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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a broad-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including some strains producing beta-lactamases.
## 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)
* Febrile neutropenia (as empiric therapy)
* Bacterial septicemia
## Adult Dosing
* **Standard Dose:** 3.375 g (3 g piperacillin / 0.375 g tazobactam) or 4.5 g (4 g piperacillin / 0.5 g tazobactam) intravenously every 6 or 8 hours.
* **Dosing Frequency:** Typically every 6 hours for most indications. Every 8 hours may be used for less severe infections or with continuous infusion.
* **Maximum Daily Dose:** Generally limited by frequency; some protocols may suggest a maximum of 18 g per day (e.g., 4.5 g every 6 hours).
* **Duration:** Typically 4-14 days, depending on the indication and patient response.
## Pediatric Dosing
Dosing is based on piperacillin component. Consult specific institutional guidelines or pediatric infectious disease resources for precise dosing and indications.
* **Neonates and Infants < 2 months:** Dosing varies significantly by gestational and postnatal age. Consult specialized resources.
* **Children 2 months to 12 years:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Hospital-acquired pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Maximum Pediatric Dose:** Generally 4.5 g per dose.
## Dose Adjustments
* **Renal Impairment:** Dose reduction or increased interval is required.
* CrCl 20-40 mL/min: Reduce dose by 25% or extend interval to every 8 hours (e.g., 3.375 g q8h or 2.25 g q6h).
* CrCl < 20 mL/min: Reduce dose by 50% or extend interval to every 12 hours (e.g., 2.25 g q12h or 3.375 g q12h).
* Hemodialysis: Dose at CrCl < 10 mL/min; administer an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically required, but caution is advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, insomnia, headache, eosinophilia, elevated liver enzymes (ALT, AST).
* **Serious:**
* Hypersensitivity reactions: Anaphylaxis, urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis.
* *Clostridioides difficile*-associated diarrhea (CDAD).
* Seizures (especially with high doses or renal impairment).
* Hepatotoxicity, cholestatic hepatitis.
* Hematologic effects: Neutropenia, thrombocytopenia, leukopenia, anemia, prolonged PT/INR.
* 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:** Piperacillin may decrease the efficacy of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically, especially with prolonged therapy).
* Complete blood count (baseline and periodically, especially with prolonged therapy).
* Signs and symptoms of infection (fever, WBC count, clinical signs).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of CDAD (diarrhea).
* Coagulation parameters (PT/INR) if on warfarin.
## Clinical Pearls
* Piperacillin/tazobactam is a "last resort" antibiotic for many institutions and should be used judiciously to preserve its efficacy.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours when refrigerated.
* When administered intermittently, infuse over at least 30 minutes.
* Continuous infusion may be considered in critically ill patients or those with significant beta-lactamase-producing organisms to maintain higher drug concentrations. Standard doses may be infused over 4 hours. Consult institutional protocols.
* The risk of hypersensitivity reactions is higher in patients with a history of penicillin allergy, but cross-reactivity with cephalosporins is variable.
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*This information is intended for clinical use and does not substitute for professional medical judgment. Always verify current prescribing information with the official product monograph or relevant clinical guidelines.*
