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# Piperacillin/Tazobactam (Zosyn)
## Overview
A combination of 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
* Moderate to severe infections including intra-abdominal, skin/skin structure, pneumonia (nosocomial and community-acquired), and gynecologic infections.
* Empiric treatment of febrile neutropenia (often combined with an aminoglycoside).
## Adult Dosing
* **Standard dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* **Severe infections:** 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours.
* **Administration:** Infuse over 4 hours (extended infusion) to improve pharmacodynamic target attainment in critically ill patients, or 30 minutes for standard dosing.
## Pediatric Dosing
Dosing varies significantly by age and indication. Always confirm with local institutional protocol.
* **≥9 months:** 100 mg/kg (piperacillin component) every 8 hours.
* **Febrile Neutropenia:** 80 mg/kg (piperacillin component) every 6 hours.
* **Max dose:** 4.5 g per dose.
## Dose Adjustments
* **Renal Impairment:** Requires dose reduction or interval extension based on creatinine clearance (CrCl).
* CrCl 20–40 mL/min: 2.25 g q6h.
* CrCl <20 mL/min: 2.25 g q8h or 2.25 g q12h depending on clinical severity.
* **Hemodialysis:** Max 2.25 g q8h; administer an additional 0.75 g post-dialysis.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or any component of the penicillin, cephalosporin, or beta-lactamase inhibitor classes (anaphylaxis history).
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (rash, anaphylaxis), neutropenia (with prolonged use), and thrombocytopenia.
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro*; administer at least 1 hour apart.
* **Methotrexate:** May increase serum concentrations of methotrexate, increasing risk of toxicity.
* **Probenecid:** Increases serum half-life of piperacillin/tazobactam by decreasing renal clearance.
* **Warfarin:** Theoretical risk of increased bleeding due to anti-platelet effects of penicillin; monitor INR.
## Monitoring
* **Renal Function:** Monitor BUN/SCr to adjust dosing.
* **Hematologic:** Periodic CBC, especially in patients receiving prolonged therapy (>14 days) due to risk of neutropenia.
* **Electrolytes:** Contains 2.79 mEq (64 mg) of sodium per 1 gram of piperacillin; monitor in patients with fluid/sodium restriction.
## Clinical Pearls
* **Extended Infusion:** Prolonged IV infusion (over 4 hours) is preferred in ICU settings to maximize the time the concentration stays above the MIC (fT>MIC).
* **Drug-Induced AKI:** Emerging data suggests higher rates of acute kidney injury when combined with vancomycin compared to vancomycin paired with other beta-lactams (e.g., cefepime).
* **Spectrum:** Does not cover MRSA or atypical organisms (*Legionella, Mycoplasma, Chlamydia*).
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*Disclaimer: This information is for educational purposes only. Clinical practice guidelines and local drug formularies may vary. Always verify current prescribing information, institutional protocols, and patient-specific dosage requirements via a reliable clinical decision support database (e.g., Lexicomp, UpToDate) before prescribing or administering medication.*
