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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-type antibiotic and beta-lactamase inhibitor. It is active against a broad spectrum of bacteria, including many Gram-positive, Gram-negative, and anaerobic organisms.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
* Bacterial septicemia
## Adult Dosing
Standard adult dosing is typically 3.375 g (3 g piperacillin / 0.375 g tazobactam) or 4.5 g (4 g piperacillin / 0.5 g tazobactam) IV every 6 or 8 hours.
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia:** 3.375 g or 4.5 g IV every 6 or 8 hours. Duration depends on severity and clinical response.
* **Febrile neutropenia (empiric):** 4.5 g IV every 6 hours.
The specific frequency (every 6 or 8 hours) and duration depend on the indication, severity of infection, and local institutional protocols. The maximum daily dose is typically 18 g (16 g piperacillin / 2 g tazobactam).
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Children 2 months to <12 years:** Dosing varies based on indication and renal function. A common regimen for serious infections is 90 mg piperacillin/11.25 mg tazobactam per kg per dose IV every 8 hours, or 70 mg piperacillin/8.75 mg tazobactam per kg per dose IV every 6 hours. Maximum dose is 4.5 g per dose.
* **Children ≥12 years:** Dose as adults (3.375 g or 4.5 g IV every 6 or 8 hours).
* **Neonates and infants <2 months:** Use is generally not recommended due to limited data and potential for immature renal and hepatic function.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased interval required for CrCl < 40 mL/min.
* CrCl 20-40 mL/min: 2.25 g (2 g piperacillin / 0.25 g tazobactam) or 3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin / 0.25 g tazobactam) or 3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 12 hours.
* For patients on hemodialysis, administer a dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised as drug is cleared renally and hepatically.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of allergic reaction to cephalosporins or carbapenems.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, urticaria, pruritus, headache, insomnia, fever, hypokalemia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, particularly with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, requiring increased monitoring of INR.
* **Methotrexate:** May decrease serum methotrexate concentrations.
* **Tetracyclines, Chloramphenicol:** May antagonize the bactericidal effect of penicillins.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT)
* Electrolytes (especially potassium)
* Complete blood count (CBC), particularly in prolonged therapy or in patients with neutropenia/thrombocytopenia.
* Signs and symptoms of infection.
* Signs of hypersensitivity reactions.
* *Clostridioides difficile* testing if diarrhea occurs.
## Clinical Pearls
* Administer IV infusion over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* Tazobactam extends the spectrum of piperacillin to include many beta-lactamase producing organisms.
* Use cautiously in patients with a history of severe allergy.
* Monitor for signs of superinfection.
* Sodium content is significant (e.g., 3.375 g vial contains ~2.3 mEq sodium).
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**Disclaimer:** This information is intended for clinical pharmacy professionals and is not a substitute for the official prescribing information or a healthcare provider's judgment. Always consult the most current drug monographs and institutional protocols for complete and accurate prescribing details.
