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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and a beta-lactamase inhibitor. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Nosocomial pneumonia
* Community-acquired pneumonia
* Bacterial meningitis (where resistance is not suspected)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
The typical dose is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours. Duration of therapy is typically 7-14 days depending on the indication and clinical response. Dosing frequency and duration may be guided by local protocols and patient-specific factors.
## Pediatric Dosing
* **Children 2 months and older:** Dosing is based on piperacillin component.
* **3.0 g/kg/day of piperacillin**, administered every 6 or 8 hours. Maximum daily dose of piperacillin is 12 g/day.
* **2 months to < 12 years or < 40 kg:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours.
* **12 years or older and ≥ 40 kg:** Use adult dosing.
Dosing for neonates and infants < 2 months is not well established and requires careful consideration and consultation.
## Dose Adjustments
**Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: Administer 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) every 8 hours.
* CrCl < 20 mL/min: Administer 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) every 12 hours.
Dose reduction and/or increased dosing interval may be necessary based on local protocol and patient response.
**Hepatic Impairment:** No dose adjustment is generally recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin-tazobactam use.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, phlebitis/thrombophlebitis.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the effect of warfarin; increased INR monitoring is recommended.
* **Methotrexate:** Piperacillin may decrease methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (periodically).
* Complete blood count (especially in prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
## Clinical Pearls
* Administer IV infusion over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* Avoid rapid IV push.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours if refrigerated.
* Adjust dosing for renal impairment.
* Tazobactam inhibits beta-lactamases, extending the spectrum of piperacillin to include many resistant organisms.
* Empirical use in febrile neutropenia is common, but local resistance patterns should be considered.
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*Disclaimer: This information is intended for clinical pharmacists and is not a substitute for professional medical advice. Always verify current prescribing information, guidelines, and patient-specific factors before making therapeutic decisions.*
