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# Piperacillin-Tazobactam (Zosyn)
## Overview
A combination of a broad-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
Empiric treatment of moderate to severe infections: intra-abdominal infections, nosocomial/ventilator-associated pneumonia, skin and skin structure infections, gynecologic infections, and febrile neutropenia.
## Adult Dosing
Standard dose is 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.
* **Maximum:** 18 g (piperacillin component) per 24 hours.
* **Administration:** Typically infused over 4 hours (extended infusion) in critically ill patients to optimize pharmacodynamics.
## Pediatric Dosing
Dosing varies significantly by institutional protocol; verify with local guidelines.
* **General:** 80–100 mg/kg (piperacillin component) divided every 6 or 8 hours.
* **Neonates (≤ 28 days):** Dosing is complex and dependent on post-menstrual age; neonates are often excluded from standard adult dosing regimens.
## Dose Adjustments
**Renal Impairment:** Requires dose adjustment 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:** Supplementation post-dialysis is typically required (often an additional 0.75 g).
**Hepatic Impairment:** No dosage adjustment necessary.
## Contraindications
History of severe hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome) to any penicillin, cephalosporin, or beta-lactamase inhibitor.
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, injection site reaction.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions, seizures (rare, usually in patients with renal impairment), leukopenia/neutropenia (with prolonged use), and interstitial nephritis.
## Key Drug Interactions
* **Aminoglycosides:** May result in inactivation of the aminoglycoside if mixed in the same IV line. Administer at separate times.
* **Methotrexate:** May increase serum levels and toxicity of methotrexate via inhibition of renal tubular secretion.
* **Warfarin:** May increase INR; monitor closely during therapy.
## Monitoring
* **Renal Function:** Monitor baseline and periodically throughout therapy.
* **CBC:** Monitor for neutropenia or thrombocytopenia if therapy exceeds 10–14 days.
* **Electrolytes:** Monitor for hypokalemia, especially in high-dose/prolonged therapy.
* **Clinical:** Monitor for signs of *C. difficile* infection (e.g., persistent diarrhea).
## Clinical Pearls
* **Pseudomonal Coverage:** Highly effective, but local antibiograms must be reviewed as resistance rates vary by facility.
* **Sodium Load:** Each gram of piperacillin contains approximately 2.8 mEq of sodium; use caution in patients with heart failure or severe sodium restriction.
* **Extended Infusion:** Prolonged IV infusion (over 3–4 hours) is frequently utilized in ICU settings to keep serum concentrations above the minimum inhibitory concentration (MIC) for more of the dosing interval.
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**Educational Disclaimer:** This information is for educational purposes only. Always verify doses, contraindications, and drug interactions against institutional protocols and the most current manufacturer prescribing information before administration.
