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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many beta-lactamase enzymes, thereby extending its spectrum of activity against beta-lactamase-producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 6 hours.
* **Higher Dose (for severe infections or specific pathogens):** 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 or 8 hours.
* **Maximum Dose:** Dosing is typically based on the piperacillin component, with maximum doses not exceeding 18 grams per day in divided doses.
## Pediatric Dosing
* **Patients 3 months and older:**
* **Intra-abdominal infections:** 100 mg piperacillin / 12.5 mg tazobactam per kg of body weight given intravenously every 8 hours.
* **Hospital-acquired pneumonia:** 100 mg piperacillin / 12.5 mg tazobactam per kg of body weight given intravenously every 8 hours OR 75 mg piperacillin / 9.375 mg tazobactam per kg of body weight given intravenously every 6 hours.
* **Maximum Dose:** Avoid exceeding the adult maximum dose. Dosing in neonates and infants younger than 3 months is not well-established and requires careful consideration.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 50 mL/min: No adjustment needed.
* CrCl 20-50 mL/min: 2.25 grams (piperacillin 2 g / tazobactam 0.25 g) every 6 hours or 3.375 grams every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (piperacillin 2 g / tazobactam 0.25 g) every 8 hours.
* Dose adjustments may also be needed for patients on intermittent hemodialysis.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation.
* **Serious:** Anaphylaxis and other hypersensitivity reactions, Clostridioides difficile-associated diarrhea, seizures (especially at high doses or with renal impairment), liver dysfunction, hematologic changes (e.g., eosinophilia, leukopenia, neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin-tazobactam.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the blockade.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents).
* Liver function tests.
* Complete blood counts.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of Clostridioides difficile infection.
* Prothrombin time/INR if co-administered with warfarin.
## Clinical Pearls
* Administer by slow intravenous infusion over at least 30 minutes.
* The reconstituted solution is stable for a limited time; follow manufacturer instructions for storage and preparation.
* Discontinue if hypersensitivity reaction occurs.
* Consider dose reduction in severe renal impairment.
* Monitor for signs of C. difficile infection, as with broad-spectrum antibiotics.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and current clinical guidelines for the most up-to-date and comprehensive details regarding drug use.
