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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 beta-lactamase enzymes, thereby extending its spectrum of activity against many beta-lactamase-producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin-structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Nosocomial pneumonia (HAP)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 g (piperacillin 3 g / tazobactam 0.375 g) IV every 6 hours.
* **Higher Dose:** 4.5 g (piperacillin 4 g / tazobactam 0.5 g) IV every 6 or 8 hours. Dosing interval may be extended to every 8 hours in some severe infections or for critically ill patients, often administered as an extended infusion over 4 hours.
* **Maximum Daily Dose:** Generally, 18 g (piperacillin 16 g / tazobactam 2 g) per day, though specific maximums can vary by indication and local protocol.
## Pediatric Dosing
Dosing in pediatric patients varies significantly by age, weight, and indication. Consult specific pediatric guidelines.
* **Children < 2 months:** Dosing is highly individualized and often based on gestational and postnatal age, typically within critical care settings.
* **Children ≥ 2 months:** Dosing is often based on piperacillin weight-based recommendations, with tazobactam given in a 1:8 ratio.
* **cIAI:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose IV every 8 hours.
* **cSSSI:** 75 mg piperacillin / 9.375 mg tazobactam per kg per dose IV every 8 hours.
* **HAP/VAP:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Maximum Pediatric Dose:** Generally limited by the adult maximum of 4.5 g per dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Decrease dose frequency to every 8 hours.
* CrCl < 20 mL/min: Decrease dose frequency to every 12 hours.
* Hemodialysis: Dose after each dialysis session and administer a supplemental dose.
* **Hepatic Impairment:** No specific dose adjustments are typically recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, injection site reactions, headache.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), seizure, neutropenia, thrombocytopenia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin/tazobactam.
* **Aminoglycosides:** Concurrent use may result in physical or chemical inactivation of piperacillin/tazobactam or the aminoglycoside. Avoid coadministration in the same IV line.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Neuromuscular blocking agents:** May prolong the neuromuscular blockade.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests (LFTs) periodically, especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Complete blood count (CBC) for hematologic abnormalities.
## Clinical Pearls
* Piperacillin/tazobactam is often administered as an extended infusion (e.g., 4 hours) for critically ill patients to achieve higher drug concentrations and improve outcomes. This dosing strategy should be guided by local protocols.
* The spectrum includes many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria. It is not active against many atypical pathogens or carbapenem-resistant Enterobacteriaceae.
* Due to the potential for cross-reactivity, caution should be exercised in patients with known penicillin allergies.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for definitive guidance. Clinical decisions should be made based on individual patient factors and clinical judgment.*
