Zolibac

Approved Indications:

• Skin and Skin Structure Infections: Caused by susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and other streptococci.
• Urinary Tract Infections: Including acute and chronic pyelonephritis and cystitis due to E. coli, P. mirabilis, and some Klebsiella species.
• Respiratory Tract Infections: Particularly those caused by S. pneumoniae, K. pneumoniae, and H. influenzae (when proven susceptible).
• Bone and Joint Infections: Osteomyelitis and septic arthritis.
• Biliary Tract Infections: Including cholecystitis and cholangitis.
• Endocarditis: Caused by susceptible strains of staphylococci or streptococci (prophylactic and therapeutic use).
• Genital Infections: Including gonorrhea, prostatitis, and epididymitis.
• Septicemia: Due to gram-positive cocci and gram-negative rods susceptible to cefazolin.
• Perioperative Prophylaxis: To prevent postoperative infections in contaminated or potentially contaminated surgeries (e.g., gastrointestinal, orthopedic, gynecologic, and cardiovascular procedures).

Important Off-label Uses:

• Methicillin-sensitive Staphylococcus aureus (MSSA) Bacteremia
• Empiric therapy in suspected soft tissue or surgical wound infections
• Penicillin-allergic surgical prophylaxis (in non–immediate-type hypersensitivity)

Adults:

• Usual dose: 250 mg to 1 g IV or IM every 8 hours.
• Severe infections: Up to 6 g/day in divided doses, sometimes higher in life-threatening cases.
• Perioperative prophylaxis: 1–2 g IV within 60 minutes before incision, followed by intraoperative doses for prolonged surgeries.

Pediatric Patients:

• Dosage: 25–100 mg/kg/day IV or IM, divided every 6–8 hours.
• Severe infections: May increase to up to 150 mg/kg/day.

Neonates:

• 20–50 mg/kg/day IV, divided every 12 hours (premature or <1 week old) or every 8 hours (older neonates).

Elderly:

• Standard adult dosing may be used, but renal function must be monitored and dosage adjusted accordingly.

Renal Impairment:

• Dosage adjustment required:
• CrCl 10–30 mL/min: Give every 12 hours.
• CrCl <10 mL/min: Give every 24 hours.

Hepatic Impairment:

• No dosage adjustment typically required.

Administration:

• Administer via slow IV injection (3–5 minutes), IV infusion (over 30–60 minutes), or deep IM injection into large muscle mass.

Cefazolin Sodium is a first-generation cephalosporin that exerts its bactericidal activity by inhibiting bacterial cell wall synthesis. It binds specifically to penicillin-binding proteins (PBPs), particularly PBP-1 and PBP-3, located inside the bacterial cell wall. This inhibits the final transpeptidation step of peptidoglycan synthesis, weakening the cell wall, and resulting in cell lysis and death. It is most active against gram-positive cocci and limited gram-negative organisms.

• Absorption: Not absorbed orally; must be administered parenterally.
• Distribution: Widely distributed in body tissues and fluids including synovial fluid, pleural fluid, and bile. Limited CNS penetration unless meninges are inflamed.
• Protein Binding: ~80–85%
• Onset of Action: Rapid (within 1 hour IV)
• Peak Plasma Time: ~0.5–1 hour after IV/IM administration
• Half-life: ~1.8 hours in patients with normal renal function
• Metabolism: Not significantly metabolized
• Elimination: Primarily excreted unchanged in urine via glomerular filtration
• Excretion: ~80–100% within 24 hours

• Pregnancy: Category B (US FDA)
  No evidence of fetal harm in animal studies. Use only if clearly needed during pregnancy.
• Lactation:
  Cefazolin is excreted in low concentrations into breast milk. Generally considered safe during breastfeeding, but monitor infant for gastrointestinal disturbances or yeast infections.

• Primary Class: First-generation Cephalosporin Antibiotic
• Subclass: Beta-lactam, Bactericidal Agent

• Known hypersensitivity to cefazolin, other cephalosporins, or any formulation component
• History of severe anaphylactic reaction to penicillins (cross-reactivity possible)
• Intra-articular administration (not recommended due to potential for joint damage)

• Hypersensitivity Reactions: Serious anaphylaxis may occur, especially in patients with penicillin allergy.
• Clostridioides difficile-associated diarrhea (CDAD): Can range from mild to fatal colitis.
• Renal Impairment: Dose adjustment required to avoid accumulation and toxicity.
• Superinfection: Long-term use may lead to fungal or bacterial superinfection.
• Seizures: Possible with high doses or renal failure; monitor CNS effects.
• Monitoring: Renal function, signs of hypersensitivity, and gastrointestinal symptoms.

Common:

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain
• Injection Site: Pain, induration, phlebitis (with IV)
• Dermatologic: Rash, pruritus

Less Common:

• Hematologic: Eosinophilia, neutropenia, thrombocytopenia
• Hepatic: Transient elevations in liver enzymes (AST, ALT)
• Renal: Interstitial nephritis (rare)

Serious/Rare:

• Anaphylaxis
• Stevens-Johnson syndrome
• Seizures (especially in renal dysfunction)
• Pseudomembranous colitis

• Probenecid: Increases cefazolin serum levels by inhibiting renal excretion.
• Aminoglycosides: Concurrent use may increase nephrotoxicity risk.
• Loop diuretics: May enhance nephrotoxicity when used together.
• Oral anticoagulants (e.g., warfarin): Potentiation of anticoagulant effect may occur; monitor INR.
• Vaccines: May interfere with typhoid vaccine efficacy.

CYP450 Interaction: None – cefazolin is not metabolized by cytochrome P450 enzymes.

• IDSA Guidelines (Infectious Diseases Society of America) reaffirmed cefazolin as the preferred first-line agent for MSSA bacteremia due to superior tissue penetration and safety compared to anti-staphylococcal penicillins.
• Updates emphasize dose adjustments in renal impairment and perioperative prophylaxis timing.
• No changes in pregnancy/lactation recommendations or black box warnings noted as of 2025.

• Vials (powder for injection): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Reconstituted Solutions: Stable for up to 24 hours at room temperature or 10 days refrigerated (2°C to 8°C).
• IV Admixtures: Follow institutional policies; typically stable up to 24 hours at room temperature.
• Protection: Store in original container; protect from light and moisture.
• Do Not Freeze reconstituted solution.