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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric therapy)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (piperacillin 3g/tazobactam 0.375g) intravenously every 6 hours or 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 8 hours.
* **Severe Infections:** Doses up to 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 4 hours may be used, particularly for severe infections or those caused by less susceptible organisms.
* **Maximum Dose:** Not explicitly defined, but typical regimens do not exceed 4.5 grams every 4 hours.
## Pediatric Dosing
Dosing varies by indication and age. Consult specific pediatric guidelines.
* **Children < 2 years:** Dosing is complex and requires careful calculation based on body surface area or weight and indication.
* **Children ≥ 2 years:**
* **Intra-abdominal infections:** 90 mg/kg (piperacillin component) every 6 hours (using 8:1 ratio formulation). Maximum dose per administration is typically capped at 4.5 grams of piperacillin.
* **Nosocomial pneumonia:** 90 mg/kg (piperacillin component) every 6 hours (using 8:1 ratio formulation). Maximum dose per administration is typically capped at 4.5 grams of piperacillin.
* **Febrile neutropenia:** 90 mg/kg (piperacillin component) every 6 hours (using 8:1 ratio formulation). Maximum dose per administration is typically capped at 4.5 grams of piperacillin.
## Dose Adjustments
* **Renal Impairment (CrCl ≥ 20 mL/min):** No dose adjustment generally needed.
* **Renal Impairment (CrCl < 20 mL/min):**
* For the 3.375 g every 6 hours regimen: 2.25 g every 6 hours.
* For the 4.5 g every 8 hours regimen: 3.375 g every 8 hours.
* For the 4.5 g every 4 hours regimen: 2.25 g every 4 hours.
* **Hemodialysis:** Administer dose after dialysis. Supplemental dose may be needed.
* **Hepatic Impairment:** No dose adjustment necessary.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, fever.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** Increases and prolongs piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially with co-administered nephrotoxic agents or in renal impairment).
* Electrolytes, fluid balance.
* Liver function tests.
* Signs and symptoms of infection.
* Signs and symptoms of hypersensitivity reactions.
* Consider complete blood count (CBC) for prolonged therapy due to risk of neutropenia and thrombocytopenia.
## Clinical Pearls
* Reconstitute and dilute according to manufacturer instructions. Infusion should be over at least 30 minutes. Rapid infusion can increase the risk of adverse effects.
* Gram-negative and anaerobic coverage is broad. Activity against *Pseudomonas aeruginosa* is significant.
* Not typically active against ESBL-producing organisms unless laboratory testing confirms susceptibility.
* Dosing for pediatric patients can be complex and requires careful attention to the specific formulation (e.g., 8:1 vs. 4:1 piperacillin:tazobactam ratio) and indication. Dosing recommendations for pediatrics can vary based on institutional protocols.
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*Please verify current prescribing information with the manufacturer's official product monograph or other reliable resources before making any clinical decisions.*
