ceftazidime (Rx)

1-10%

Transient increases in transaminases (3-9%)

Eosinophilia (<7%)

Diarrhea (<2%)

Immune hypersensitivity reaction (2%)

Phlebitis (<2%)

Rash (maculopapular or erythematous) (2%)

Thrombocytosis (2%)

Injection site pain (1%)

<1%

Abdominal pain

Agranulocytosis

Angioedema

Asterixis

Coma

Dizziness

Encephalopathy

Fever

Hallucinations

Increased serum concentrations of bilirubin

Leukopenia

Lymphocytosis

Metallic taste

Myoclonia

Nausea or vomiting

Neuromuscular excitability

Neutropenia

Paresthesia

Photosensitivity

Pruritus

Seizures

Thrombocytopenia

Transient increases in blood urea nitrogen (BUN) or serum creatinine

Urticaria

Contraindications

Documented hypersensitivity to drug or excipients, or to cephalosporin class of antibacterial drugs, penicillins or other beta-lactam antibacterial drugs

Cautions

High and prolonged serum ceftazidime concentrations can occur from usual dosages in patients with transient or persistent reduction of urinary output because of renal insufficiency; elevated levels of the drug in these patients can lead to, seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonus reported in patients treated with ceftazidime; adjust dosing based on creatinine clearance in patients with renal impairment

Elevated international normalized ratio (INR) has reported in patients with nutritional deficiency, prolonged treatment, or renal or hepatic disease

Use with caution in patients with history of seizure disorder (especially in renal impairment, where drug levels may increase significantly)

Modify dose in renal impairment

Use with caution in patients with history of penicillin allergy

Prescribing the drug in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Clostridioides difficile-associated diarrhea

• Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftazidime products, and may range in severity from mild diarrhea to fatal colitis; treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile
• C. difficile produces toxins A and B, which contribute to the development of CDAD; hypertoxin- producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
• CDAD must be considered in all patients who present with diarrhea following antibacterial use; careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents
• If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated

Pregnancy category: B

Lactation: Drug excreted in breast milk; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Third-generation cephalosporin with broad-spectrum gram-negative activity, including Pseudomonas; has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms; arrests bacterial growth by binding to 1 or more penicillin-binding proteins, thereby, in turn, inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis

Absorption

Peak plasma time: IM, 1 hr

Distribution

Widely distributed to body tissues and fluids, including aqueous humor, ascitic and prostatic fluids, and bone; penetrates CSF when meninges are inflamed

Protein bound: 5-24%

Metabolism

Not metabolized

Elimination

Half-life: 1-2 hr

Dialyzable: Hemodialysis, yes; peritoneal dialysis, yes

Excretion: Urine (80-90% as unchanged drug)

IV Incompatibilities

Additive: Amikacin, aminophylline, ciprofloxacin, gentamicin, ranitidine

Y-site: Amiodarone, amphotericin B cholesteryl complex, azithromycin, amsacrine, clarithromycin, cisatracurium(?), doxorubicin liposome, erythromycin lactobionate, fluconazole(?), idarubucin, midazolam, nicardipine (incompatible at ceftazidime 125 mg/mL but compatible at ceftazidime 10 mg/mL), pentamidine, propofol (incompatible at ceftazidime 125 mg/mL but compatible at ceftazidime 40 mg/mL), sagramostim(?), vancomycin(?), warfarin

IV/IM Administration

IV

• Direct injection: Inject over 3-5 minutes directly into vein or through tubing of running compatible infusion solution
• Infusion: Infuse intermittently over 15-30 minutes

IM

• Inject deeply

Storage

Store intact vials at room temperature, protected from light