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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active 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
* Febrile neutropenia (in combination with an aminoglycoside)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **High Dose (for severe infections or hospital-acquired pneumonia):** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
* **Duration:** Typically 7-14 days, depending on the indication and clinical response.
## Pediatric Dosing
* **Children 0 to < 2 months:** Dosing is highly variable and depends on weight, gestational age, and severity of infection. Consult specific pediatric guidelines.
* **Children 2 months to 12 years:**
* **Weight-based:** 90 to 100 mg piperacillin/kg/day administered intravenously in equally divided doses every 6 or 8 hours.
* **Maximum:** The total daily dose should not exceed the adult maximum of 13.5 grams.
* **Maximum per dose:** The piperacillin component should not exceed 4 grams per dose.
* **Children > 12 years:** Same as adult dosing.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 33% to 50% and increase dosing interval to every 8 hours. If using 4.5g every 8 hours, may need further reduction.
* **Renal Impairment (CrCl 20-50 mL/min):** May require dose reduction and/or increased dosing interval. Consult specific guidelines.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of immediate or severe allergic reaction to these agents.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Fever, eosinophilia
* Thrombocytopenia, leukopenia
* Elevated liver enzymes
* *Clostridioides difficile*-associated diarrhea
* Hypersensitivity reactions, including anaphylaxis
## 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:** Monitor INR closely; potential for increased anticoagulant effect.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* **Renal function:** Especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** Monitor for hematologic changes.
* **Electrolytes:** Monitor for imbalances, particularly with prolonged therapy.
* **Signs and symptoms of infection:** Clinical response to therapy.
* **INR:** If co-administered with warfarin.
* **Methotrexate levels:** If co-administered with methotrexate.
## Clinical Pearls
* The reconstituted solution must be infused over at least 30 minutes.
* Piperacillin/tazobactam has broad-spectrum activity, including *Pseudomonas aeruginosa*.
* Tazobactam inhibits many beta-lactamases, extending the spectrum of piperacillin.
* The dose is expressed as the total piperacillin/tazobactam content (e.g., 3.375g or 4.5g).
* For suspected *C. difficile* infection, piperacillin/tazobactam should be discontinued.
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**Disclaimer:** This information is intended for clinical professionals. Always verify current prescribing information, local protocols, and patient-specific factors before initiating therapy.
