Zavicefta

Approved Indications:

• Lower Respiratory Tract Infections: Including hospital-acquired and community-acquired pneumonia caused by susceptible Gram-negative organisms.
• Urinary Tract Infections (UTIs): Both complicated and uncomplicated UTIs.
• Skin and Soft Tissue Infections: Especially those involving Gram-negative pathogens.
• Intra-abdominal Infections: Such as peritonitis, appendicitis, and infected pancreatic necrosis.
• Central Nervous System Infections: Including bacterial meningitis caused by susceptible strains of Pseudomonas aeruginosa, Neisseria meningitidis, and Haemophilus influenzae.
• Septicemia: Caused by susceptible Gram-negative organisms.
• Bone and Joint Infections: Including osteomyelitis and septic arthritis.
• Gynecologic Infections: Such as endometritis and pelvic inflammatory disease.
• Empirical Therapy in Febrile Neutropenia: As monotherapy or in combination for broad-spectrum coverage.

Off-label / Clinically Accepted Uses:

• Treatment of Multidrug-resistant Gram-negative infections, including Pseudomonas aeruginosa.
• Prophylaxis in surgical procedures, particularly urologic and abdominal operations in high-risk patients.

Adults:

• Usual Dose: 1–2 g IV every 8 hours.
• Severe Infections (e.g., septicemia, meningitis): 2 g IV every 8 hours.
• Hospital-acquired pneumonia or febrile neutropenia: 2 g IV every 8 hours.

Pediatrics:

• 1 month to 12 years: 30–50 mg/kg IV every 8 hours (max 6 g/day).
• Neonates (<1 month): 30 mg/kg IV every 12 hours initially, adjusted based on renal function.

Elderly:

• Use adult dosing but adjust based on renal function.

Renal Impairment:

• Dose must be reduced depending on creatinine clearance (CrCl):
• CrCl 30–50 mL/min: 1 g every 12 hours
• CrCl 16–29 mL/min: 1 g every 24 hours
• CrCl ≤15 mL/min: 500 mg every 24–48 hours
• Hemodialysis: 500 mg every 24 hours, plus supplemental dose after dialysis.

Route of Administration:

• Administer intravenously as a slow injection or infusion over 15–30 minutes.

Duration:

• Typically 7–14 days depending on infection type and severity.

Ceftazidime is a third-generation cephalosporin that exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to specific penicillin-binding proteins (PBPs), particularly PBP-3 in Gram-negative organisms, disrupting peptidoglycan cross-linking in the bacterial cell wall. This leads to lysis and death of the bacteria. It has high activity against Pseudomonas aeruginosa and Enterobacteriaceae, making it valuable in treating resistant infections.

• Absorption: Not orally bioavailable; administered parenterally.
• Distribution: Widely distributed into body tissues and fluids, including cerebrospinal fluid (especially during meningitis).
• Protein Binding: 10–20%
• Metabolism: Not significantly metabolized.
• Half-life: ~1.8–2.0 hours (prolonged in renal impairment)
• Elimination: Primarily excreted unchanged in urine via glomerular filtration.
• Bioavailability: 100% (IV).
• Peak Plasma Levels: Within 30–60 minutes after IV administration.

• Pregnancy: Category B
• Animal studies have not demonstrated harm, and there are no adequate human studies. Use only if clearly needed.
• Lactation:
• Excreted in small amounts in breast milk.
• Generally considered compatible with breastfeeding, but observe for GI disturbances or oral thrush in the infant.
• Caution advised in neonates due to immature renal function.

• Primary Class: Third-generation cephalosporin antibiotic
• Subclass: Beta-lactam antibiotic
• Spectrum: Broad-spectrum, especially potent against Gram-negative organisms including Pseudomonas aeruginosa

• Hypersensitivity to ceftazidime, other cephalosporins, or beta-lactam antibiotics
• Severe hypersensitivity (e.g., anaphylaxis) to penicillins
• Previous severe allergic reaction to any beta-lactam antibiotics

• Hypersensitivity Reactions: Use cautiously in patients with penicillin allergy; cross-reactivity risk exists.
• Clostridioides difficile-associated diarrhea: Can occur and be severe.
• Renal Impairment: Requires dose adjustment to prevent accumulation and neurotoxicity.
• Neurotoxicity: Risk of encephalopathy, seizures, especially in renal dysfunction.
• Superinfection: Prolonged use may result in overgrowth of non-susceptible organisms, including fungi.
• Prothrombin Time Prolongation: Monitor coagulation in at-risk patients.
• Neutropenia and Eosinophilia: Have been reported with prolonged use.

Common (≥1%)

• Gastrointestinal: Diarrhea, nausea, abdominal pain
• Skin: Rash, pruritus
• Hematologic: Eosinophilia, thrombocytosis
• Injection Site: Phlebitis, pain, inflammation

Serious / Rare

• Hypersensitivity: Anaphylaxis, Stevens-Johnson syndrome
• CNS: Seizures, encephalopathy, confusion (especially in renal impairment)
• Hematologic: Leukopenia, neutropenia, hemolytic anemia
• Hepatic: Elevated liver enzymes
• Renal: Interstitial nephritis (rare)

Timing:

• Most side effects occur during therapy or shortly after administration. Neurotoxicity is more likely with prolonged therapy or renal dysfunction.

• Aminoglycosides: Increased risk of nephrotoxicity when co-administered.
• Loop Diuretics (e.g., furosemide): May potentiate renal adverse effects.
• Chloramphenicol: Antagonistic in vitro; avoid co-administration.
• Probenecid: May alter renal excretion; generally not co-administered.
• Live Vaccines (e.g., typhoid oral): Antibiotics may reduce effectiveness.

Enzyme System:

• Not a substrate, inhibitor, or inducer of CYP450 enzymes—low risk of metabolic drug interactions.

• Revised dosing guidance in renal impairment in the latest IDSA guidelines.
• Expanded use in multidrug-resistant Gram-negative infections in critical care settings.
• New data support combination use with beta-lactamase inhibitors in resistant infections (e.g., ceftazidime/avibactam).

• Powder for Injection (Vials):
• Store below 25°C, protected from light.
• Reconstituted solution should be used within 12 hours at room temperature or within 24 hours if refrigerated (2°C–8°C).
• Premixed IV Bags:
• Store refrigerated at 2°C to 8°C.
• Do not freeze.
• Handling: Shake well after reconstitution; inspect for particulate matter before use.
• Light Sensitivity: Protect solutions from light during storage and administration.