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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 many bacterial beta-lactamases, extending its spectrum of activity against many beta-lactamase-producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia (as part of combination therapy)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 grams piperacillin / 0.375 grams tazobactam) intravenously every 6 hours.
* **Severe Infections/Higher Inoculum:** 4.5 grams (4 grams piperacillin / 0.5 grams tazobactam) intravenously every 6 or 8 hours.
* **Duration:** Typically 7 to 14 days, depending on the infection and clinical response.
* **Maximum Daily Dose:** Up to 18 grams (16 grams piperacillin / 2 grams tazobactam) per day, usually reserved for severe infections and administered every 4 hours in some institutional protocols.
## Pediatric Dosing
Dosing is based on piperacillin component:
* **Children 2 months and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight intravenously every 8 hours.
* **Severe infections:** May increase to 100 mg piperacillin/12.5 mg tazobactam per kg every 6 hours, or 125 mg piperacillin/15.6 mg tazobactam per kg every 8 hours, not to exceed the adult maximum dose of 4.5 grams per dose.
* **Neonates and Infants < 2 months:** Dosing recommendations are not well established. Consultation with a pediatric infectious disease specialist or a critical care pharmacist is recommended.
## Dose Adjustments
* **Renal Impairment:**
* CrCl 20-50 mL/min: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours. For doses of 3.375 grams, extend interval to 8 hours. For doses of 4.5 grams, extend interval to 12 hours.
* CrCl < 20 mL/min: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours.
* Hemodialysis: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours, with an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment, but monitor liver function.
## Contraindications
* Known history of severe allergic reaction to piperacillin, other penicillin antibiotics, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain, eosinophilia, elevated liver enzymes (AST, ALT).
* **Serious:** Clostridioides difficile-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, leukopenia, prolonged bleeding time).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Live vaccines:** May reduce the efficacy of live vaccines.
## Monitoring
* Renal function (CrCl, BUN, creatinine)
* Liver function (AST, ALT)
* Complete blood count (CBC)
* Electrolytes
* Signs and symptoms of infection and superinfection
* Clostridioides difficile testing if diarrhea develops
* Bleeding time (if clinically indicated)
## Clinical Pearls
* Dosing frequency adjustment in renal impairment is crucial to avoid toxicity.
* Piperacillin/tazobactam is administered via intravenous infusion. Reconstitution and further dilution are required according to manufacturer instructions. Infusion time is typically 30 minutes.
* The risk of seizures is increased with renal impairment and high doses.
* Discontinue if hypersensitivity reaction occurs.
* The choice of dose (3.375g vs. 4.5g) and frequency (q6h vs. q8h) may depend on local institutional protocols and severity of illness.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for definitive treatment decisions.
