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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a penicillinase-susceptible 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
* Febrile neutropenia (empiric treatment)
* Bacterial meningitis (certain etiologies)
## Adult Dosing
Standard adult dose is 3.375 grams (piperacillin 3g/tazobactam 0.375g) every 6 hours or 4.5 grams (piperacillin 4g/tazobactam 0.5g) every 6 or 8 hours, administered intravenously over 30 minutes. Dosing frequency and duration depend on the severity and type of infection. Maximum recommended dose is typically 18 grams per day (piperacillin 16g/tazobactam 2g).
## Pediatric Dosing
For pediatric patients (neonates to 12 years), dosing is based on piperacillin weight and is typically 80-100 mg/kg/day of piperacillin, divided into 3 or 4 doses every 6 or 8 hours. Tazobactam is dosed at a 1:8 ratio to piperacillin (e.g., 10-12.5 mg/kg/day of tazobactam). Consult specific pediatric guidelines for precise dosing and maximums, as this can vary. Dosing for neonates and infants requires careful consideration of renal and hepatic immaturity.
## Dose Adjustments
Dose reduction and/or increased dosing interval is required in patients with renal impairment.
* CrCl 20-50 mL/min: Administer 2.25g every 6 hours or 3.375g every 8 hours.
* CrCl <20 mL/min: Administer 2.25g every 8 hours.
* Hemodialysis: Administer 2.25g every 8 hours and an additional dose after each dialysis session.
Dose adjustments are generally not required for hepatic impairment, but caution is advised.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam use.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and phlebitis at the injection site. Serious adverse effects may include severe hypersensitivity reactions (anaphylaxis), C. difficile-associated diarrhea, seizures (especially with high doses or renal impairment), and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While often used concomitantly, physical incompatibility exists. Separate administration is required.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Electrolytes, BUN, and creatinine.
* Liver function tests.
* Signs and symptoms of infection resolution.
* Signs and symptoms of hypersensitivity reactions.
* Monitor for diarrhea and consider C. difficile testing if symptoms arise.
* INR if co-administered with warfarin.
## Clinical Pearls
* Dose and frequency of administration are critical for efficacy and safety.
* Ensure adequate hydration during administration to minimize phlebitis.
* If administering with other IV drugs, flush the line between administrations.
* Dosing in severe renal impairment and hemodialysis requires careful attention.
* Consider local resistance patterns when initiating therapy.
**Disclaimer:** This information is intended for clinical decision support and does not replace professional medical judgment. Always consult the most current prescribing information and institutional protocols for definitive guidance.
