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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. It has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
Dosing is typically based on piperacillin content. Common regimens include:
* **3.375 g (3 g piperacillin/0.375 g tazobactam) every 6 hours**
* **4.5 g (4 g piperacillin/0.5 g tazobactam) every 6 or 8 hours**
The total daily dose of piperacillin should not exceed 18 g. Duration of therapy depends on the indication and clinical response. Extended-infusion regimens (e.g., 4-hour infusion of 4.5 g every 8 hours) may be considered for improved efficacy in certain settings.
## Pediatric Dosing
Dosing is typically based on piperacillin content. For children 2 months of age and older:
* **3.375 g/kg/day (3 g piperacillin/0.375 g tazobactam/kg/day) divided into 4 doses (given every 6 hours)**
* **Maximum daily dose: 18.75 g (16.67 g piperacillin/2.08 g tazobactam)**
Specific dosing may vary based on indication and institutional guidelines. Neonates and infants younger than 2 months require special consideration and may be dosed differently, often based on gestational age and postnatal age.
## Dose Adjustments
**Renal Impairment:** Adjust dose based on creatinine clearance (CrCl).
* CrCl 20-40 mL/min: Reduce dose by 25% or increase interval to every 8 hours.
* CrCl <20 mL/min: Reduce dose by 50% or increase interval to every 8-12 hours.
* Hemodialysis: Administer a dose after each dialysis session.
**Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain, fever, phlebitis.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin-tazobactam.
* **Aminoglycosides:** Concurrent use may lead to physical or chemical inactivation. If coadministration is necessary, administer separately. Avoid concurrent administration in certain settings (e.g., empiric treatment of VAP in patients with risk factors for *Pseudomonas aeruginosa*).
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Neuromuscular blocking agents:** May prolong the duration of neuromuscular blockade.
* **Methotrexate:** May decrease serum concentrations of methotrexate. Monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count (CBC) to monitor for hematologic changes (e.g., neutropenia, thrombocytopenia).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile* infection.
* Signs and symptoms of infection for therapeutic response.
## Clinical Pearls
* Piperacillin-tazobactam is often reconstituted with sterile water for injection and then further diluted in a compatible intravenous fluid (e.g., 0.9% sodium chloride, 5% dextrose).
* Extended infusion may improve outcomes and is often preferred for critically ill patients or those with infections caused by less susceptible organisms.
* Empirical use in suspected Gram-negative infections in patients with penicillin allergies should be carefully considered due to potential cross-reactivity, though cross-reactivity is less common than with earlier penicillins.
* The beta-lactamase inhibitor tazobactam extends the spectrum of piperacillin to include many beta-lactamase producing organisms, including some *Pseudomonas aeruginosa*.
**Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines for complete details.
