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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against a broad range of gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
Treatment of moderate to severe infections including:
* Complicated intra-abdominal infections
* Complicated skin and soft tissue infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3g/tazobactam 0.375g) or 4.5 grams (piperacillin 4g/tazobactam 1g) intravenously every 6 hours.
* **Higher Doses:** Doses up to 4.5 grams every 4 hours may be used for severe infections or infections caused by less susceptible organisms, particularly in critical care settings or for suspected Pseudomonas aeruginosa infections. Dosing may also be based on piperacillin component, up to 4 grams every 4-6 hours. Specific protocols should be consulted.
* **Duration:** Typically 7-14 days, depending on infection severity and clinical response.
## Pediatric Dosing
* **1 month to 12 years:** Dosing is based on the piperacillin component, typically 80-100 mg piperacillin/kg/dose given intravenously every 6 or 8 hours.
* For severe infections or *Pseudomonas aeruginosa*: 100 mg piperacillin/kg/dose every 6 hours.
* Maximum dose: 4 grams of piperacillin per dose (equivalent to 4.5g piperacillin/tazobactam).
* **Neonates and infants < 1 month:** Dosing is more complex and typically based on gestational and postnatal age. Consult specific pediatric guidelines or neonatology services.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer the standard dose every 8 hours.
* CrCl < 20 mL/min: Administer the standard dose every 12 hours.
* For doses administered every 4 hours, the dosing interval should be extended to every 6 hours for CrCl 20-40 mL/min and every 8 hours for CrCl < 20 mL/min. Consider intermittent or continuous infusion for prolonged therapy in renal impairment.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, injection site reactions.
Serious: Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (rare, typically with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Aminoglycosides:** Generally compatible, but can be physically inactivated in the same IV line. Administer separately.
* **Anticoagulants:** Concurrent use may increase bleeding risk.
## Monitoring
* Renal and hepatic function.
* Electrolytes, especially with prolonged therapy or renal impairment.
* Signs and symptoms of infection.
* Signs of hypersensitivity reactions.
* For prolonged therapy: CBC to monitor for hematologic changes (e.g., neutropenia, thrombocytopenia).
* INR if patient is on warfarin.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including *Pseudomonas aeruginosa*.
* Tazobactam broadens the spectrum of piperacillin by inhibiting many beta-lactamases.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Administer IV infusion over at least 30 minutes. For doses > 2g, consider a 45-minute infusion to reduce GI upset.
* Monitor for signs of *C. difficile*-associated diarrhea.
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**Disclaimer:** This information is intended for clinical professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols before administering any medication.
