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Ceftazidime

Pronunciation

Class: Third Generation Cephalosporins
Chemical Name: [6R-[6α,7β(Z)]]-1-[[7-[[(2-Amino-4-thiazolyl) [(1 - carboxy - 1 - methylethoxy)imino]acetyl]amino] - 2 - carboxy - 8 - oxo - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - en - 3 - yl]methyl] pyridinium hydroxide, inner salt, pentahydrate
CAS Number: 78436-06-2
Brands: Fortaz, Tazicef

Introduction

Antibacterial; β-lactam antibiotic; third generation cephalosporin.1 3 7 10 45 50 53 54 56 147 150 203 217

Uses for Ceftazidime

Bone and Joint Infections

Treatment of bone and joint infections caused by susceptible Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only) Klebsiella, or Pseudomonas aeruginosa.1 104 118 136 217 251 298

Intra-abdominal and Gynecologic Infections

Treatment of gynecologic infections (including endometritis, pelvic cellulitis, other infections of the female genital tract) caused by susceptible Escherichia coli.1 217 251

Treatment of intra-abdominal infections (including peritonitis) caused by susceptible S. aureus (oxacillin-susceptible strains only), E. coli, or Klebsiella.1 217 251

Treatment of polymicrobial intra-abdominal infections caused by susceptible aerobic and anaerobic bacteria and Bacteroides.1 136 137 217 251 Consider that many strains of B. fragilis are resistant; generally should not be used alone in serious intra-abdominal infections when this organism may be involved.1 217 251 a

For initial empiric treatment of high-risk or severe community-acquired extrabiliary intra-abdominal infections in adults, IDSA recommends either monotherapy with a carbapenem (doripenem, imipenem, meropenem) or the fixed combination of piperacillin and tazobactam, or a combination regimen that includes either a cephalosporin (cefepime, ceftazidime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.70

Meningitis and Other CNS Infections

Treatment of meningitis caused by susceptible H. influenzae, Neisseria meningitidis, Ps. aeruginosa, or Streptococcus pneumoniae in adults or children.1 46 47 50 137 217 251 254

Ceftazidime in conjunction with an aminoglycoside considered a regimen of choice for treatment of meningitis caused by susceptible P. aeruginosa13 14 112 147 197 337 354 or susceptible Enterobacteriaceae (e.g., E. coli, P. mirabilis, Enterobacter, S. marcescens).46 47 222 223 224 335

Cefotaxime or ceftriaxone generally preferred when a third generation cephalosporin is indicated for treatment of meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae.47 150 197 216 335 336 337 338

Respiratory Tract Infections

Treatment of respiratory tract infections (including pneumonia) caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains only), S. pneumoniae, Citrobacter, Enterobacter, E. coli, Klebsiella, Proteus mirabilis, Pseudomonas (including Ps. aeruginosa), or Serratia.1 103 108 117 118 119 120 137 143 144 146 147 148 217 251

Slideshow: Flashback: FDA Drug Approvals 2013

For treatment of community-acquired pneumonia (CAP) caused by Ps. aeruginosa, ATS and IDSA recommend a combination regimen that includes an antipseudomonal β-lactam (cefepime, ceftazidime, aztreonam, imipenem, meropenem, piperacillin, ticarcillin) given in conjunction with ciprofloxacin, levofloxacin, or an aminoglycoside.227

Septicemia

Treatment of septicemia caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains only), S. pneumoniae, Haemophilus influenzae, E. coli, Klebsiella, Ps. aeruginosa, or Serratia.1 115 118 119 120 146 217 251

Select anti-infective for treatment of sepsis syndrome based on probable source of infection, causative organism, immune status of patient, and local patterns of bacterial resistance.197

For initial treatment of life-threatening sepsis in adults, some clinicians suggest that a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftriaxone, ceftazidime), the fixed combination of piperacillin and tazobactam, or a carbapenem (doripenem, imipenem, meropenem) be used in conjunction with vancomycin; some also suggest including an aminoglycoside or fluoroquinolone during initial few days of treatment.197

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains only), S. pyogenes (group A β-hemolytic streptococci), Enterobacter, E. coli, Klebsiella, Proteus (including P. mirabilis), Ps. aeruginosa, or Serratia.1 115 118 119 120 136 146 217 251

Urinary Tract Infections (UTIs)

Treatment of uncomplicated and complicated UTIs caused by susceptible Enterobacter, E. coli, Klebsiella, Proteus (including P. mirabilis), Ps. aeruginosa, or Serratia.1 106 113 115 118 119 137 141 145 153 217

Burkholderia Infections

Treatment of septicemia or pulmonary infections caused by Burkholderia cepacia (formerly Ps. cepacia);147 197 208 345 alone or in conjunction with an aminoglycoside.147 197 208 345 Co-trimoxazole considered drug of choice; ceftazidime, chloramphenicol, or imipenem are alternatives.197

Treatment of melioidosis caused by B. pseudomallei (formerly Ps. pseudomallei).197 264 266 267 276 277 346 355 356 357 358 Usually treated with initial parenteral regimen of ceftazidime, imipenem, or meropenem (some clinicians recommend co-trimoxazole also be included, especially if patient is septicemic) followed by prolonged maintenance with oral anti-infectives (e.g., co-trimoxazole with or without doxycycline).275 355 356 357 358 B. pseudomallei is difficult to eradicate (relapse of melioidosis is common).264 266 276 346 355

Otitis Externa

Treatment of malignant otitis externa caused by Ps. aeruginosa.352 353

Acute bacterial otitis externa localized in the external auditory canal may be effectively treated using topical anti-infectives (e.g., otic preparations of ciprofloxacin or ofloxacin), but malignant otitis externa is an invasive, potentially life-threatening infection (especially in immunocompromised patients such as those with diabetes mellitus or HIV infection) and requires prompt diagnosis and long-term treatment with parenteral anti-infectives (e.g., ceftazidime and/or ciprofloxacin).352 353

Pseudomonas aeruginosa Infections

Generally considered a drug of choice for treatment of infections caused by Ps. aeruginosa,50 57 147 186 198 including acute exacerbations of bronchopulmonary Ps. aeruginosa infections in children and adults with cystic fibrosis.28 119 125 126 128 129 130 132 134 147 150 154 208 246 313 332 348

In severe infections, especially in immunocompromised patients, concomitant use of ceftazidime and an aminoglycoside (e.g., amikacin, gentamicin, tobramycin) is recommended.197 Consider that ceftazidime-resistant strains of Ps. aeruginosa can emerge during therapy and superinfection with resistant strains has occurred.50 111 115 147

Anti-infective therapy in patients with cystic fibrosis may result in clinical improvement and Ps. aeruginosa may be temporarily cleared from the sputum, but a bacteriologic cure is rarely obtained and should not be expected.28 119 125 126 132 149 150 208 246 313

Vibrio Infections

Treatment of infections caused by Vibrio vulnificus.219 256

Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.197 219 256 Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.256 262

Empiric Therapy in Febrile Neutropenic Patients

Has been used alone or in conjunction with an aminoglycoside for empiric treatment of presumed bacterial infections in febrile neutropenic adults or children.122 123 124 138 139 140 212 228 247 248 249 261 279 280 286 287 288 289 290 291 292 294 295 347 349

IDSA states that ceftazidime is no longer a reliable agent for empiric monotherapy in febrile neutropenic patients because of decreasing potency against gram-negative bacteria and poor activity against many gram-positive bacteria (e.g., streptococci).390

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.390 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.390

Perioperative Prophylaxis

Has been used for perioperative prophylaxis in patients undergoing vaginal hysterectomy,151 biliary or intra-abdominal surgery,167 169 or transurethral resection of the prostate.142

First or second generation cephalosporins (cefazolin, cefotetan, cefoxitin, cefuroxime) generally preferred when a cephalosporin used for perioperative prophylaxis.168 169 Third generation cephalosporins (cefotaxime, ceftriaxone, ceftazidime) and fourth generation cephalosporins (cefepime) not usually recommended for perioperative prophylaxis since they are expensive, some are less active against staphylococci than first or second generation cephalosporins, they have spectrums of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis may promote emergence of resistant organisms.168 169

Ceftazidime Dosage and Administration

Administration

Administer by intermittent IV injection or infusion or by deep IM injection.1 217 Also has been administered by continuous IV infusion.299 300 301 302 310 332 348

Has been administered intraperitoneally in dialysis solutions.1 27 217 Should not be administered by intra-arterial injection since necrosis can occur.1 217

IV route preferred for treatment of septicemia, meningitis, peritonitis, or other severe or life-threatening infections and in patients with lowered resistance resulting from malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.1 217

The commercially available frozen ceftazidime injection in dextrose should be used only for IV infusion.1

For solution and drug compatibility information, see Compatibility under Stability.

IV Injection

Reconstitution

For intermittent IV injection, reconstitute vials containing 500 mg, 1 g, or 2 g with 5.3 mL, 10, or 10 mL, respectively, of sterile water for injection to provide solutions containing approximately 100, 100, or 170 mg/mL, respectively.1 217

Shake vial after adding the diluent;1 217 carbon dioxide is released as drug dissolves and the solution will become clear within 1–2 minutes.1 217 When withdrawing a dose from reconstituted vials, consider that the solution may contain some carbon dioxide bubbles which should be expelled from the syringe before injection.1 217

Rate of Administration

Inject appropriate dose of reconstituted solution into a vein over a period of 3–5 minutes or slowly into the tubing of a compatible IV solution.1 217

IV Infusion

Reconstitution and Dilution

Reconstitute vials of containing 1 or 2 g of ceftazidime with 100 mL of sterile water for injection or compatible IV solution.1 217 Shake the vial after adding the diluent;1 217 carbon dioxide is released as the drug dissolves and the solution will become clear within 1–2 minutes.1 217 The appropriate dose of the drug should then be added to a compatible IV solution.1 217

Reconstitute pharmacy bulk packages according to the manufacturer’s directions and then further dilute in a compatible IV infusion solution prior to administration.1 233

ADD-Vantage or TwistVialvials labeled as containing 1 or 2 g of ceftazidime should be reconstituted according to the manufacturer’s directions.1 217

Reconstitute (activate) commercially available Duplex drug delivery system containing 1 or 2 g of ceftazidime and 50 mL of 5% dextrose injection in separate chambers according to the manufacturer's directions.251 If refrigerated after reconstitution (see Storage under Stability), allow solution to reach room temperature prior to administration.251

Thaw commercially available premixed injection (frozen) at room temperature (25°C) or under refrigeration (5°C); do not thaw by immersion in a water bath or by exposure to microwave radiation.1 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.1 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact or leaks are found.1 Do not use in series connections with other plastic containers; such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from secondary container is complete.1

Rate of Administration

Intermittent IV infusions generally have been infused over 15–30 minutes in adults,8 102 104 105 115 116 118 119 133 137 139 144 neonates,34 and children.108 157

If a Y-type administration set is used, the other solution flowing through the tubing should be discontinued while ceftazidime is being infused.1 217 262

IM Injection

IM injections should be made deeply into a large muscle mass, such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.1 217

Reconstitution

IM injections are prepared by adding 1.5 or 3 mL of sterile or bacteriostatic water for injection or 0.5 or 1% lidocaine hydrochloride injection to vials containing 500 mg or 1 g of ceftazidime, respectively, to provide solutions containing approximately 280 mg/mL.1

Shake the vial after adding the diluent;1 217 carbon dioxide is released as the drug dissolves and the solution will become clear within 1–2 minutes.1 217 When withdrawing a dose from reconstituted vials, consider that the solution may contain some carbon dioxide bubbles which should be expelled from the syringe before injection.1 217

Intraperitoneal Instillation

Reconstitute with sterile water for injection as for IV infusion221 and then further dilute in a compatible peritoneal dialysis solution to provide a solution containing 250 mg of ceftazidime in each 2 L of dialysis solution.1 217

Dosage

Available as ceftazidime pentahydrate and as ceftazidime sodium; dosage expressed as anhydrous ceftazidime.1 3 217

Do not use ceftazidime available in Duplex containers in patients who require less than entire 1- or 2-g dose in the container.251

Pediatric Patients

General Dosage for Neonates
IV

Neonates ≤4 weeks of age: Manufacturer recommends 30 mg/kg every 12 hours.1 217

Neonates ≤7 days of age: AAP recommends 50 mg/kg every 12 hours, regardless of weight.275

Neonates 8–28 days of age: AAP recommends 50 mg/kg every 8–12 hours in those weighing ≤2 kg and 50 mg/kg every 8 hours in those weighing >2 kg.275

General Dosage for Infants and Children 1 Month to 12 Years of Age
IV

25–50 mg/kg every 8 hours.1 38 103 107 217 254 Use 50 mg/kg every 8 hours in immunocompromised children or children with cystic fibrosis.1 28 30 108 126 128 129 149 217

Children beyond neonatal period: AAP recommends 90–150 mg/kg daily in 3 equally divided doses for the treatment of mild to moderate infections or 200–300 mg/kg daily in 3 equally divided doses for treatment of severe infections.275

General Dosage for Children >12 Years of Age
IV

Use usual adult dosage.1 217 (See Adult Dosage under Dosage and Administration.)

Meningitis
IV

Some clinicians recommend 100–150 mg/kg daily in 2 or 3 equally divided doses for neonates ≤7 days of age and 150 mg/kg daily in 3 divided doses in older neonates and children.354

Because of a high rate of relapse, treatment duration should be ≥3 weeks for meningitis caused by gram-negative bacilli.335 337 354 In neonates, some clinicians recommend that treatment be continued for 2 weeks beyond the first sterile CSF culture or at least 3 weeks, whichever is longer.354

Burkholderia Infections
Severe Melioidosis Caused by Burkholderia pseudomallei
IV

Children ≥2 months of age: 60 mg/kg daily in 2 equally divided doses recommended by some clinicians for children <2 months of age or 100 mg/kg daily in 3 equally divided doses.357 Concomitant co-trimoxazole or doxycycline may be indicated in septicemic or other severe cases.357

Continue initial parenteral regimen for at least 10–14 days and until there is clinical improvement.275 355 356 357 When appropriate, switch to oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continue for at least 3–6 months to prevent recrudence or relapse.275 355 356 357 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.356 357

Empiric Therapy in Febrile Neutropenic Children
IV

50 mg/kg (maximum 2 g) every 8 hours has been used in pediatric patients ≥2 years of age.347

Adults

General Adult Dosage
Less Severe Infections
IV or IM

1 g every 8–12 hours.1 217

Severe or Life-threatening Infections
IV

2 g every 8 hours,1 especially in immunocompromised patients.1

Bone and Joint Infections
IV

2 g every 12 hours.1 104 217

Intra-abdominal and Gynecologic Infections
Serious Infections
IV

2 g every 8 hours.1 217

Meningitis
IV

2 g every 8 hours.1 217 354 Duration of treatment is ≥3 weeks for meningitis caused by susceptible gram-negative bacilli.335 337 354

Respiratory Tract Infections
Uncomplicated Pneumonia
IV or IM

0.5–1 g every 8 hours.1 217

Pseudomonas Lung Infections in Cystic Fibrosis Patients
IV

30–50 mg/kg every 8 hours (up to 6 g daily).1 28 30 50 125 126 128 129 149 217 246 348

Clinical improvement may occur, but bacteriologic cures should not be expected in patients with chronic respiratory disease and cystic fibrosis.1 28 119 125 126 132 149 150 208 217

Skin and Skin Structure Infections
Mild Infections
IV or IM

0.5–1 g every 8 hours.1 104 217

Urinary Tract Infections (UTIs)
Uncomplicated Infections
IV or IM

250 mg every 12 hours.1 104 217

Complicated Infections
IV or IM

500 mg every 8–12 hours.1 104 217

Burkholderia Infections
Severe Melioidosis Caused by Burkholderia pseudomallei
IV

40 mg/kg every 8 hours recommended by US Army Medical Research Institute of Infectious Diseases (USAMRIID).356 Others recommend 2 g every 8 hours (up to 6 g daily)357 or 50 mg/kg (up to 2 g) every 6 hours.355 358 Concomitant co-trimoxazole or doxycycline may be indicated in septicemic or other severe cases.355 356 357 358

Continue initial parenteral regimen for at least 10–14 days and until there is clinical improvement.275 355 356 357 358 When appropriate, switch to an oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continue for at least 3–6 months to prevent recrudence or relapse.275 355 356 357 358 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.356 357

Empiric Therapy in Febrile Neutropenic Patients
IV

100 mg/kg daily in 3 divided doses or 2 g every 8 hours either alone or in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin) has been used.261 279 280 286 290 292 295 349

Prescribing Limits

Pediatric Patients

Maximum 6 g daily.1

Adults

Maximum 6 g daily.1 217 221 225

Special Populations

Hepatic Impairment

Dosage adjustments not required unless renal function also impaired.1 150 217

Renal Impairment

Reduce dosage in patients with Clcr ≤50 mL/minute.1 217

Manufacturers recommend that adults with Clcr ≤50 mL/minute receive an initial loading dose of 1 g and a maintenance dosage based on Clcr.1 217 (See Table.)

Maintenance Dosage for Adults with Renal Impairment1

Clcr (mL/minute)

Dosage

31–50

1 g every 12 h

16–30

1 g every 24 h

6–15

500 mg every 24 h

<5

500 mg every 48 h

Patients with renal impairment and severe infections who would generally receive 6 g daily if renal function were normal: increase dosage in table by 50% or dosing interval may be increased appropriately.1

Patients undergoing hemodialysis: given an initial loading dose of 1 g followed by 1 g after each hemodialysis period.1 217 221

Patients undergoing intraperitoneal dialysis or CAPD: given an initial loading dose of 1 g followed by 500 mg every 24 hours.1 217 221

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal function.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Ceftazidime

Contraindications

  • Known hypersensitivity to ceftazidime or other cephalosporins.1

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy.1 Careful observation of the patient is essential.1 217 Institute appropriate therapy if superinfection occurs.1 217

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including ceftazidime, and may range in severity from mild diarrhea to fatal colitis.1 217 340 341 342 C. difficile produces toxins A and B which contribute to development of CDAD;1 217 340 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1 217

Consider CDAD if diarrhea develops and manage accordingly.1 217 340 341 342 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1 217 340

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 217 340 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 217 340 341 342

Neurotoxicity

Possibility of seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia if inappropriately high dosage used in patients with renal impairment.1 (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.1 217 a

Hypersensitivity reactions, including anaphylaxis, reported with dextrose-containing solutions;251 usually reported in patients receiving high dextrose concentrations (i.e., 50% dextrose), but also reported when corn-derived dextrose solutions administered to patients with or without history of hypersensitivity to corn products.251

If an allergic reaction occurs, discontinue and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen).1 217

Cross-hypersensitivity

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1 217 a

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1 217 Cautious use recommended in individuals hypersensitive to penicillins:1 217 a avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.a

General Precautions

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis.1 217 (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Prolonged PT

Possibility of prolonged PT.1 217

Monitor PT in patients at risk, including those with renal or hepatic impairment, poor nutritional state, receiving prolonged therapy, or stabilized on anticoagulant therapy.1 217 Administer vitamin K when indicated.1 217

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftazidime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1 217

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 217 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 217

Resistance in Gram-negative Bacteria

Resistance caused by inducible type I β-lactamases can develop in some gram-negative bacilli (e.g., Enterobacter, Pseudomonas, Serratia) during treatment, leading to clinical failure in some cases.1

When treating infections caused by these bacteria, perform periodic in vitro susceptibility testing when clinically appropriate.1 If patient fails to respond to monotherapy, an aminoglycoside or similar agent should be considered.1

Risk of Distal Necrosis

Possibility of distal necrosis after inadvertent intra-arterial administration.1

Sodium Content

Vials, pharmacy bulk packages, and ADD-Vantage vials contain ceftazidime admixed with sodium carbonate to facilitate dissolution.1 217 233 These preparations contain approximately 54 mg (2.3 mEq) of sodium per g of ceftazidime.1 217 233

Patients with Diabetes

Like other dextrose-containing solutions, use Duplex drug delivery system containing ceftazidime and dextrose injection with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.251

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in low concentrations; use with caution.1

Pediatric Use

To avoid unintentional overdosage, do not use ceftazidime available in Duplex containers in pediatric patients who require less than entire 1- or 2-g dose in the container.251

Geriatric Use

No overall differences in safety and efficacy in those ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.1

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.1 Select dosage with caution and assess renal function periodically because of age-related decreases in renal function.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not affected.1

Renal Impairment

Possible decreased clearance and increased serum half-life.1

Neurotoxicity reported in some patients with renal impairment who received dosage inappropriately high for their renal status.1 (See Neurotoxicity under Cautions.)

Dosage adjustments necessary in patients with Clcr ≤50 mL/minute.1 See Renal Impairment under Dosage and Administration.

Common Adverse Effects

GI effects, hypersensitivity reactions, local reactions at IV injection sites.1

Interactions for Ceftazidime

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Aminoglycosides

Nephrotoxicity reported with concomitant use of some cephalosporins and aminoglycosides1 209 217

In vitro evidence of additive or synergistic antibacterial activity against Pseudomonas and Enterobacteriaceae1 50 63 90 147 186 187 191 217

Carefully monitor renal function, especially if high aminoglycoside dosage is used or if therapy is prolonged1 217

Chloramphenicol

In vitro evidence of antagonism against gram-negative bacilli1 270 271 272 273 274

Avoid concomitant use1 274

Probenecid

No appreciable effect on pharmacokinetics of ceftazidime1 5 10 24 50 130 147 164 217

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 173 a

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1 173 a

Ceftazidime Pharmacokinetics

Absorption

Bioavailability

Not absorbed from GI tract; must be given parenterally.3 50

Following IM administration, peak serum concentrations attained in approximately 1 hour.1 6 12 217 May be absorbed more slowly in women than in men following IM injection into the gluteus maximus or vastus lateralis.6 In women, peak serum concentrations may be lower following IM injection into the gluteus maximus than into the vastus lateralis.6

In patients with end-stage chronic renal failure who receive a single dose of the drug via an intraperitoneal catheter, peak serum concentrations attained 2.75 hours after the dose.27

Distribution

Extent

Widely distributed into body tissues and fluids including the gallbladder,24 234 255 bone,1 3 23 147 203 217 220 bile,1 3 10 11 18 24 49 50 147 203 217 255 skeletal muscle,1 3 23 50 203 217 234 prostatic tissue,21 217 234 endometrium,25 myometrium,1 3 25 217 234 heart,1 3 23 50 203 217 skin,1 3 23 50 217 234 adipose tissue,23 50 234 aqueous humor,1 3 16 22 147 203 217 and sputum,1 3 28 30 49 147 154 203 217 and pleural,22 203 peritoneal,1 3 15 50 166 167 217 synovial,1 3 217 ascitic,160 166 lymphatic,1 3 22 217 and blister1 3 22 165 217 fluids.

Generally diffuses into CSF following IV administration;1 11 13 19 20 22 50 147 158 217 223 224 226 CSF concentrations higher in patients with inflamed meninges than in those with uninflamed meninges.10 13 19 20 22 50 147 158

Distributed into bile, but biliary concentrations following IM or IV administration may be lower than concurrent serum concentrations.10 11 18 255

Crosses the placenta3 32 and is distributed into milk.1 3 17 203

Plasma Protein Binding

5–24%.1 4 6 8 10 11 50 147 203

Elimination

Metabolism

Not metabolized.1 3 4 9 10 11 12 24 50 217

Elimination Route

Eliminated unchanged principally in urine by glomerular filtration.1 3 7 10 11 24 47 50 203 217

80–90% of a dose eliminated in urine within 24 hours.1 12 24 161 165 203 217

Half-life

Adults with normal renal and hepatic function: distribution half-life 0.1–0.6 hours and elimination half-life 1.4–2 hours.1 4 5 6 7 24 36 161 166 203 217

Neonates: 2.2–4.7 hours.34 35 147 226

Children 1–12 months of age: 2 hours.155

Special Populations

Patients with impaired hepatic function: serum half-life only slightly prolonged.1 26 166 217

Patients with impaired renal function: serum concentrations higher and serum half-life prolonged.1 9 24 37 153 159 161 162 217 Serum half-life ranges from 9.4–10.3 hours in those with Clcr 13–27 mL/minute and 11–35 hours in those with Clcr<10 mL/minute.

Stability

Storage

Parenteral

Powder for Injection or IV Infusion

Fortaz: 15–30° C; protect from light.1 217

Fortaz: Reconstituted IV solutions containing 100, 170, or 200 mg/mL prepared using sterile water and IV solutions that have been further diluted to 1–40 mg/mL in a compatible IV solution are stable for 12 hours at room temperature or 3 days under refrigeration.1

Fortaz: Reconstituted IM solutions containing 280 mg/mL prepared using sterile or bacteriostatic water or 0.5 or 1% lidocaine hydrochloride are stable for 12 hours at room temperature or 3 days under refrigeration.1

Tazicef: 20–25°C; protect from light.217

Tazicef: Reconstituted IV or IM solutions containing 95, 180, or 280 mg/mL prepared using sterile water are stable for 24 hours at room temperature or 7 days when refrigerated.217

Powder for injection and solutions may darken; does not indicate loss of potency.1 217

For Injection, for IV Infusion

Fortaz TwistVial vials: 15–30°C; protect from light.1 After reconstitution, stable for 12 hours at room temperature or 3 days under refrigeration.1

Tazicef ADD-Vantage vials: 20–25°C; protect from light.217 After reconstitution, stable for 24 hours at room temperature.217

Duplex drug delivery system containing ceftazidime and dextrose injection: 20–25°C (may be exposed to 15–30°C);251 protect from light.251 After reconstitution (activation), use within 12 hours if stored at room temperature or within 3 days if stored in refrigerator; do not freeze. 251

Injection (Frozen) for Infusion

-20° C or lower.1 Thawed solution stable for 8 hours at room temperature or 3 days under refrigeration.1

Do not refreeze after thawing.1

Compatibility

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

Parenteral

Solution Compatibility

Less stable in sodium bicarbonate injection than in other IV solutions; sodium bicarbonate not recommended as a diluent.1

CompatibleHID

Amino acids 5%, dextrose 25%

Dextrose 5% in sodium chloride 0.2, 0.45, or 0.9%1

Dextrose 5 or 10% in water1

Invert sugar 10% in water1

Normosol M in dextrose 5%1

Ringer’s injection1

Ringer’s injection, lactated1

Sodium bicarbonate 4.2%

Sodium chloride 0.9%1

Sodium lactate (1/6) M1

Drug Compatibility
Admixture CompatibilityHID

Compatible

Clindamycin phosphate

Fluconazole

Heparin sodium

Linezolid

Metronidazole

Potassium chloride

Incompatible

Amikacin sulfate

Aminophylline

Gentamicin sulfate

Ranitidine HCl

Variable

Ciprofloxacin

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Amikacin sulfate

Aminophylline

Anidulafungin

Aztreonam

Bivalirudin

Ciprofloxacin

Daptomycin

Dexmedetomidine HCl

Diltiazem HCl

Docetaxel

Dopamine HCl

Doxapram HCl

Enalaprilat

Epinephrine HCl

Esmolol HCl

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Filgrastim

Fludarabine phosphate

Foscarnet sodium

Furosemide

Gallium nitrate

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Insulin, regular

Ketamine HCl

Labetalol HCl

Linezolid

Melphalan HCl

Meperidine HCl

Methylprednisolone sodium succinate

Milrinone lactate

Morphine sulfate

Ondansetron HCl

Paclitaxel

Ranitidine HCl

Remifentanil HCl

Sufentanil citrate

Tacrolimus

Telavancin HCl

Teniposide

Thiotepa

Tigecycline

Tobramycin sulfate

Valproate sodium

Vinorelbine tartrate

Zidovudine

Incompatible

Acetylcysteine

Amiodarone HCl

Amphotericin B cholesteryl sulfate complex

Azithromycin

Caspofungin acetate

Doxorubicin HCl liposome injection

Erythromycin lactobionate

Idarubicin HCl

Midazolam HCl

Pemetrexed disodium

Pentamidine isethionate

Phenytoin sodium

Warfarin sodium

Variable

Cisatracurium besylate

Dobutamine HCl

Fluconazole

Nicardipine HCl

Propofol

Sargramostim

Theophylline

Vancomycin HCl

Actions and Spectrum

  • Based on spectrum of activity, classified as a third generation cephalosporin.1 45 50 51 52 53 57 58 59 60 63 147 150 a Usually less active in vitro against susceptible staphylococci than first generation cephalosporins; has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.50 52 53 57 58 59 60 63 147 150 195 196 200 201 a

  • Usually bactericidal.1 50 52 55 56 95 147 150 217 a

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 3 50 150 217 230 a

  • Spectrum of activity includes many gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and some anaerobic bacteria; inactive against Chlamydia, fungi, and viruses.a

  • Spectrum of activity of ceftazidime resembles that of ceftizoxime, cefotaxime, and ceftriaxone.52 53 55 58 59 63 196 200 However, ceftazidime more active against Pseudomonas than most other currently available parenteral third generation cephalosporins50 52 53 54 55 56 58 59 60 62 150 195 196 200 201 and less active against anaerobes and gram-positive aerobic cocci than these drugs.50 52 53 55 58 60 195 196 200 201

  • Gram-positive aerobes: active in vitro and in clinical infections against S. aureus (including β-lactamase-producing strains), S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and S. agalactiae (group B streptococci).1 a Oxacillin-resistant (methicillin-resistant) staphylococci and enterococci (e.g., Enterococcus faecalis) are resistant.1 a

  • Gram-negative aerobes: active in vitro and in clinical infections against Citrobacter (including C. freundii, C. diversus), Enterobacter (including E. aerogenes, E. cloacae), E. coli, H. influenzae (including ampicillin-resistant strains), Klebsiella (including K. pneumoniae), Neisseria meningitidis, Proteus mirabilis, P. vulgaris, Pseudomonas (including Ps. aeruginosa), and Serratia.1 a Also active in vitro against Acinetobacter, H. parainfluenzae, Morganella morganii, N. gonorrhoeae, Providencia (including P. rettgeri), Salmonella, Shigella, and Yersinia enterocolitica.1

  • Anaerobes: active in vitro and in clinical infections against Bacteroides; many strains of B. fragilis are resistant.1 Also active in vitro against Clostridium (except C. difficile), Peptococcus, and Peptostreptococcus.1

  • Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to ceftazidime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.204

Advice to Patients

  • Advise patients that antibacterials (including ceftazidime) should only be used to treat bacterial infections; they do not treat viral infections (e.g., the common cold).1 217

  • Importance of completing full course of therapy, even if feeling better after a few days.1 217

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftazidime or other antibacterials in the future.1 217

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 217 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1 217

  • Importance of informing clinicians if an allergic reaction occurs.1 217

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1 217

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 217

  • Importance of informing patients of other important precautionary information.1 217 (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

Ceftazidime

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

equivalent to anhydrous ceftazidime 500 mg (with sodium carbonate)*

Ceftazidime for Injection

Fortaz

Covis

equivalent to anhydrous ceftazidime 1 g (with sodium carbonate)*

Ceftazidime for Injection

Fortaz

Covis

Tazicef

Hospira

equivalent to anhydrous ceftazidime 2 g (with sodium carbonate)*

Ceftazidime for Injection

Fortaz

Covis

Tazicef

Hospira

equivalent to anhydrous ceftazidime 6 g pharmacy bulk package (with sodium carbonate)*

Ceftazidime for Injection

Fortaz

Covis

Tazicef

Hospira

For injection, for IV infusion

equivalent to anhydrous ceftazidime 1 g (with sodium carbonate)

Ceftazidime for Injection (available in dual-chambered Duplex drug delivery system with 5% dextrose injection)

B Braun

Fortaz TwistVial

Covis

Tazicef ADD-Vantage

Hospira

equivalent to anhydrous ceftazidime 2 g (with sodium carbonate)

Ceftazidime for Injection (available in dual-chambered Duplex drug delivery system with 5% dextrose injection)

B Braun

Fortaz TwistVial

Covis

Tazicef ADD-Vantage

Hospira

Ceftazidime Sodium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

equivalent to 20 mg (of anhydrous ceftazidime) per mL (1 g) in 4.4% Dextrose

Fortaz Iso-osmotic in Dextrose Injection (Galaxy [Baxter])

Covis

equivalent to 40 mg (of anhydrous ceftazidime) per mL (2 g) in 3.2% Dextrose

Fortaz Iso-osmotic in Dextrose Injection (Galaxy [Baxter])

Covis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 10, 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

1. Covis Pharmaceuticals Inc. Fortaz (ceftazidime) powder for injection and injection prescribing information. Cary, SC; 2012 Apr.

3. Glaxo Inc. Product information form on Fortaz. Research Triangle Park, NC; 1985 Jan.

4. Kemmerich B, Warns H, Lode H et al. Multiple-dose pharmacokinetics of ceftazidime and its influence on fecal flora. Antimicrob Agents Chemother. 1983; 24:333-8. [IDIS 175796] [PubMed 6357074]

5. Luthy R, Blaser J, Bonetti A et al. Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime. Rev Infect Dis. 1982; 4(Suppl Nov-Dec):S581-4. [IDIS 161908] [PubMed 6296966]

6. Sommers DK, Walters L, Van Wyk M et al. Pharmacokinetics of ceftazidime in male and female volunteers. Antimicrob Agents Chemother. 1983; 23:892-6. [IDIS 172597] [PubMed 6351732]

7. Drusano GL, Standiford HC, Fitzpatrick B et al. Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers. Antimicrob Agents Chemother. 1984; 26:388-93. [IDIS 190368] [PubMed 6391372]

8. Warns H, Lode H, Harnoss CM et al. Multiple dose pharmacokinetics and therapeutic results with ceftazidime. J Antimicrob Chemother. 1983; 12(Suppl A):235-40. [PubMed 6352625]

9. Hoffler D, Koeppe P, Williams KJ. The pharmacokinetics of ceftazidime in normal and impaired renal function. J Antimicrob Chemother. 1983; 12(Suppl A):241-5. [PubMed 6352626]

10. Balant L, Dayer P, Auckenthaler R. Clinical pharmacokinetics of the third generation cephalosporins. Clin Pharmacokinet. 1985; 10:101-43. [IDIS 198911] [PubMed 3888488]

11. Noble JT, Barza M. Pharmacokinetic properties of the newer cephalosporins: a valid basis for drug selection? Drugs. 1985; 30:175-81.

12. Harding SM, Harper PB. The pharmacokinetic behaviour of ceftazidime in man and the relationship between serum levels and the in vitro susceptibility of clinical isolates. Infection. 1983; 11(Suppl 1):S49-53.

13. Alestig K, Olaison L, Rylander M. Ceftazidime for Pseudomonas meningitis. Lancet. 1985; 1:161-2. [PubMed 2857231]

14. Williams KJ. Ceftazidime for Pseudomonas meningitis. Lancet. 1985; 1:634. [IDIS 196875] [PubMed 2857964]

15. Wittman DH, Schassan HH. Penetration of eight β-lactam antibiotics into the peritoneal fluid: a pharmacokinetic investigation. Arch Surg. 1983; 118:205-13. [IDIS 166007] [PubMed 6849637]

16. Axelrod JL, Kochman RS, Horowitz MA et al. Ceftazidime concentrations in human aqueous humor. Arch Ophthalmol. 1984; 102:923-5. [IDIS 186293] [PubMed 6375645]

17. Blanco JD, Jorgensen JH, Castaneda YS et al. Ceftazidime levels in human breast milk. Antimicrob Agents Chemother. 1983; 23:479-80. [IDIS 167349] [PubMed 6342531]

18. Bouza E, Hellin T, Rodriguez-Creixems M et al. Comparison of ceftazidime concentrations in bile and serum. Antimicrob Agents Chemother. 1983; 24:104-6. [IDIS 173444] [PubMed 6414363]

19. Modai J, Vittecoq D, Decazes JM et al. Penetration of ceftazidime into cerebrospinal fluid of patients with bacterial meningitis. Antimicrob Agents Chemother. 1983; 24:126-8. [IDIS 173446] [PubMed 6354077]

20. Fong IW, Tomkins KB. Penetration of ceftazidime into the cerebrospinal fluid of patients with and without evidence of meningeal inflammation. Antimicrob Agents Chemother. 1984; 26:115-6. [IDIS 187637] [PubMed 6383206]

21. Abbas AM, Taylor MC, Da Silva C et al. Penetration of ceftazidime into the human prostate gland following intravenous injection. J Antimicrob Chemother. 1985; 15:119-21. [PubMed 3882653]

22. Walstad RA, Hellum KB, Blika S et al. Pharmacokinetics and tissue penetration of ceftazidime: studies on lymph, aqueous humour, skin blister, cerebrospinal and pleural fluid. J Antimicrob Chemother. 1983; 12(Suppl A):275-82. [PubMed 6352632]

23. Adam D, Reichart B, Williams KJ. Penetration of ceftazidime into human tissue in patients undergoing cardiac surgery. J Antimicrob Chemother. 1983; 12(Suppl A):269-73. [PubMed 6352630]

24. Saito A. Studies on absorption, distribution, metabolism and excretion of ceftazidime in Japan. J Antimicrob Chemother. 1983; 12(Suppl A):255-62. [PubMed 6352628]

25. Daschner FD, Petersen EE, Just HM et al. Penetration of ceftazidime into serum, myometrium, endometrium, salpinges and subcutaneous tissue. J Antimicrob Chemother. 1983; 12(Suppl A):247-9. [PubMed 6352627]

26. Pasko MT, Beam TR, Spooner JA et al. Safety and pharmacokinetics of ceftazidime in patients with chronic hepatic dysfunction. J Antimicrob Chemother. 1985; 15:365-74. [PubMed 3888944]

27. Tourkantonis A, Nicolaidis P. Pharmacokinetics of ceftazidime in patients undergoing peritoneal dialysis. J Antimicrob Chemother. 1983; 12(Suppl A):263-7. [PubMed 6352629]

28. Strandvik B, Malmborg AS, Alfredson H et al. Clinical results and pharmacokinetics of ceftazidime treatment in patients with cystic fibrosis. J Antimicrob Chemother. 1983; 12(Suppl A):283-7. [PubMed 6352633]

29. Drusano GL, Joshi J, Forrest A et al. Pharmacokinetics of ceftazidime, alone or in combination with piperacillin or tobramycin, in the sera of cancer patients. Antimicrob Agents Chemother. 1985; 27:605-7. [IDIS 198588] [PubMed 3890730]

30. Turner A, Pedler SJ, Carswell F et al. Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis. J Antimicrob Chemother. 1984; 14:521-7. [PubMed 6392281]

31. Garcia I, Fainstein V, Smith RG et al. Multiple-dose pharmacokinetics of ceftazidime in cancer patients. Antimicrob Agents Chemother. 1983; 24:141-4. [IDIS 174901] [PubMed 6357067]

32. Giamarellou H, Gazis J, Petrikkos G et al. A study of cefoxitin, moxalactam, and ceftazidime kinetics in pregnancy. Am J Obstet Gynecol. 1983; 147:914-9. [IDIS 179400] [PubMed 6359888]

33. Mulhall A, de Louvois J. The pharmacokinetics and safety of ceftazidime in the neonate. J Antimicrob Chemother. 1985; 15:97-103. [PubMed 3882658]

34. McCracken GH, Threlkeld N, Thomas ML. Pharmacokinetics of ceftazidime in newborn infants. Antimicrob Agents Chemother. 1984; 26:583-4. [IDIS 193537] [PubMed 6393862]

35. Boccazzi A, Rizzo M, Caccamo ML et al. Comparison of the concentrations of ceftazidime in the serum of newborn infants after intravenous and intramuscular administration. Antimicrob Agents Chemother. 1983; 24:955-6. [IDIS 179243] [PubMed 6362562]

36. Leeder JS, Spino M, Tesoro AM et al. High-pressure liquid chromatographic analysis of ceftazidime in serum and urine. Antimicrob Agents Chemother. 1983; 24:720-4. [IDIS 179028] [PubMed 6362554]

37. Alestig K, Trollfors B, Andersson R et al. Ceftazidime and renal function. J Antimicrob Chemother. 1984; 13:177-81. [PubMed 6423614]

38. Prinsloo JG, Delport SD, Moncrieff J et al. Pharmacokinetics of ceftazidime in premature, newborn and young infants. S Afr Med J. 1984; 65:809-11. [IDIS 188725] [PubMed 6374925]

39. Narang PK, Hunter JR. Is renal function the only determinant in the elimination of ceftazidime? Rev Infect Dis. 1984; 6:732-5. (IDIS 191149)

40. Kroll MH, Koch TR, Drusano G et al. Lack of interference with creatinine assays by four cephalosporin-like antibiotics. Am J Clin Pathol. 1984; 82:214-6. [IDIS 188979] [PubMed 6087652]

41. Guay DR, Meatherall RC, Macaulay PA. Interference of selected second- and third-generation cephalosporins with creatinine determination. Am J Hosp Pharm. 1983; 40:435-8. [IDIS 166846] [PubMed 6846351]

42. LeBel M, Paone RP, Lewis GP. Lack of interference of five new beta-lactam antibiotics with serum creatinine determination. Drug Intell Clin Pharm. 1983; 17:908-10. [IDIS 182429] [PubMed 6317326]

43. Mondorg AW, Heynold FT, Scherberich JE et al. Assessment of the nephrotoxic potential of ceftazidime and a ceftazidime/tobramycin combination in volunteers. Infection. 1983; 11(Suppl 1):S57-62. [PubMed 6131873]

44. Foord RD. Ceftazidime: aspects of efficacy and tolerance. J Antimicrob Chemother. 1983; 12(Suppl A):399-403. [PubMed 6352651]

45. Neu HC. Relation of structural properties of beta-lactam antibiotics to antibacterial activity. Am J Med. 1985; 79(Suppl 2A):2-13.

46. Rodriguez WJ, Khan WN, Gold B et al. Ceftazidime in the treatment of meningitis in infants and children over one month of age. Am J Med. 1985; 79(Suppl 2A):52-5. [IDIS 204118] [PubMed 3895918]

47. Norrby SR. Role of cephalosporins in the treatment of bacterial meningitis in adults: overview with special emphasis on ceftazidime. Am J Med. 1985; 79(Suppl 2A):56-61. [IDIS 204119] [PubMed 3895919]

48. Meyers BR. Comparative toxicities of third-generation cephalosporins. Am J Med. 1985; 79(Suppl 2A):96-103. [IDIS 204124] [PubMed 4025384]

49. Gozzard DI, Geddes AM, Farrell ID et al. Ceftazidime: a new extended-spectrum cephalosporin. Lancet. 1982; 1:1152-6. [IDIS 150434] [PubMed 6122940]

50. Richards DM, Brogden RN. Ceftazidime: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1985; 29:105-61. [IDIS 198204] [PubMed 3884319]

51. Garzone P, Lyon J, Yu VL. Third-generation and investigational cephalosporins: I. Structure-activity relationships and pharmacokinetic review. Drug Intell Clin Pharm. 1983; 17:507-15. [IDIS 173270] [PubMed 6347596]

52. Thornsberry C. Review of in vitro activity of third-generation cephalosporins and other newer beta-lactam antibiotics against clinically important bacteria. Am J Med. 1985; 79(Suppl 2A):14-30. [IDIS 204113] [PubMed 3927723]

53. Knothe H, Dette GA. The current state of cephalosporin antibiotics: microbiological aspects. Infection. 1983; 11(Suppl 1):S12-5. [PubMed 6601063]

54. Neu HC. Structure-activity relations of new β-lactam compounds and in vitro activity against common bacteria. Rev Infect Dis. 1983; 5(Suppl 2):S319-36. [IDIS 171036] [PubMed 6342103]

55. Jones RN, Barry AL, Thornsberry C et al. Ceftazidime, a pseudomonas-active cephalosporin: in vitro antimicrobial activity evaluation including recommendations for disc diffusion susceptibility tests. J Antimicrob Chemother. 1981; 8(Suppl B):187-211. [PubMed 19802985]

56. Harper PB. In vitro properties of ceftazidime, a highly active broad-spectrum cephalosporin with antipseudomonal activity. Clin Ther. 1984; 6:411-24. [PubMed 6432324]

57. Reeves DS, Holt HA, Bywater MJ. Comparative activity in vitro of ceftazidime and nine other antibacterial agents. Infection. 1983; 11(Suppl 1):S3-11. [PubMed 6339414]

58. Garzone P, Lyon J, Yu VL. Third-generation and investigational cephalosporins: II. Microbiologic review and clinical summaries. Drug Intell Clin Pharm. 1983; 17:615-22. [IDIS 174601] [PubMed 6311502]

59. Corser CA, Day GJ, Humble MW et al. Third-generation cephalosporins: comparative antibacterial activity against routine clinical isolates. N Z Med J. 1982; 95:414-6. [IDIS 156142] [PubMed 6810246]

60. Fass RJ. Comparative in vitro activities of third-generation cephalosporins. Arch Intern Med. 1983; 143:1743-5. [IDIS 175434] [PubMed 6615095]

61. Appelbaum PC, Tamim J, Pankuch GA et al. Susceptibility of 324 nonfermentative gram-negative rods to 6 cephalosporins and azthreonam. Chemotherapy. 1983; 29:337-44. [IDIS 175165] [PubMed 6311492]

62. Livermore DM, Williams RJ, Williams JD. Comparison of the β-lactamase stability and the in-vitro activity of cefoperazone, cefotaxime, cefsulodin, ceftazidime, moxalactam and ceftriaxone against Pseudomonas aeruginosa. J Antimicrob Chemother. 1981; 8:323-31.

63. Neu HC, Labthavikul P. Antibacterial activity and β-lactamase stability of ceftazidime, an aminothiazolyl cephalosporin potentially active against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1982; 21:11-8. (IDIS 143683)

64. Bustamante CI, Drusano GL, Tatem BA et al. Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984; 26:678-82. (IDIS 194078)

65. Eng RH, Smith SM, Cherubin C. Inoculum effect of new β-lactam antibiotics on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984; 26:42-7. (IDIS 187629).

66. Laethem YV, Lagast H, Klastersky J. Serum bactericidal activity of ceftazidime and cefoperazone alone or in combination with amikacin against Pseudomonas aeruginosa and Klebsiella pneumoniae. Antimicrob Agents Chemother. 1983; 23:435-9. (IDIS 167345)

67. Rudrik JT, Cavalieri SJ, Britt EM. In vitro activities of enoxacin and 17 other antimicrobial agents against multiply resistant, gram-negative bacteria. Antimicrob Agents Chemother. 1984; 26:97-100. [IDIS 187633] [PubMed 6591853]

68. Khan MY, Gruninger RP, Nelson SM et al. Comparative in vitro activity of cefodizime, ceftazidime, aztreonam, and other selected antimicrobial agents against Neisseria gonorrhoeae. Antimicrob Agents Chemother. 1983; 23:477-8. (IDIS 167348)

69. Goossens H, Vanhoof R, Grados O et al. Ceftazidime activity on multiresistant Salmonella. Lancet. 1982; 2:769-70. Letter. (IDIS 158994)

70. Solomkin JS, Mazuski JE, Bradley JS et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50:133-64. [PubMed 20034345]

71. Liebowitz LD, Ballard RC, Koornhof HJ. In vitro susceptibility and cross-resistance of South African isolates of Neisseria gonorrhoeae to 14 antimicrobial agents. Antimicrob Agents Chemother. 1982; 22:598-603. [IDIS 159404] [PubMed 6817704]

72. Hall WH, Opfer BJ. Influence of inoculum size on comparative susceptibilities of penicillinase-positive and -negative Neisseria gonorrhoeae to 31 antimicrobial agents. Antimicrob Agents Chemother. 1984; 26:192-5. [IDIS 189066] [PubMed 6435514]

73. Nasu M, Maskell JP, Williams RJ et al. In vitro activity of MK0787 (N-formimidoyl thienamycin) and other beta-lactam compounds against Bacteroides spp. Antimicrob Agents Chemother. 1981; 20:433-6. [IDIS 139332] [PubMed 6282191]

74. Jacobs MR, Kelly F, Speck WT. Susceptibility of group B streptococci to 16 β-lactam antibiotics, including new penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1982; 22:897-900. [IDIS 160709] [PubMed 6758692]

75. Scribner RK, Marks MI, Weber A et al. Yersinia enterocolitica: comparative in vitro activities of seven new β-lactam antibiotics. Antimicrob Agents Chemother. 1982; 22:140-1. [IDIS 153527] [PubMed 7125625]

76. Hornstein MJ, Jupeau AM, Scavizzi MR et al. In vitro susceptibilities of 126 clinical isolates of Yersinia enterocolitica to 21 β-lactam antibiotics. Antimicrob Agents Chemother. 1985; 27:806-11. [IDIS 200508] [PubMed 2990327]

77. Laferriere C, Marks MI, Welch DF. Effect of inoculum size on Haemophilus influenzae type b susceptibility to new and conventional antibiotics. Antimicrob Agents Chemother. 1983; 24:287-9. [IDIS 174917] [PubMed 6605716]

78. Goldstein EJ, Citron DM. Susceptibility of Eikenella corrodens to penicillin, apalcillin, and twelve new cephalosporins. Antimicrob Agents Chemother. 1984; 26:947-8. [IDIS 194045] [PubMed 6395802]

79. Piot P, Van Dyck E, Colaert J. In vitro activity of ceftazidime (GR 20263) and other β-lactam antibiotics against Haemophilus influenzae. Infection. 1983; 11(Suppl 1):S32-4.

80. Muytjens HL, Heessen FW. In vitro activities of thirteen β-lactam antibiotics against Chlamydia trachomatis. Antimicrob Agents Chemother. 1982; 22:520-1. (IDIS 157302)

81. Denys GA, Jerris RC, Swenson JM et al. Susceptibility of Propionibacterium acnes clinical isolates to 22 antimicrobial agents. Antimicrob Agents Chemother. 1983; 23:335-7. [IDIS 166100] [PubMed 6838191]

82. Chattopadhyay B, Hall I, Curnow SR. Ceftazidime (GR 20263), a new cephalosporin derivative with excellent activity against Pseudomonas and Enterobacteriaceae. J Antimicrob Chemother. 1981; 8:491-3. [PubMed 6801002]

83. Alvarez S, Jones M, Holtsclaw-Berk S et al. In vitro susceptibilities and β-lactamase production of 53 clinical isolates of Branhamella catarrhalis. Antimicrob Agents Chemother. 1985; 27:646-7. (IDIS 198592)

84. Greenwood D, Eley A. Comparative antipseudomonal activity of some newer β-lactam agents. Antimicrob Agents Chemother. 1982; 21:204-9. [IDIS 146648] [PubMed 6803664]

85. Smalley DL, Hansen VR, Baselski VS. Susceptibility of Pseudomonas paucimobilis to 24 antimicrobial agents. Antimicrob Agents Chemother. 1983; 23:161-2. [IDIS 164460] [PubMed 6600908]

86. Grimm H. Criteria for the assessment of susceptibility to ceftazidime using the disc diffusion procedure. Infection. 1983; 11(Suppl 1):S35-8. [PubMed 6339416]

87. Sykes RB, Bush K. Interaction of new cephalosporins with β-lactamases and β-lactamase-producing gram-negative bacilli. Rev Infect Dis. 1983; 5(Suppl 2):S356-66.

88. Simpson IN, Plested SJ, Harper PB. Investigation of the β-lactamase stability of ceftazidime and eight other new cephalosporin antibiotics. J Antimicrob Chemother. 1982; 9:357-68. [PubMed 7047482]

89. Van Landuyt HW, Denolf BL, Pyckavet M et al. The in vitro activity of ceftazidime against resistant clinical isolates. Infection. 1983; 11(Suppl 1):S23-7. [PubMed 6299967]

90. Hooton TM, Blair AD, Turck M et al. Synergism at clinically attainable concentrations of aminoglycoside and β-lactam antibiotics. Antimicrob Agents Chemother. 1984; 26:535-8. [IDIS 193530] [PubMed 6517544]

91. Wise R, Andres JM, Danks G. Comparison of in vitro activity of FCE 22101, a new penem, with those of other β-lactam antibiotics. Antimicrob Agents Chemother. 1983; 24:909-14. [IDIS 179237] [PubMed 6607032]

92. Muytjens HL, Van der Ros-Van de Repe J. Comparative activities of 13 β-lactam antibiotics. Antimicrob Agents Chemother. 1982; 21:925-34. [IDIS 151717] [PubMed 7114839]

93. Vuye A, Pijck J. In vitro antibacterial activity of BMY-28142, a new extended-spectrum cephalosporin. Antimicrob Agents Chemother. 1985; 27:574-7. [IDIS 198582] [PubMed 3859244]

94. Toda M, Arao N, Nohara C et al. In vitro studies on the antibacterial activities of YM-13115, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother. 1985; 27:565-9. [IDIS 198581] [PubMed 3890729]

95. Tsuji A, Maniatis A, Bertram MA et al. In vitro activity of BMY-28142 in comparison with those of other β-lactam antimicrobial agents. Antimicrob Agents Chemother. 1985; 27:515-9. [IDIS 198575] [PubMed 3839120]

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