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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Bacterial infections including *Pseudomonas aeruginosa*
## Adult Dosing
* **Complicated intra-abdominal infections, complicated skin and skin-structure infections, community-acquired pneumonia, nosocomial pneumonia:** 3.375 grams every 6 hours or 4.5 grams every 8 hours intravenously.
* **Severe infections with *Pseudomonas aeruginosa*:** May consider higher doses or more frequent administration, guided by clinical response and susceptibility testing.
* **Maximum dose:** Generally 4.5 grams every 6 hours.
## Pediatric Dosing
* **Intra-abdominal infections (when used in combination therapy), Skin and skin-structure infections:**
* 3 months to < 1 year: 50 mg piperacillin/6.25 mg tazobactam per kg intravenously every 6 hours.
* 1 to 12 years: 100 mg piperacillin/12.5 mg tazobactam per kg intravenously every 8 hours.
* **Nosocomial pneumonia:**
* 3 months to < 1 year: 75 mg piperacillin/9.375 mg tazobactam per kg intravenously every 6 hours.
* 1 to 12 years: 150 mg piperacillin/18.75 mg tazobactam per kg intravenously every 8 hours.
* **Maximum pediatric doses:** Do not exceed the adult maximum dose of 4.5 grams per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 33-50% and increase dosing interval to every 8 hours (adults).
* **Renal Impairment (CrCl 20-50 mL/min):** Increase dosing interval to every 8 hours (adults).
* **Hepatic Impairment:** No specific dose adjustment recommended, but use with caution.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of severe allergic reaction (e.g., anaphylaxis) to penicillins, cephalosporins, or other beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, elevated liver enzymes (AST, ALT).
* **Serious:** Anaphylaxis, *Clostridioides difficile*-associated diarrhea, seizures (rare, particularly with high doses or renal impairment), interstitial nephritis, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Aminoglycosides:** In vitro antagonism with *Pseudomonas aeruginosa*. Consider separate administration.
* **Neuromuscular blocking agents:** May prolong the effect of neuromuscular blocking agents.
* **Warfarin:** May decrease INR. Monitor INR closely.
## Monitoring
* Signs and symptoms of infection.
* Renal function (especially in patients with pre-existing renal disease or receiving concomitant nephrotoxic agents).
* Liver function tests.
* Hematologic parameters (CBC with differential and platelets), especially with prolonged therapy.
* Signs of hypersensitivity reactions.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against *Pseudomonas aeruginosa* and many Gram-negative anaerobes.
* The tazobactam component protects piperacillin from degradation by many beta-lactamases.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours when refrigerated. Refer to specific manufacturer guidelines for preparation and storage.
* Dosing in critically ill patients may require consideration of altered pharmacokinetics; consult institutional guidelines.
**Disclaimer:** This information is intended for healthcare professionals. Always refer to the official prescribing information and consult with appropriate resources to verify current dosing and safety guidelines before administering any medication.
