Sulfadiazine

Class: Sulfonamides
VA Class: AM650
Chemical Name: N1-2-pyrimidinylsulfanilamide
Molecular Formula: C10H10N4O2S
CAS Number: 68-35-9

Introduction

Antibacterial; intermediate-acting sulfonamide.a b c

Uses for Sulfadiazine

Prevention of Rheumatic Fever Recurrence

Alternative for prevention of recurrence (secondary prophylaxis) of rheumatic fever.118 126 c

AHA and AAP recommend long-term (continuous) secondary prophylaxis in patients who have been treated for documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.118 126

IM penicillin G benzathine is the drug of choice for secondary prophylaxis of rheumatic fever; oral penicillin V and oral sulfadiazine are alternatives.118 126

Do not use sulfadiazine for treatment of Streptococcus pyogenes (group A β-hemolytic streptococci) infections, including pharyngitis and tonsillitis.118 126 c Sulfadiazine will not eradicate S. pyogenes.126 c

Toxoplasmosis

Treatment of toxoplasmosis caused by Toxoplasma gondii, including encephalitis, retinochoroiditis, and congenital toxoplasmosis.108 114 115 116 117 118 c e f Designated an orphan drug by FDA for treatment of toxoplasmosis.

Sulfadiazine used in conjunction with pyrimethamine and leucovorin is the regimen of choice for treatment of toxoplasmosis in adults, adolescents, or children, including HIV-infected individuals.108 118 e f

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Sulfadiazine used in conjunction with atovaquone is one of several alternative regimens for treatment of toxoplasmosis in HIV-infected adults or adolescents when the regimen of choice cannot be used;e this regimen not studied for treatment of toxoplasmosis in children.f

Sulfadiazine used in conjunction with pyrimethamine and leucovorin is the regimen of choice for treatment of symptomatic or asymptomatic congenital toxoplasmosis.118 f Empiric treatment of the infant should be strongly considered if the mother had symptomatic Toxoplasma infection during pregnancy, even if the mother was treated.f

Sulfadiazine used in conjunction with pyrimethamine and leucovorin is the regimen of choice for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent relapse of T. gondii encephalitis in HIV-infected adults, adolescents, or children who have completed treatment for the disease.124 e f

Acute Otitis Media (AOM)

Has been used in conjunction with penicillin or erythromycin for treatment of AOM caused by susceptible Haemophilus influenzae.b c

Chancroid

Has been used for treatment of chancroid caused by H. ducreyi.b c Not included in CDC recommendations for treatment of chancroid.i

Chlamydial Infections

Has been used for treatment of inclusion conjunctivitis caused by Chlamydia trachomatis.c Oral or IV erythromycin usually is drug of choice; oral sulfonamides are alternatives (except in neonates).118 g

Has been used for treatment of trachoma caused by C. trachomatis.c Oral azithromycin may be the drug of choice for treatment of ocular trachoma; prolonged treatment with combined oral and topical anti-infectives (e.g., erythromycin, tetracyclines, sulfonamides) also has been used.118 g

Haemophilus influenzae Infections

Has been used for treatment of meningitis caused by H. influenzae; used in conjunction with another suitable anti-infective (e.g., streptomycin).c

Malaria

Has been used as an adjunct in the treatment of malaria caused by chloroquine- resistant Plasmodium falciparum.c Not a preferred or alternative agent for treatment of malaria.108

Neisseria meningitidis Infections

Has been used to eliminate meningococci from the nasopharynx of asymptomatic Neisseria meningitidis carriers and for chemoprophylaxis in close contacts of individuals with invasive meningococcal disease when the organism is known to be susceptible to sulfonamides.a b c Not a drug of choice; CDC and AAP recommend use of rifampin, ciprofloxacin, or ceftriaxone for chemoprophylaxis of meningococcal disease.118 h

Nocardia Infections

Has been used for treatment of nocardiosis.a b c

Sulfonamides (usually co-trimoxazole) are treatment of choice for most Nocardia infections.118 g Some experts suggest that sulfonamides that are less urine soluble (e.g., sulfadiazine) should be avoided.118

Plague

Has been used for treatment of plague caused by Yersinia pestis.j

Not considered a preferred or alternative agent for treatment of plague;g j sulfonamides appear to be less effective than other anti-infectives used in the treatment of plague (e.g., streptomycin, tetracycline, doxycycline).j

Urinary Tract Infections (UTIs)

Has been used for treatment of UTIs (e.g., pyelonephritis, pyelitis, cystitis) in the absence of obstructive uropathy or foreign bodies.b c

Use only when UTIs are caused by susceptible Escherichia coli, Klebsiella, Enterobacter, Staphylococcus aureus, Proteus mirabilis, or P. vulgaris and only when other more soluble sulfonamides have been ineffective.b c

Sulfadiazine Dosage and Administration

Administration

Oral Administration

Administer orally with a full glass (250 mL) of water.a c

Maintain adequate fluid intake during therapy to minimize risk of crystalluria and stone formation.a b c

Dosage

Individualize dosage according to the severity of the infection, the pharmacokinetics of sulfadiazine, and the response and tolerance of the patient.b

Pediatric Patients

General Pediatric Dosage
Oral

Infants and children ≥2 months of age: Manufacturer recommends 75 mg/kg or 2 g/m2 initially, followed by 150 mg/kg or 4 g/m2 daily given in 4–6 equally divided doses.c

AAP recommends 100–150 mg/kg daily given in 4 divided doses for the treatment of mild to moderate infections or 120–150 mg/kg daily given in 4–6 divided doses for the treatment of severe infections.118

Prevention of Rheumatic Fever Recurrence
Oral

Infants and children ≥2 months of age: Manufacturer recommends 500 mg once daily in those weighing <30 kg or 1 g once daily in those weighing >30 kg.c

AHA and AAP recommend 500 mg once daily in those weighing ≤27 kg or 1 g once daily in those weighing >27 kg.118 126

Long-term, continuous prophylaxis required.118 126 (See Table in Adult Dosage: Prevention of Rheumatic Fever Recurrence under Dosage and Administration.)

Toxoplasmosis
Treatment of Congenital Toxoplasmosis
Oral

50 mg/kg twice daily used in conjunction with oral pyrimethamine (2 mg/kg once daily for 2 days, then 1 mg/kg once daily for 2–6 months, then 1 mg/kg 3 times weekly) and oral or IM leucovorin (10 mg with each pyrimethamine dose).f

Optimal duration of treatment is unclear and should be determined in consultation with an expert; treatment often is continued for 12 months.118 f

Treatment in HIV-infected Infants and Children
Oral

25–50 mg/kg (up to 1–1.5 g) 4 times daily used in conjunction with oral pyrimethamine (2 mg/kg once daily for 3 days, then 1 mg/kg once daily) and oral leucovorin (10–25 mg once daily).f

Continue acute treatment for ≥6 weeks; a longer duration may be appropriate if disease is extensive or response incomplete at 6 weeks.f

Treatment in HIV-infected Adolescents
Oral

1 g every 6 hours in those weighing <60 kg or 1.5 g every 6 hours in those weighing ≥60 kg used in conjunction with oral pyrimethamine (200 mg once, then 50 mg once daily in those weighing <60 kg or 75 mg once daily in those weighing ≥60 kg) and oral leucovorin (at least 10–20 mg once daily).e

Alternatively, 1–1.5 g every 6 hours used in conjunction with oral atovaquone (1.5 mg twice daily).e

Continue acute treatment for ≥6 weeks; a longer duration may be appropriate if disease is extensive or response incomplete at 6 weeks.e

Prevention of Recurrence (Secondary Prophylaxis) in HIV-infected Infants and Children
Oral

85–120 mg/kg daily in 2–4 divided doses used in conjunction with oral pyrimethamine (1 mg/kg or 15 mg/m2 daily [up to 25 mg]) and oral leucovorin (5 mg once every 3 days).124

Secondary prophylaxis against toxoplasmosis generally is continued for life.124 e f The safety of discontinuing secondary toxoplasmosis prophylaxis in HIV-infected infants and children receiving potent antiretroviral therapy has not been extensively studied.124 e f

Prevention of Recurrence (Secondary Prophylaxis) in HIV-infected Adolescents
Oral

Dosage for secondary prophylaxis against toxoplasmosis in adolescents and criteria for initiation or discontinuance of such prophylaxis in this age group are the same as those recommended for adults.124 e (See Adult Dosage under Dosage and Administration.)

Neisseria meningitidis Infections
Treatment of Asymptomatic Meningococcal Carriers or Prophylaxis in Contacts
Oral

Children 2–12 months of age: 500 mg once daily for 2 days.a

Children 1–12 years of age: 500 mg twice daily for 2 days.a

Adults

General Adult Dosage
Oral

2–4 g initially, followed by 2–4 g daily in 3–6 equally divided doses.c

Prevention of Rheumatic Fever Recurrence
Oral

Adults weighing >30 kg: Manufacturer recommends 1 g once daily.c

Adults weighing >27 kg: AHA and AAP recommend 1 g once daily.118 126

Long-term, continuous prophylaxis required.118 126 (See Table.)

Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence

Patient Category

Duration

Rheumatic fever without carditis

5 years or until 21 years of age, whichever is longer118 126

Rheumatic fever with carditis but no residual heart disease (no valvular disease)

10 years or well into adulthood, whichever is longer118 126

Rheumatic fever with carditis and residual heart disease (persistent valvular disease)

At least 10 years since last episode and at least until 40 years of age; sometimes for life118 126

Toxoplasmosis
Treatment in HIV-infected Adults
Oral

1 g every 6 hours in those weighing <60 kg or 1.5 g every 6 hours in those weighing ≥60 kg used in conjunction with oral pyrimethamine (200 mg once, then 50 mg once daily in those weighing <60 kg or 75 mg once daily in those weighing ≥60 kg) and oral leucovorin (at least 10–20 mg once daily).e

Alternatively, 1–1.5 g every 6 hours used in conjunction with oral atovaquone (1.5 mg twice daily).e

Continue acute treatment for ≥6 weeks; a longer duration may be appropriate if disease is extensive or response incomplete at 6 weeks.e

Prevention of Recurrence (Secondary Prophylaxis) in HIV-infected Adults
Oral

0.5–1 g every 6 hours used in conjunction with oral pyrimethamine (25–50 mg daily) and oral leucovorin (10–25 mg once daily).124 e

Initiate long-term suppressive therapy or chronic maintenance therapy (secondary prophylaxis) in all patients who have completed initial treatment of toxoplasmosis encephalitis (TE).124 e

Consideration can be given to discontinuing secondary prophylaxis in adults or adolescents who successfully completed initial treatment for TE, are asymptomatic with respect to TE, and have a sustained (≥6 months) increase in CD4+ T-cell counts to >200/mm3.124 e

Reinitiate secondary prophylaxis if CD4+ T-cell count decreases to <200/mm3.124 e

Neisseria meningitis Infections
Treatment of Asymptomatic Meningococcal Carriers or Prophylaxis in Contacts
Oral

1 g twice daily for 2 days.a

Nocardiosis
Oral

4–8 g daily for a minimum of 6 weeks.a Continue for several months after apparent cure to prevent relapse.a

Prescribing Limits

Pediatric Patients

General Pediatric Dosage
Oral

Maximum 6 g daily.c

Toxoplasmosis
Treatment in HIV-infected Infants and Children
Oral

Maximum 1–1.5 g per dose.f

Special Populations

No special population dosage recommendations at this time.c

Cautions for Sulfadiazine

Contraindications

  • Hypersensitivity to sulfonamidesc or other chemically related drugs (e.g., sulfonylureas, thiazides).b

  • Infants <2 months of age (except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis).c (See Toxoplasmosis under Uses.)

  • Pregnancy at term.c d

  • Nursing women.c

  • Porphyria.b

Warnings/Precautions

Warnings

Severe Reactions

Severe (sometimes fatal) reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, have been reported with sulfonamides.b c

Sore throat, fever, pallor, purpura, or jaundice may be early indications of serious reactions.c

Discontinue sulfadiazine at the first appearance of rash or any sign of adverse reactions.b

Sensitivity Reactions

Hypersensitivity Reactions

Deaths associated with sulfonamide hypersensitivity reactions have been reported.c

Serum sickness syndrome or serum sickness-like reactions (e.g., fever, chills, rigors, flushing, joint pain, urticarial eruptions, conjunctivitis, bronchospasm, leukopenia) reported with sulfonamides.b

Various dermatologic reactions, including rash, pruritus, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyell’s syndrome (may be associated with corneal damage), Behcet’s syndrome, toxic epidermal necrolysis, and exfoliative dermatitis, reported in patients receiving sulfonamides.b

Photosensitivity has been reported.b

Incidence of hypersensitivity reactions appears to increase with increased sulfonamide dosage.b

Use with caution in patients with severe allergy or bronchial asthma.c

If a hypersensitivity reaction occurs during sulfonamide therapy, immediately discontinue the drug.b

Desensitization

Desensitization to sulfadiazine has been performed when use of the drug for the treatment of toxoplasmosis was considered necessary in HIV-infected patients who had a history of sulfadiazine hypersensitivity.

Consult specialized references for specific information on desensitization procedures and dosage.

Cross-sensitivity

Although cross-sensitization has been reported to occur between the various anti-infective sulfonamides, some diuretics such as acetazolamide and the thiazides, some goitrogens, and sulfonylurea antidiabetic agents,c the association between hypersensitivity to sulfonamide anti-infectives and subsequent sensitivity reactions to non-anti-infective sulfonamides (e.g., thiazides, sulfonylurea antidiabetic agents, furosemide, dapsone, probenecid) appears to result from a predisposition to allergic reactions in general rather than to cross-sensitivity to the sulfa moiety per se.

General Precautions

Renal Effects

Sulfonamides have been associated with renal toxicity manifested by renal colic, nephritis, urolithiasis, toxic nephrosis with anuria and oliguria, hematuria, proteinuria, crystalluria, kidney stone formation, and elevation of BUN and serum creatinine concentrations.b Nephritis and hemolytic-uremic syndrome also have been reported.b

Adverse renal effects usually are the result of crystalluria.b Risk of crystalluria may be decreased by maintaining an adequate urinary output and by increasing urinary pH.b Unless the urine is highly acidic and/or the drug is relatively insoluble, alkalinization of the urine usually is not necessary if urinary output is maintained at a minimum of 1.5 L daily.b

Perform urinalysis and assess kidney function frequently during sulfonamide therapy.b Maintain adequate fluid intake to minimize risk of crystalluria and stone formation.b c

If persistent, heavy crystalluria, hematuria, or oliguria occurs, sulfonamide therapy should be discontinued and alkali therapy maintained.b

Patients with G6PD Deficiency

Hemolysis may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency; this effect may be dose-related.b c

Laboratory Monitoring

Perform CBCs frequently during sulfadiazine therapy.c

Perform urinalysis (with careful microscopic examination) frequently during sulfadiazine therapy, especially in patients with impaired renal function.c

Considerable interindividual variations in sulfadiazine plasma concentrations occur with a given dosage.c Measure sulfadiazine blood concentrations in patients being treated for serious infections.c Free sulfonamide concentrations of 5–15 mg/100 mL may be considered therapeutically effective for most infections; concentrations of 12–15 mg/100 mL may be considered optimal for serious infections.c Do not exceed total blood concentrations of 20 mg/100 mL since adverse reactions occur more frequently above this level.c

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of sulfadiazine and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.b

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.b c Consider that in vitro susceptibility tests are not always reliable for sulfonamides.c If the patient is already taking sulfonamides, ensure that follow-up cultures have aminobenzoic acid added to the culture media.c

Specific Populations

Pregnancy

Category C.c

Contraindicated in pregnant women at term.c d May increase risk of neonatal hyperbilirubinemia and kernicterus.e

Lactation

Contraindicated in nursing women;c discontinue drug or nursing.c Distributed into milk; may cause kernicterus in the infant.c

Pediatric Use

Avoid use in infants <2 months of age (except when considered necessary for adjunctive use with pyrimethamine for the treatment of congenital toxoplasmosis).b c (See Toxoplasmosis under Uses.)

Kernicterus, caused by displacement of bilirubin from protein binding sites, has occurred in neonates treated with sulfonamides.b c

Hepatic Impairment

Use with caution in patients with impaired hepatic function.c

Renal Impairment

Use with caution in patients with impaired renal function.c (See Renal Effects under Cautions.)

Common Adverse Effects

GI effects (anorexia, nausea, vomiting, abdominal pain), headache, peripheral neuritis, fever, rash, pancreatitis, stomatitis, depression.c

Interactions for Sulfadiazine

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral (warfarin)

Possibility that sulfonamides may potentiate the effects of coumarin anticoagulants by displacing them from their protein-binding sites or by impairing anticoagulant metabolismb c

Closely monitor PT or INRb

Antidiabetic agents, sulfonylureas (chlorpropamide, tolbutamide)

Sulfonamides may potentiate the hypoglycemic effects by displacing the antidiabetic agents from their protein-binding sitesb c

Use with cautionb

Digoxin

Possible decreased GI absorption of digoxinb

If used concomitantly, monitor to ensure adequate digoxin concentrations b

Methotrexate

Possibility that sulfonamides may potentiate the effects of methotrexate by displacing it from protein-binding sitesb c

Use with cautionb

Probenecid

May displace sulfonamides from plasma albumin and increase concentrations of free drug in plasmac

NSAIAs (indomethacin)

May displace sulfonamides from plasma albumin and increase concentrations of free drug in plasmab c

Observe patient for possible adverse effectsb

Salicylates

May displace sulfonamides from plasma albumin and increase concentrations of free drug in plasmab c

Thiazide diuretics

Sulfonamides may potentiate the diuretic effects by displacing thiazide diuretics from their protein-binding sitesc

Uricosuric agents

Sulfonamides may potentiate the effects of uricosuric agents by displacing the agents from their protein-binding sitesc

Sulfadiazine Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract.a c

Peak plasma concentrations are attained within 3–7 hours.b c Considerable interindividual variations in plasma sulfadiazine concentrations occur with a given dosage.c

Exists in blood as free, conjugated, and protein-bound drug; only the free form is microbiologically active.c

Distribution

Extent

Distributed into most body tissues; appears to freely cross cell membranes.a

Distributed into CSF.c Free and total CSF concentrations may reach 32–65 and 40–60% of concurrent blood concentrations, respectively.c Higher sulfonamide CSF concentrations may be reached if meninges are inflamed.a

Crosses the placenta.c

Distributed into milk.c

Plasma Protein Binding

38–48%.c

Elimination

Metabolism

Liver; undergoes N4-acetylation (up to 40%).b

Elimination Route

Excreted principally in urine in the N4-acetylated form (about 15–40%) and unchanged (about 43–60%).a c Approximately 50% of a single dose is excreted in the urine within 24 hours; 60–85% can be recovered within 72 hours.a c

Half-life

About 7–17 hours.b

Stability

Storage

Oral

Tablets

20–25°C in tight, light resistant container.c

Actions and Spectrum

  • Competitively inhibits bacterial synthesis of folic acid (pteroylglutamic acid) from aminobenzoic acid.c

  • Bacteriostatic in action.c

  • Inhibits only microorganisms that synthesize their own folic acid.b Animal cells and bacteria capable of utilizing folic acid precursors or preformed folic acid are resistant to sulfonamides.b

Advice to Patients

  • Advise patients to drink a full glass of water (250 mL) with each dose and at frequent intervals throughout the day to prevent crystalluria and stone formation.c

  • Importance of reporting the occurrence of sore throat, fever, pallor, purpura, or jaundice to a clinician since this may indicate a serious blood disorder.c

  • Advise patients that photosensitivity has been reported with sulfonamides and they should avoid exposure to UV light or prolonged exposure to sunlight.b

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

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

  • Importance of advising patients of other important precautionary information.c (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

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

500 mg*

Tablets (with povidone)

Sandoz

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

SulfADIAZINE 500MG Tablets (SANDOZ): 30/$79.99 or 90/$205.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2008. 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

108. Anon. Drugs for parasitic infections. Med Lett Drugs Ther. Aug 2004. From the Medical Letter website ().

114. Dannemann B, McCutchan A, Israelski D et al. Treatment of toxoplasmic encephalitis in patients with AIDS: a randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann Intern Med. 1992; 116:33-43. [IDIS 289401] [PubMed 1727093]

115. Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327:1643-8. [IDIS 305877] [PubMed 1359410]

116. Protocol for use of sulfadiazine in persons with toxoplasmosis. Atlanta, GA: US Centers for Disease Control and Prevention; 1993 Feb 1.

117. Centers for Disease Control and Prevention, Atlanta, GA: Personal communication.

118. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

121. Centers for Disease Control and Prevention. Update: availability of sulfadiazine—United States. MMWR Morb Mortal Wkly Rep. 1994; 43:671. [IDIS 335152] [PubMed 8072481]

124. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons with human immunodeficiency virus. From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

126. Dajani A, Taubert K, Ferrieri P et al and the American Heart Association Committee on Rheumatic Fever et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Pediatrics. 1995; 96:758-64. [IDIS 355409] [PubMed 7567345]

127. Kaplan J, Centers for Disease Control and Prevention: Personal communication.

a. AHFS Drug Information 2007. McEvoy GK, ed. Sulfadiazine. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 418-9.

b. AHFS Drug Information 2007. McEvoy GK, ed. Sulfonamides General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:406-10.

c. Sandoz Inc. Sulfadiazine tablets prescribing information. Princeton, NJ. 2006 Jun.

d. Sandoz Inc. Princeton, NJ: Personal communication.

e. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-15):1-112.

f. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-14):1-92.

g. Anon. Choice of antibacterial drugs Med Lett Treat Guidel. 2004; 13-26.

h. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005; 54(RR-7):1-21.

i. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-96.

j. Inglesby TV, Dennis DT, Henderson DA for the Working Group on Civilian Biodefense. Plague as a biological weapon: medical and public health management. JAMA. 2000; 283:2281–90.

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