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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It has broad-spectrum activity against many 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)
* Febrile neutropenia (in combination with an aminoglycoside)
## Adult Dosing
The typical dose is **3.375 grams** (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 6 hours.
Alternatively, **4.5 grams** (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 or 8 hours is also used, depending on institutional protocol and the severity of infection.
Maximum dose is typically **4.5 grams** every 6 hours.
## Pediatric Dosing
Dosing is typically based on the piperacillin component and depends on age and indication.
* **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.
* **Complicated skin and skin-structure infections:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose intravenously every 8 hours.
* **Children 12 to < 18 years:** Dosing is the same as adults (3.375 grams or 4.5 grams IV every 6-8 hours).
Dosing in neonates and infants younger than 2 months is complex and often guided by specialized protocols due to immature renal and hepatic function. The maximum dose for pediatric patients should not exceed the maximum adult dose.
## Dose Adjustments
* **Renal Impairment (CrCl > 20 mL/min):** Extend the dosing interval to every 8 hours for the 3.375g dose or every 8-12 hours for the 4.5g dose.
* **Renal Impairment (CrCl ≤ 20 mL/min):** Administer 2.25 grams (piperacillin 2g/tazobactam 0.25g) intravenously every 6 hours or 3.375 grams (piperacillin 3g/tazobactam 0.375g) intravenously every 8 hours.
* **Hemodialysis:** Administer 2.25 grams (piperacillin 2g/tazobactam 0.25g) intravenously every 8 hours, and administer an additional 0.75 grams (piperacillin 0.5g/tazobactam 0.25g) dose after each dialysis session.
Dosing for pediatric patients with renal impairment should follow specific guidelines.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, leukopenia, neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes.
## 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:** Monitor INR closely as penicillins may decrease warfarin's anticoagulant effect.
* **Methotrexate:** Piperacillin may decrease methotrexate levels; monitor.
## Monitoring
* Renal function (creatinine, BUN)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC)
* Signs and symptoms of infection
* Signs and symptoms of hypersensitivity reactions
* For patients on warfarin, monitor INR.
## Clinical Pearls
* Infusion time should be at least 30 minutes for 3.375g and 4.5g doses to minimize injection site reactions.
* Dosing frequency and duration should be guided by the severity of illness, pathogen susceptibility, and clinical response.
* Adjust dose for renal impairment.
* Consider potential for *C. difficile* infection, especially with prolonged use.
* Tazobactam is a beta-lactamase inhibitor and has minimal intrinsic antibacterial activity.
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*This information is intended for clinical professionals. Always consult the most current prescribing information and institutional protocols for complete details.*
