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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. It is a broad-spectrum antibiotic active against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard dose:** 3.375 grams (piperacillin 3g/tazobactam 0.375g) intravenously every 6 hours.
* **Higher dose (for severe infections or suspected resistant pathogens):** 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 6 or 8 hours.
* **Duration of therapy:** Typically 7-10 days, depending on the infection and clinical response. In febrile neutropenia, therapy may be continued for up to 7 days or until neutrophil recovery.
## Pediatric Dosing
Dosing varies significantly by age and indication. Refer to specific pediatric guidelines or institutional protocols. A common regimen for serious infections in children greater than or equal to 2 months is 100 mg piperacillin per kg per dose (with a 12.5 mg tazobactam per kg per dose component) given intravenously every 8 hours. For children weighing over 40 kg, adult dosing may be used.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce the frequency of administration. For 6-hour dosing regimens, administer every 8-12 hours. For 8-hour dosing regimens, administer every 12 hours. Further dose reduction may be warranted based on severity of infection and institutional guidelines.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, and elevated liver enzymes. Serious adverse effects include *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* **Renal function:** Monitor serum creatinine and eGFR, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* **Liver function:** Monitor LFTs, particularly with prolonged therapy.
* **Hematologic parameters:** Monitor CBC, especially with prolonged therapy.
* **Signs of *C. difficile*:** Assess for diarrhea.
* **Signs of hypersensitivity:** Monitor for rash, pruritus, or anaphylactic symptoms.
## Clinical Pearls
* Piperacillin/tazobactam has good activity against *Pseudomonas aeruginosa*.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours if at room temperature.
* Tazobactam extends the spectrum of piperacillin to include many beta-lactamase producing bacteria.
* The maximum recommended daily dose of piperacillin is 24 grams.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols before making clinical decisions.*
