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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and 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
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours IV.
* **Higher Dose (e.g., severe infections, nosocomial pneumonia, febrile neutropenia):** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV.
* **Dosing may be guided by local protocols or institutional guidelines, particularly for severe infections.**
## Pediatric Dosing
* **Children 2 to 12 years:** 93.75 mg/kg (80mg piperacillin/10mg tazobactam) every 6 hours IV.
* **Maximum dose per administration:** 3.375 grams.
* **For febrile neutropenia:** 112.5 mg/kg (90mg piperacillin/22.5mg tazobactam) every 6 hours IV.
* **Maximum dose per administration:** 4.5 grams.
* **For neonates and infants < 2 months:** Dosing is highly variable and depends on gestational and postnatal age. Consult specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Dose reduction or increased dosing interval is typically required. Consult specific guidelines for precise adjustments.
* **For standard 3.375g q6h:** Administer 2.25g every 6-8 hours, or 3.375g every 8 hours.
* **For higher 4.5g q6h:** Administer 3.375g every 6-8 hours, or 4.5g every 8 hours.
* **Hepatic Impairment:** No dose adjustment generally recommended.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, leukopenia, eosinophilia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, anaphylaxis, hypersensitivity reactions, seizures (rare, particularly with high doses or renal impairment), interstitial nephritis, hemolytic anemia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the effect of warfarin, increasing INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate serum levels; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and during therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* Complete blood counts, especially with prolonged therapy or suspected hematologic toxicity.
* Liver function tests may be considered.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often used in serious infections, including those caused by resistant organisms.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated. Infuse over 30 minutes.
* The risk of seizure is increased in patients with renal impairment and those receiving high doses.
* Consider discontinuing and switching to an agent with a narrower spectrum once culture and sensitivity results are available.
**Please verify current prescribing information and institutional protocols before initiating therapy.**
