger M et al. Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive fungal infections in children undergoing organ or allogeneic bone-marrow transplantation. Pediatr Transplantation. 1997; 1:124-9.

373. Noskin G, Pietrelli L, Gurwith M et al. Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients. Bone Marrow Transplantation. 1999; 23:697-703. [IDIS 426501] [PubMed 10218847]

374. Gotzsche PC, Johansen HK. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia. BMJ. 1997; 314:1238-44. [IDIS 384197] [PubMed 9154027]

375. Perfect JR, Klotman ME, Gilbert CC et al. Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients. J Infect Dis. 1992; 165:891-7. [IDIS 295414] [PubMed 1569339]

376. Malik IA, Moid I, Aziz Z et al. A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med. 1998; 105:478-83. [IDIS 420788] [PubMed 9870832]

377. Karp JE, Merz WG. Editorial response: randomized trial of lipid-based amphotericin B for invasive aspergillosis in neutropenic hosts is an important step forward. Clin Infect Dis. 1998; 27:1413-4. [IDIS 418648] [PubMed 9868652]

378. Severens JL, Donnelly JP, Meis JF et al. Two strategies for managing invasive aspergillosis: a decision analysis. Clin Infect Dis. 1997; 25:1148-54. [PubMed 9402374]

379. Ellis M, Spence D, de Pauw B et al. An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis. Clin Infect Dis. 1998; 27:1406-12. [IDIS 418647] [PubMed 9868651]

380. Torre-Cisneros J, Prada JL, Vilanueva JL et al. Successful treatment of antimony-resistant cutaneous leishmaniasis with liposomal amphotericin B. Clin Infect Dis. 1994; 18:1024-5. [IDIS 331764] [PubMed 8086540]

381. Davidson RN. Practical guide for the treatment of leishmaniasis. Drugs. 1998; 56:1009-18. [PubMed 9878989]

382. Laguna F, Lopez-Velez R, Pulido F et al. Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing meglumine antimoniate with amphotericin B. AIDS. 1999; 19:1063-9.

383. Boletis JN, Pefanis A, Stathakis C et al. Visceral leishmaniasis in renal transplant recipients: successful treatment with liposomal amphotericin B (AmBisome). Clin Infect Dis. 1999; 28:1308-9. [IDIS 430874] [PubMed 10451172]

384. Coukell AJ, Brogden RN. Liposomal amphotericin B: therapeutic use in the management of fungal infections and visceral leishmaniasis. Drugs. 1998; 55:585-612. [PubMed 9561346]

385. Brogden RN, Goa KL, Coukell AJ. Amphotericin-B colloidal dispersion: a review of its use against systemic fungal infections and visceral leishmaniasis. Drugs. 1998; 56:365-83. [PubMed 9777313]

386. Favel A, Michel-Nguyen A, Chastin C et al. In-vitro susceptibility pattern of Candida lusitaniae and evaluation of the Etest method. J Antimicrob Chemother. 1997; 39:591-6. [IDIS 387158] [PubMed 9184357]

387. Nolte FS, Parkinson T, Falconer DJ et al. Isolation and characterization of fluconazole- and amphotericin b-resistant Candida albicans from blood of two patients with leukemia. Antimicrob Agents Chemother. 1997; 44:196-9.

388. Lopez-Ribot JL, McAtee RK, Perea S et al. Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1999; 43:1621-30. [PubMed 10390213]

389. Moran GP, Sullivan DJ, Henman MC et al. Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro. Antimicrob Agents Chemother. 1997; 41:617-23. [IDIS 383166] [PubMed 9056003]

390. Sullivan D, Coleman D. Candida dubliniensis: characteristics and identification. J Clin Microbiol. 1998; 36:329-34. [PubMed 9466736]

391. Hoban DJ, Zhanel GG, Karlowsky JA. In vitro susceptibilities of Candida and Cryptococcus neoformans isolates from blood cultures of neutropenic patients. Antimicrob Agents Chemother. 1999; 43:1463-4. [PubMed 10348771]

392. Hennequin C, Benailly N, Silly C et al. In vitro susceptibilities to amphotericin B, itraconazole, and miconazole of filamentous fungi isolated from patients with cystic fibrosis. Antimicrob Agents Chemother. 1997; 41:2064-6. [IDIS 393402] [PubMed 9303420]

393. Robinson PA, Bauer M, Leal MAE et al. Early mycological treatment failure in AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999; 28:82-92. [IDIS 422107] [PubMed 10028076]

394. Koehler AP, Cheng AFB, Chu KC et al. Successful treatment of disseminated coccidioidomycosis with amphotericin B lipid complex. J Infect. 1998; 36:113-5. [IDIS 405116] [PubMed 9515680]

395. Walsh TJ, Yeldandi V, McEvoy M et al. Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients. Antimicrob Agents Chemother. 1998; 42:2391-8. [IDIS 412434] [PubMed 9736569]

396. Walsh TJ, Hiemenz JW, Seibel NL et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis. 1998; 26:1383-96. [IDIS 409162] [PubMed 9636868]

397. Denning DW, Marinus A, Cohen J et al. An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diagnosis and therapeutic outcome. J Infect. 1998; 37:173-80. [PubMed 9821093]

398. Walsh TJ, Seibel JL, Arndt C et al. Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J. 1999; 18:702-8. [IDIS 432094] [PubMed 10462340]

399. Yoon SA, Vazquez JA, Steffan PE et al. High-frequency, in vitro reversible switching of Candida lusitaniae clinical isolates from amphotericin B susceptibility to resistance. Antimicrob Agents Chemother. 1999; 43:836-45. [PubMed 10103188]

400. Gumbo T, Isada CM, Hall G et al. Candida glabrata fungemia: clinical features of 139 patients. Medicine (Baltimore). 1999; 78:220-7. [IDIS 434422] [PubMed 10424204]

401. Scarcella A, Pasquariello MB, Giugliano B et al. Liposomal amphotericin B treatment for neonatal fungal infections. Pediatr Infect Dis J. 1998; 17:146-8. [IDIS 401106] [PubMed 9493812]

402. Pfaller MA, Messer SA, Hollis RJ. Strain delineation and antifungal susceptibilities of epidemiologically related and unrelated isolates of Candida lusitaniae. Diagn Microbiol Infect Dis. 1994; 20:127-33. [PubMed 7874879]

403. Arishi HA, Frayha HH, Kalloghlian A et al. Liposomal amphotericin B in neonates with invasive candidiasis. Am J Perinatol. 1997; 14:573-6. [PubMed 9394170]

404. Catania S, Aiassa C, Tzahtzoglou S et al. Visceral leishmaniasis treated with liposomal amphotericin B. Pediatr Infect Dis J. 1999; 18:73-4. [IDIS 421876] [PubMed 9951989]

405. Aguilar C, Pujol I, Guarro J. In vitro antifungal susceptibilities of Scopulariopsis isolates. Antimicrob Agents Chemother. 1999; 43:1520-2. [IDIS 426263] [PubMed 10348787]

406. Sirisanthana T, Supparatpinyo K, Perriens J et al. Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients. Clin Infect Dis. 1998; 26:1107-10. [PubMed 9597237]

407. Supparatpinyo K, Perriens J, Nelson KE et al. A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus. N Engl J Med. 1998; 339:1739-43. [PubMed 9845708]

408. Wu TC, Chan JW, Ng CK et al. Clinical presentations and outcomes of Penicillium marneffei infections: a series from 1994 to 2004. Hong Kong Med J. 2008; 14:103-9. [PubMed 18382016]

409. Sar B, Boy S, Keo C et al. In vitro antifungal-drug susceptibilities of mycelial and yeast forms of Penicillium marneffei isolates in Cambodia. J Clin Microbiol. 2006; 44:4208-10. [PubMed 16971649]

410. Lin JN, Lin HH, Lai CH et al. Renal transplant recipient infected with Penicillium marneffei. Lancet Infect Dis. 2010; 10:138. [PubMed 20113983]

411. Aberg JA, Price RW, Heeren DM et al. A pilot study of the discontinuation of antifungal therapy for disseminated cryptococcal disease in patients with acquired immunodeficiency syndrome, following immunologic response to antiretroviral therapy. J Infect Dis. 2002; 185:1179-82. [IDIS 479822] [PubMed 11930330]

412. Mussini C, Pezzotti P, Miró JM et al. Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy: an international observational study. Clin Infect Dis. 2004; 38:565-71. [PubMed 14765351]

413. Centers for Disease Control and Prevention. Gastrointestinal basidiobolomycosis—Arizona. MMWR Morb Mortal Wkly Rep. 1999; 48:710-3. [PubMed 21033182]

414. Basidiobolus ranarum as an etiologic agent of gastrointestinal zygomycosis. J Clin Microgiol. 2001; 39:2360-3.

415. Lyon GM, Smilack JD, Komatsu KK et al. Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological characteristics and review of the literature. Clin Infect Dis. 2001; 32:1448-55. [PubMed 11317246]

416. Zavasky DM, Samowitz W, Loftus T et al. Gastrointestinal zygomycotic infection caused by Basidiobolus ranarum: case report and review. Clin Infect Dis. 1999; 28:1244-8. [IDIS 430866] [PubMed 10451160]

417. X-Gen Pharmaceuticals, Inc. Amphotericin B for injection prescribing information. Big Flats, NY; 2009 Dec.

418. Almyroudis NG, Sutton DA, Fothergill AW et al. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother. 2007; 51:2587-90. [PubMed 17452481]

419. Dannaoui E, Meletiadis J, Mouton JW et al. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother. 2003; 51:45-52. [PubMed 12493786]

420. Bowden R, Chandrasekar P, White MH et al. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2002; 35:359-66. [PubMed 12145716]

421. Guarro J, Aguilar C, Pujol I. In-vitro antifungal susceptibilities of Basidiobolus and Conidiobolus spp. strains. J Antimicrob Chemother. 1999; 44:557-60. [PubMed 10588321]

422. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Disease Society of America. Clin Infect Dis. 2011; 52:e56-93.

423. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46:327-60. [PubMed 18177225]

424. Chapman SW, Dismukes WE, Proia LA et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46:1801-12. [PubMed 18462107]

425. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:503-35. [PubMed 19191635]

426. Galgiani JN, Ampel NM, Blair JE et al. Coccidioidomycosis. Clin Infect Dis. 2005; 41:1217-23. [PubMed 16206093]

427. Perfect JR, Dismukes WE, Dromer F et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50:291-322. [PubMed 20047480]

428. Wheat LJ, Freifeld AG, Kleiman MB et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007; 45:807-25. [PubMed 17806045]

429. Kauffman CA, Bustamante B, Chapman SW et al. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007; 45:1255-65. [PubMed 17968818]

432. Wise GJ, Kozinn PJ, Goldberg P. Amphotericin B as a urologic irrigant in the management of noninvasive candiduria. J Urol. 1982; 128:82-4. [PubMed 7109077]

433. Paladino JA, Crass RE. Amphotericin B and flucytosine in the treatment of candidal cystitis. Clin Pharm. 1982 Jul-Aug; 1:349-52.

434. Fisher JF, Chew WH, Shadomy S et al. Urinary tract infections due to Candida albicans. Rev Infect Dis. 1982 Nov-Dec; 4:1107-18.

435. Gross MH, Pickard WW, Perfect JR. Retrospective review of amphotericin B use in a tertiary-care medical center. Am J Hosp Pharm. 1987; 44:1353-7. [PubMed 3618612]

436. . Antifungal drugs. Treat Guidel Med Lett. 2012; 10:61-8; quiz 69-70. [PubMed 22825657]

440. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (May 7, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

441. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58(RR-11):1-166. [PubMed 19730409]

442. Anon. Drugs for parasitic infections. Treat Guidel Med Lett. 2010; 8 (suppl). From the Medical Letter website.

443. Murray HW, Berman JD, Davies CR et al. Advances in leishmaniasis. Lancet. 2005 Oct 29-Nov 4; 366:1561-77.

444. Bern C, Adler-Moore J, Berenguer J et al. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis. 2006; 43:917-24. [PubMed 16941377]

445. Imwidthaya P, Thipsuvan K, Chaiprasert A et al. Penicillium marneffei: types and drug susceptibility. Mycopathologia. 2001; 149:109-15. [PubMed 11307592]

446. Ramani R, Chaturvedi V. Antifungal susceptibility profiles of Coccidioides immitis and Coccidioides posadasii from endemic and non-endemic areas. Mycopathologia. 2007; 163:315-9. [PubMed 17484074]

447. Cordeiro RA, Brilhante RS, Rocha MF et al. In vitro activities of caspofungin, amphotericin B and azoles against Coccidioides posadasii strains from Northeast, Brazil. Mycopathologia. 2006; 161:21-6. [PubMed 16389480]

448. Bariola JR, Perry P, Pappas PG et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010; 50:797-804. [PubMed 20166817]

449. Hamill RJ, Sobel JD, El-Sadr W et al. Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety. Clin Infect Dis. 2010; 51:225-32. [PubMed 20536366]

450. Okamoto K, Hatakeyama S, Itoyama S et al. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis. 2010; 16:1155-7. [PubMed 20587194]

451. Grosse P, Tintelnot K, Söllner O et al. Encephalomyelitis due to Cryptococcus neoformans var gattii presenting as spinal tumour: case report and review of the literature. J Neurol Neurosurg Psychiatry. 2001; 70:113-6. [PubMed 11118259]

452. Goldberg E, Gafter-Gvili A, Robenshtok E et al. Empirical antifungal therapy for patients with neutropenia and persistent fever: Systematic review and meta-analysis. Eur J Cancer. 2008; 44:2192-203. [PubMed 18706808]

453. Gomez-Lopez A, Zaragoza O, Dos Anjos Martins M et al. In vitro susceptibility of Cryptococcus gattii clinical isolates. Clin Microbiol Infect. 2008; 14:727-30. [PubMed 18558948]

454. Galanis E, Hoang L, Kibsey P et al. Clinical presentation, diagnosis and management of Cryptococcus gattii cases: Lessons learned from British Columbia. Can J Infect Dis Med Microbiol. 2009; 20:23-8. [PubMed 20190892]

455. Glick JA, Graham RS, Voils SA. Candida meningitis post Gliadel wafer placement successfully treated with intrathecal and intravenous amphotericin B. Ann Pharmacother. 2010; 44:215-8. [PubMed 20028954]

456. Zmierczak H, Goemaere S, Mielants H et al. Candida glabrata arthritis: case report and review of the literature of Candida arthritis. Clin Rheumatol. 1999; 18:406-9. [PubMed 10524556]

457. Stevens DA, Shatsky SA. Intrathecal amphotericin in the management of coccidioidal meningitis. Semin Respir Infect. 2001; 16:263-9. [PubMed 11740828]

458. Herbrecht R, Denning DW, Patterson TF et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002; 347:408-15. [IDIS 484720] [PubMed 12167683]

459. Cornely OA, Maertens J, Bresnik M et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007; 44:1289-97. [PubMed 17443465]

460. Marino E, Gallagher JC. Prophylactic antifungal agents used after lung transplantation. Ann Pharmacother. 2010; 44:546-56. [PubMed 20179260]

461. Borro JM, Solé A, de la Torre M et al. Efficiency and safety of inhaled amphotericin B lipid complex (Abelcet) in the prophylaxis of invasive fungal infections following lung transplantation. Transplant Proc. 2008; 40:3090-3. [PubMed 19010204]

462. Monforte V, Ussetti P, López R et al. Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant. 2009; 28:170-5. [PubMed 19201343]

463. Monforte V, Roman A, Gavalda J et al. Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant. 2001; 20:1274-81. [PubMed 11744410]

464. Monforte V, Ussetti P, Gavaldà J et al. Feasibility, tolerability, and outcomes of nebulized liposomal amphotericin B for Aspergillus infection prevention in lung transplantation. J Heart Lung Transplant. 2010; 29:523-30. [PubMed 20061165]

465. Herbrecht R, Letscher-Bru V, Bowden RA et al. Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis. 2001; 20:460-6. [PubMed 11561801]

466. Kauffman CA, Vazquez JA, Sobel JD et al. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000; 30:14-8. [PubMed 10619726]

467. Nesbit SA, Katz LE, McClain BW et al. Comparison of two concentrations of amphotericin B bladder irrigation in the treatment of funguria in patients with indwelling urinary catheters. Am J Health Syst Pharm. 1999; 56:872-5. [PubMed 10344610]

468. Gubbins PO, McConnell SA, Penzak SR. Current management of funguria. Am J Health Syst Pharm. 1999; 56:1929-35; quiz 1936. [PubMed 10554910]

469. Drew RH, Arthur RR, Perfect JR. Is it time to abandon the use of amphotericin B bladder irrigation?. Clin Infect Dis. 2005; 40:1465-70. [PubMed 15844069]

470. Trinh T, Simonian J, Vigil S et al. Continuous versus intermittent bladder irrigation of amphotericin B for the treatment of candiduria. J Urol. 1995; 154:2032-4. [PubMed 7500451]

471. Sanford JP. The enigma of candiduria: evolution of bladder irrigation with amphotericin B for management--from Anecdote to Dogma and a lesson from Machiavelli. Clin Infect Dis. 1993; 16:145-7. [PubMed 8448292]

472. Jacobs LG, Skidmore EA, Cardoso LA et al. Bladder irrigation with amphotericin B for treatment of fungal urinary tract infections. Clin Infect Dis. 1994; 18:313-8. [PubMed 8011810]

473. Tuon FF, Amato VS, Penteado Filho SR. Bladder irrigation with amphotericin B and fungal urinary tract infection--systematic review with meta-analysis. Int J Infect Dis. 2009; 13:701-6. [PubMed 19155184]

474. Wise GJ. Do not abandon amphotericin B as an antifungal bladder irrigant. Clin Infect Dis. 2005; 41:1073-4; author reply 1074. [PubMed 16142684]

475. Kfoury AG, Smith JC, Farhoud HH et al. Adjuvant intrapleural amphotericin B therapy for pulmonary mucormycosis in a cardiac allograft recipient. Clin Transplant. 1997; 11:608-12. [PubMed 9408694]

476. Centers for Disease Control and Prevention (CDC). Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a single compounding pharmacy - United States, 2012. MMWR Morb Mortal Wkly Rep. 2012; 61:839-42. [PubMed 23076093]

477. Centers for Disease Control and Prevention. Multistate fungal meningitis outbreak investigation. From CDC website. Accessed 2013 Aug 12.

478. Centers for Disease Control and Prevention. Exserohilum rostratum. From CDC website. Accessed 2013 Aug 12.

479. Food and Drug Administration. Multistate outbreak of fungal meningitis and other infections. 2012 Dec 12. From FDA website. Accessed 2013 Aug 12.

480. da Cunha KC, Sutton DA, Gené J et al. Molecular identification and in vitro response to antifungal drugs of clinical isolates of exserohilum. Antimicrob Agents Chemother. 2012; 56:4951-4. [PubMed 22733074]

481. DoctorFungus.org. The Official Website of the Mycoses Study Group. Exserohilum spp. From doctorfungus website. Accessed 2012 Oct 16.

482. Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Microbiol Rev. 2010; 23:884-928. [PubMed 20930077]

483. Centers for Disease Control and Prevention (CDC). Spinal and paraspinal infections associated with contaminated methylprednisolone acetate injections - Michigan, 2012-2013. MMWR Morb Mortal Wkly Rep. 2013; 62:377-81. [PubMed 23677044]

484. Centers for Disease Control and Prevention. Interim treatment guidance for central nervous system and parameningeal infections associated with injection of contaminated steroid products. From CDC website. Accessed 2013 Aug 12.

485. Centers for Disease Control and Prevention. Interim treatment guidance for osteoarticular infections associated with injection of contaminated steroid products. From CDC website. Accessed 2013 Aug 12.

486. Centers for Disease Control and Prevention. Notice to clinicians: continued vigilance urged for fungal infections among patients who received contaminated steroid injections. From cdc website. Accessed 2013 Aug 12.

487. Adler A, Yaniv I, Samra Z et al. Exserohilum: an emerging human pathogen. Eur J Clin Microbiol Infect Dis. 2006; 25:247-53. [PubMed 16511679]

488. Ritter JM, Muehlenbachs A, Blau DM et al. Exserohilum Infections Associated with Contaminated Steroid Injections: A Clinicopathologic Review of 40 Cases. Am J Pathol. 2013; :.

489. Pappas PG, Kontoyiannis DP, Perfect JR et al. Real-time treatment guidelines: considerations during the Exserohilum rostratum outbreak in the United States. Antimicrob Agents Chemother. 2013; 57:1573-6. [PubMed 23384532]

490. Kerkering TM, Grifasi ML, Baffoe-Bonnie AW et al. Early clinical observations in prospectively followed patients with fungal meningitis related to contaminated epidural steroid injections. Ann Intern Med. 2013; 158:154-61. [PubMed 23183583]

491. Smith RM, Schaefer MK, Kainer MA et al. Fungal Infections Associated with Contaminated Methylprednisolone Injections - Preliminary Report. N Engl J Med. 2012; :.

492. Kainer MA, Reagan DR, Nguyen DB et al. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012; 367:2194-203. [PubMed 23131029]

b. AHFS Drug Information 2010. McEvoy GK, ed. Amphotericin B. Bethesda, MD: American Society of Health-System Pharmacists; 2010:555-66.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:90-101.

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