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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Nosocomial infections caused by piperacillin-resistant, beta-lactamase producing Gram-negative pathogens, in conjunction with an aminoglycoside or fluoroquinolone if needed.
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **High-Dose (for more severe infections or institutions with higher resistance):** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. The 8-hour dosing is less common and often reserved for specific indications or once step-down therapy is initiated. The 6-hour interval is generally preferred for critically ill patients or those with severe infections.
* **Maximum Recommended Dose:** Typically 4.5 grams every 6 hours.
## Pediatric Dosing
Dosing in pediatric patients varies significantly by age and indication. Always consult specific pediatric guidelines.
* **Patients 0 to <1 year:** Typically dosed based on piperacillin component ranging from 50 mg/kg to 100 mg/kg every 6 to 8 hours.
* **Patients 1 to <2 years:** Dosing based on piperacillin component ranging from 75 mg/kg to 100 mg/kg every 6 to 8 hours.
* **Patients 2 to <12 years:** Dosing based on piperacillin component typically 75 mg/kg to 100 mg/kg every 6 to 8 hours.
* **Patients ≥12 years:** Dosed as adults.
* **Maximum pediatric dose:** Generally does not exceed adult maximums. For pediatric patients weighing <40 kg, dose should not exceed the adult dose of 4.5 g every 6 hours.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Dosing frequency and/or dose reduction is required. Specific recommendations vary, but generally for CrCl < 20 mL/min, doses are reduced by 25-50% and administered every 8 hours instead of 6 hours. Consult pharmacy for specific recommendations based on CrCl. Hemodialysis may require supplemental dosing.
## Contraindications
* Known serious allergy to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, fever, abdominal pain, elevated liver enzymes (AST, ALT).
* **Serious:** Anaphylaxis, hypersensitivity reactions, Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic abnormalities (neutropenia, leukopenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents:** Piperacillin may prolong the action of rocuronium and vecuronium.
* **Warfarin:** Monitor INR closely; case reports suggest potential for reduced efficacy.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Tetracyclines:** May antagonize the action of penicillins.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** Baseline and periodically, especially with prolonged therapy.
* **Signs and symptoms of hypersensitivity reactions.**
* **Signs and symptoms of CDAD.**
* **Therapeutic drug monitoring (TDM) for piperacillin is not routinely recommended, but may be considered in specific situations (e.g., critically ill patients, suspected resistance).**
## Clinical Pearls
* The 3.375 g and 4.5 g vials are reconstituted and further diluted for IV infusion. Total infusion time should be at least 30 minutes.
* Ensure adequate hydration to minimize the risk of crystalluria.
* Consider the spectrum of activity for appropriate empiric use and for targeted therapy. Piperacillin/tazobactam has good activity against Pseudomonas aeruginosa.
* Tazobactam inhibits many beta-lactamases but not all. Resistance can emerge.
* Risk of cross-reactivity with other beta-lactam antibiotics.
**Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. Always refer to the most current prescribing information, institutional protocols, and drug references for complete details and to ensure patient safety.
