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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam).
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
## Adult Dosing
The standard dose is 3.375 g (3g piperacillin/0.375g tazobactam) or 4.5 g (4g piperacillin/0.5g tazobactam) IV every 6 hours. Higher doses, such as 4.5 g every 4 hours, may be used for severe infections or in critically ill patients, particularly those with suspected or documented resistant pathogens. Dosing frequency and duration should be guided by the severity of illness, pathogen susceptibility, and clinical response.
## Pediatric Dosing
Dosing in pediatric patients is based on piperacillin weight:
* **Neonates and infants (0-3 months):** Generally 80 mg piperacillin/10 mg tazobactam per kg per dose IV every 8 hours. Specific dosing for this age group should be guided by institutional protocols and expert consultation due to immature renal function.
* **Children (3 months and older):** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours or 80 mg piperacillin/10 mg tazobactam per kg per dose IV every 8 hours. Maximum dose of 4.5 g every 6 or 8 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment.
* CrCl 20-40 mL/min: 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) IV every 12 hours.
* Hemodialysis: 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) IV every 8 hours, with an additional dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain.
Serious: Anaphylaxis, Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), hematologic abnormalities (neutropenia, thrombocytopenia, eosinophilia), interstitial nephritis, hepatitis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Aminoglycosides:** In vitro data suggests potential inactivation of piperacillin by aminoglycosides. However, coadministration is often clinically necessary and may be synergistic; administer separately if possible.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the efficacy of warfarin; increased INR monitoring is recommended.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (periodically).
* Complete blood count (periodically, especially with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Consider the piperacillin-to-tazobactam ratio when prescribing; 3.375 g and 4.5 g formulations are commonly used.
* Reconstituted solutions should be used within 24 hours at room temperature or within 48 hours if refrigerated.
* Infusion rate is important to minimize infusion-related reactions. Infuse over at least 30 minutes. For 4.5 g doses, a 45-minute infusion is recommended.
* Adjust therapy based on culture and sensitivity results when available.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for complete details and to verify drug information before use.
