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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of a broad-spectrum penicillinase-susceptible penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and inhibits bacterial cell wall synthesis.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Nosocomial urinary tract infections
* Moderate to severe infections caused by piperacillin-susceptible, beta-lactamase-producing Gram-negative and Gram-positive bacteria.
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 6 hours intravenously (IV).
* **Higher Dose:** 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) every 6 or 8 hours IV.
* **Maximum Dose:** Not explicitly defined for typical indications, but higher doses are used for severe infections. Dosing is often guided by local protocols and institutional guidelines.
## Pediatric Dosing
* **3 months and older:**
* **Intra-abdominal Infections:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose every 8 hours IV.
* **Complicated Skin and Skin Structure Infections:** 75 mg piperacillin / 9.375 mg tazobactam per kg per dose every 6 hours IV.
* **Maximum Dose:** Generally not to exceed the maximum adult dose of 4.5 grams every 6 hours. Dosing for children weighing over 40 kg should be the same as the adult dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl 20-40 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours OR 3.375 grams every 8 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours.
* Consider intermittent hemodialysis: Dose administered after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, dyspnea.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic dysfunction, interstitial nephritis, neutropenia, thrombocytopenia, prolonged bleeding times.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular Blocking Agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Bacteriostatic Antibiotics:** May antagonize the bactericidal effect of piperacillin-tazobactam.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for *C. difficile*-associated diarrhea.
* Monitor renal and hepatic function, complete blood counts (especially in prolonged therapy), and coagulation parameters.
## Clinical Pearls
* Tazobactam broadens the spectrum of piperacillin by inhibiting many beta-lactamases.
* Administer by slow IV infusion over at least 30 minutes.
* Ensure adequate hydration and electrolytes, especially in patients receiving diuretics or those with renal impairment.
* The choice of dose and duration should be guided by the severity and site of infection and by the suspected or identified pathogens.
* Do not mix with dextrose solutions.
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*This information is intended for healthcare professionals. Please consult the most current prescribing information and local institutional guidelines for complete details, including indications, contraindications, warnings, precautions, adverse reactions, and drug interactions, as recommendations can vary.*
