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# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor.
## 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
* **Standard Dose:** 3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin / 0.5 g tazobactam) IV every 6 or 8 hours.
* **Severe Infections/Higher Doses:** Doses up to 4.5 g IV every 4 hours (for a total daily dose of 13.5 g) may be used in specific situations, such as severe infections or documented resistance. The optimal dosing regimen depends on local protocols and the specific pathogen(s).
* **Duration of Therapy:** Typically 7 to 14 days, depending on the indication and clinical response.
## Pediatric Dosing
* **Patients ≥ 12 years:** Dosing is the same as adults.
* **Patients < 12 years:**
* **Dose:** 100 mg piperacillin / 12.5 mg tazobactam per kg of ideal body weight per dose, administered IV every 6 hours.
* **Maximum Dose:** Not to exceed the adult dose of 4.5 g per dose.
* **Note:** For patients with cystic fibrosis or other severe infections, higher doses (e.g., 300 mg piperacillin / 3.75 mg tazobactam per kg per dose every 4 or 6 hours) may be utilized per institutional guidelines.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):**
* **3.375 g dose:** Administer 2.25 g IV every 6 hours.
* **4.5 g dose:** Administer 3.375 g IV every 6 hours.
* **Renal Impairment (CrCl 20-40 mL/min):**
* **3.375 g dose:** Administer 2.25 g IV every 4 hours.
* **4.5 g dose:** Administer 3.375 g IV every 4 hours.
* **Hemodialysis:** Administer the recommended dose, followed by an additional 0.75 g dose after each dialysis session. Dosing frequency should be every 6 hours, not every 8 hours.
## Contraindications
* Known history of severe allergic reaction to piperacillin, other penicillins, beta-lactamase inhibitors, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, liver function test abnormalities.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea (CDAD), neutropenia, thrombocytopenia, seizures (particularly with high doses or renal impairment), interstitial nephritis, hepatitis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. Monitor closely.
* **Warfarin:** May decrease the effect of warfarin, leading to an increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for signs of CDAD (e.g., watery diarrhea, abdominal cramping, fever).
* Periodic assessment of renal and hepatic function, CBC (including platelet count and differential), and electrolytes, especially with prolonged therapy or in patients with risk factors for hematologic or renal toxicity.
## Clinical Pearls
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours if at room temperature.
* Avoid concurrent administration with aminoglycosides in vitro due to potential inactivation of piperacillin; however, they may be administered concomitantly in vivo if indicated.
* Dosing adjustments for renal impairment are crucial.
* The addition of tazobactam broadens the spectrum of activity against many beta-lactamase producing bacteria, including many strains of *Bacteroides* species and *Enterobacteriaceae*.
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*Please verify current prescribing information and institutional protocols before dispensing.*
