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# Piperacillin-Tazobactam (Zosyn)
## Overview
A combination formulation containing an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It provides coverage against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
## Primary Indications
* Hospital-acquired and ventilator-associated pneumonia.
* Intra-abdominal infections.
* Skin and skin structure infections.
* Empiric treatment of febrile neutropenia.
* Pelvic inflammatory disease.
## Adult Dosing
The standard dose is **3.375 g IV every 6 hours** (3 g piperacillin/0.375 g tazobactam). For serious infections (e.g., *Pseudomonas*), **4.5 g IV every 6 hours** is recommended. The maximum daily dose is 18 g (piperacillin component).
## Pediatric Dosing
Patients $\geq$ 9 months: **80 mg/kg (piperacillin component) IV every 6 hours**, up to a maximum of 4 g piperacillin per dose (4.5 g total).
*Note: Dosing varies significantly by institutional protocol; verify against local pediatric guidelines.*
## Dose Adjustments
**Renal Impairment:** Requires dose reduction or interval extension based on creatinine clearance (CrCl).
* CrCl 20–40 mL/min: 2.25 g every 6 hours.
* CrCl < 20 mL/min: 2.25 g every 8 hours.
* Hemodialysis: Max 2.25 g every 8 hours, plus a 0.75 g post-dialysis supplement.
## Contraindications
* History of severe hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome) to piperacillin-tazobactam, any other penicillin, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, constipation, headache, insomnia.
* **Serious:** *C. difficile*-associated diarrhea, hypersensitivity reactions (rash, anaphylaxis), neutropenia/thrombocytopenia (usually with prolonged use >10 days), and acute kidney injury (synergistic risk when combined with vancomycin).
## Key Drug Interactions
* **Aminoglycosides:** Inactivation of aminoglycosides if mixed in the same IV line.
* **Methotrexate:** May increase serum levels and toxicity of methotrexate via renal excretion inhibition.
* **Probenecid:** Increases piperacillin half-life and serum levels via inhibition of renal tubular secretion.
* **Warfarin:** Theoretical increased bleeding risk due to alteration of gut flora or anti-platelet effects of certain penicillins.
## Monitoring
* **Renal Function:** Monitor BUN/SCr regularly, especially in patients receiving concomitant nephrotoxins (e.g., vancomycin).
* **Hematology:** CBC with differential weekly for patients on therapy >10 days (risk of leucopenia/neutropenia).
* **Electrolytes:** Contains 2.79 mEq (64 mg) of sodium per 1 gram of piperacillin. Monitor in patients on sodium-restricted diets.
## Clinical Pearls
* **Administration:** Typically administered via extended infusion (over 4 hours) in critically ill patients to maximize the time the free drug concentration remains above the minimum inhibitory concentration (fT>MIC).
* **Stability:** Use IV solutions promptly; refer to manufacturer guidelines for specific compatibility requirements.
* **Spectrum:** Does *not* cover MRSA, VRE, or atypical organisms (*Legionella, Mycoplasma*).
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice varies by institution and patient status. Always verify current prescribing information, institutional antibiograms, and drug-drug interaction databases before initiating therapy.
