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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination beta-lactam/beta-lactamase inhibitor antibiotic. Piperacillin provides broad-spectrum coverage, and tazobactam protects against resistant bacteria that produce beta-lactamases.
## Primary Indications
- Hospital-acquired pneumonia (including ventilator-associated)
- Intra-abdominal infections
- Complicated skin and soft-tissue infections
- Febrile neutropenia (often in combination)
- Complicated urinary tract infections
## Adult Dosing
- **Usual dose:** 3.375 g (piperacillin 3 g + tazobactam 0.375 g) IV every 6 hours
- **Nosocomial pneumonia:** 4.5 g IV every 6 hours
- **Extended infusion (critically ill):** 3.375–4.5 g IV over 3–4 hours every 6–8 hours (local protocol dependent)
- **Maximum:** 18 g piperacillin per day (4.5 g x 4 doses)
## Pediatric Dosing
**For children ≥40 kg:** follow adult dosing.
**For children <40 kg (1 month–12 years):**
- Standard: 100 mg piperacillin/kg/dose IV every 8 hours
- Severe infections (e.g., cystic fibrosis, pseudomonal): 100 mg/kg/dose IV every 6 hours
- Maximum single dose: 4.5 g (piperacillin 4 g + tazobactam 0.5 g)
**Neonates (<1 month):** Dosing varies by gestational age and postnatal age; consult neonatal protocols.
## Dose Adjustments
Adjust for renal impairment based on creatinine clearance (CrCl):
- **CrCl 20–40 mL/min:** 3.375 g IV every 8 hours
- **CrCl <20 mL/min:** 2.25 g IV every 8 hours
- **Hemodialysis:** 2.25 g IV every 8 hours, give after dialysis
- **Continuous renal replacement therapy:** depends on modality and effluent rate; consult local protocols
No adjustment for hepatic impairment.
## Contraindications
- Known hypersensitivity to penicillins, cephalosporins, or beta-lactamase inhibitors
- Severe anaphylactic reaction to any beta-lactam (relative contraindication)
## Adverse Effects
- **Common:** diarrhea (including *C. difficile*), nausea, headache, rash, phlebitis at IV site
- **Serious:** anaphylaxis, severe skin reactions (SJS/TEN), acute interstitial nephritis, hemolytic anemia, seizures (high doses/renal failure), bleeding (antiplatelet effect due to beta-lactam)
## Key Drug Interactions
- **Warfarin:** increased INR/bleeding risk (monitor)
- **Methotrexate:** reduced clearance, increased toxicity
- **Vancomycin:** synergistic (used in febrile neutropenia); additive nephrotoxicity
- **Probenecid:** decreases renal excretion of piperacillin, increase levels
- **Vecuronium/neuromuscular blockers:** prolonged neuromuscular blockade
## Monitoring
- Renal function (baseline and regularly)
- Complete blood count (especially platelets and WBCs)
- Signs of bleeding, diarrhea, or hypersensitivity
- Serum drug levels not routinely recommended
- For long courses: monitor for superinfection
## Clinical Pearls
- Extended infusion (over 3–4 hours) may improve outcomes in critically ill patients with high MIC pathogens (local protocol dependent)
- In penicillin allergy, give with caution; cross-reactivity with cephalosporins is low (~1–2%)
- Piperacillin has a high sodium content (≈2.35 mEq/g) – relevant in patients with fluid/electrolyte restrictions
- Use combination therapy (e.g., with an aminoglycoside) in febrile neutropenia or serious pseudomonal infections
- Reversible bone marrow suppression (especially neutropenia) can occur with prolonged courses (>14 days)
**Disclaimer:** This information is for educational purposes and does not replace clinical judgment. Always verify doses and protocols against local guidelines and the individual patient’s clinical status, especially for pediatric, neonatal, and renally impaired populations.
