Zosyn
Zosyn
Generic Name
Zosyn
Brand Names
for the *combination antibiotic* piperacillin/tazobactam, used widely for severe bacterial infections.
Mechanism
- Piperacillin: A β‑lactam that interferes with bacterial cell‑wall synthesis by binding to penicillin‑binding proteins (PBPs), disrupting peptidoglycan cross‑linking.
- Tazobactam: A β‑lactamase inhibitor that protects piperacillin from enzymatic degradation by many β‑lactamases (including class A, C, and some class D).
- The combination provides a broad spectrum covering *Gram‑positive, Gram‑negative, anaerobes*, and many β‑lactamase‑producing organisms.
Pharmacokinetics
- Route: Intravenous (parenteral) only.
- Absorption: Complete with IV administration.
- Distribution: Volume of distribution ≈ 30 mL/kg; penetrates peritoneal fluid, CSF, and wound exudate.
- Metabolism: Minimal hepatic metabolism.
- Excretion: Renally cleared; half‑life 1 – 2 h (piperacillin) and 1 – 2 h (tazobactam).
- Dose Adjustment: Renal impairment → reduce dose or prolong interval; no adjustment for hepatic dysfunction.
Indications
- Complicated intra‑abdominal infections (e.g., peritonitis, appendicitis).
- Complicated skin and soft‑tissue infections (e.g., surgical wounds, necrotizing fasciitis).
- Pyelonephritis and other urinary tract infections (excluding uncomplicated cystitis).
- Meningitis (bacterial) when gram‑negative coverage is required.
- Bacteremia and septic shock where broad coverage is essential.
- Often used empirically pending culture results.
Contraindications
- Allergy to β‑lactams (penicillins, cephalosporins) or tazobactam.
- Severe hepatic impairment (not contraindicated but monitor liver function).
- Risk of C. difficile colitis: monitor for diarrhea, consider stool PCR if severe.
- Pregnancy: Category B; assume low risk but use if benefits outweigh risks.
- Pediatric use: Approved for ages ≥ 1 month; adjust dose according to weight and renal function.
Dosing
| Population | Dose | Frequency | Notes |
| Adults (normal renal function) | 3.375 g (piperacillin 3 g / tazobactam 0.375 g) IV | q6 h (12 h in patients > 70 kg) | 30‑min infusion |
| Adults (CrCl ≥ 30 mL/min) | 3.375 g q6 h | ||
| Adults (CrCl < 30 mL/min) | 1.125 g q6 h | Reduced dose | |
| Pediatrics (≥ 1 month) | 3.375 g/m² IV | q6 h | Based on BSA; adjust for renal function |
| Pediatrics (CrCl < 30 mL/min) | 1.125 g/m² IV | q6 h | Reduced dose |
• Ensure adequate infusion duration (30 min) to achieve therapeutic levels.
• In renal impairment, extend the dosing interval (e.g., q8 h) if necessary.
Adverse Effects
- Common: Nausea, vomiting, diarrhea, mild rash, transient leukopenia.
- Serious: Anaphylaxis, severe neutropenia, hemolytic uremic syndrome (rare), Clostridioides difficile colitis.
- Laboratory: Monitor CBC, LFTs, and creatinine periodically.
Monitoring
- Renal Function: Serum creatinine, CrCl; adjust dose accordingly.
- Hematologic: CBC with differential—watch for neutropenia.
- Liver Function: ALT/AST; rare hepatotoxicity.
- Clinical: Monitor for signs of drug‑related hypersensitivity, especially anaphylaxis.
- Infection markers: Temperature, white‑blood‑cell count, and cultures as needed.
Clinical Pearls
- Pearl 1: In elderly patients (> 70 kg), a 12‑hour interval may be sufficient, reducing total drug exposure without compromising efficacy.
- Pearl 2: For patients with Stage 3–5 CKD, start at 1.125 g q6 h and consider extending to q8 h or using a 24‑hour infusion to maintain steady plasma concentrations.
- Pearl 3: The addition of tazobactam permits *once‑daily dosing* in certain surgical prophylaxis protocols, but ensure the use of a 30‑min infusion to sustain adequate levels.
- Pearl 4: Avoid combining Zosyn with other β‑lactam antibiotics that are induced by the same metabolic pathway to reduce the risk of resistance and drug interactions.
- Pearl 5: When therapy is prolonged (> 7 days), assess for *C. difficile* infection early—shorter courses (< 5 days) have a lower risk.
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• Key pharmacology terms: *piperacillin*, *tazobactam*, *β‑lactamase inhibitor*, *Gram‑negative coverage*, *renal impairment dosing*, *C. difficile colitis*.
This drug card offers a concise, evidence‑based overview suitable for rapid reference by medical students and healthcare professionals.