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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial agent and a beta-lactamase inhibitor. It is active against a broad spectrum of gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
Standard dose: 3.375 grams every 6 hours intravenously.
Alternative for more severe infections or *Pseudomonas aeruginosa* infections: 4.5 grams every 6 hours intravenously.
Maximum dose: Generally not to exceed 18 grams per day, depending on indication and severity. Duration of therapy is typically 7 to 14 days.
## Pediatric Dosing
* **Infants and Children (up to 12 years):** Dosing is based on piperacillin component, typically 100 mg/kg/dose (piperacillin equivalent) administered intravenously every 6 to 8 hours. Maximum dose of 4 grams per dose. **Note:** Dosing for neonates and infants < 12 months is complex and requires careful consideration of gestational and chronological age, renal function, and specific indication. Consult specialized pediatric infectious disease resources.
* **Adolescents (12 years and older):** Can be dosed as adults.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 50 mL/min: No adjustment needed.
* CrCl 20-50 mL/min: 2.25 grams every 6 hours (standard dose) or 3.375 grams every 6 hours (higher dose).
* CrCl < 20 mL/min: 2.25 grams every 8 hours (standard dose) or 3.375 grams every 8 hours (higher dose).
* Hemodialysis: Administer the dose above for CrCl < 20 mL/min, and administer an additional 0.75 g dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of a severe allergic reaction (e.g., anaphylaxis) to any beta-lactam antibiotic.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## 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.
* **Aminoglycosides:** Concurrent use can lead to physical inactivation of piperacillin if mixed in the same IV line. Administer separately.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT)
* Complete blood count (CBC) with differential, especially if prolonged therapy
* Signs and symptoms of infection
* Electrolytes, especially in renal impairment
* INR if patient is on warfarin
## Clinical Pearls
* Piperacillin/tazobactam provides broad-spectrum coverage, including *Pseudomonas aeruginosa*, but resistance is increasing. Susceptibility testing is crucial.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated. Infuse over at least 30 minutes.
* Be aware of the potential for cross-reactivity in patients with penicillin allergies, although it is less common with extended-spectrum penicillins.
* The risk of *C. difficile*-associated diarrhea is a concern with all broad-spectrum antibiotics.
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*Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always verify current prescribing information and consult relevant guidelines before making treatment decisions.*
