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# Piperacillin/Tazobactam
## Overview
Piperacillin is a broad-spectrum penicillin antibiotic, and tazobactam is a beta-lactamase inhibitor. This combination is active against many gram-positive, gram-negative, and anaerobic bacteria, including some strains that produce beta-lactamases.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Nosocomial urinary tract infections (including pyelonephritis)
* Bacterial meningitis (where resistance is not expected)
* Sepsis
## Adult Dosing
Standard adult dosing is typically 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) or 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 to 8 hours. Duration of therapy is usually 7 to 14 days, depending on the infection severity and pathogen.
Maximum daily dose of piperacillin is typically 18 grams.
## Pediatric Dosing
* **Patients 2 months and older:** Dosing is based on piperacillin component.
* **1 month to < 2 months:** 45 mg/kg (piperacillin component) IV every 8 hours.
* **2 months to < 12 years:** 90 mg/kg (piperacillin component) IV every 8 hours.
* **12 to 18 years:** Same as adult dosing (3.375 g or 4.5 g IV every 6-8 hours).
Maximum dose generally should not exceed 18 g/day (piperacillin component).
* **Neonates (birth to 1 month):** Dosing is often based on weight and gestational age, and exact regimens can vary; consultation with pediatric infectious disease or neonatology is recommended.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer 2.25 g or 3.375 g IV every 8 hours.
* CrCl < 20 mL/min: Administer 2.25 g or 3.375 g IV every 12 hours.
* Consider hemodialysis: Administer 2.25 g or 3.375 g IV every 12 hours and administer an additional dose after each hemodialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, headache, rash, injection site reactions, eosinophilia, leukopenia.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, interstitial nephritis, hepatic dysfunction, hematologic changes (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of neuromuscular blocking agents.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially with CrCl < 40 mL/min).
* Liver function tests.
* Complete blood count (CBC), particularly in prolonged therapy, to monitor for hematologic changes.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Electrolytes.
* Culture and sensitivity results to guide therapy duration.
## Clinical Pearls
* Piperacillin/tazobactam is generally considered safe in pregnancy if clearly needed.
* Reconstitute and dilute according to manufacturer instructions. Infuse over at least 30 minutes to minimize infusion reactions.
* Rapid infusion may increase the risk of seizure activity.
* When co-administered with vancomycin, consider potential for increased risk of nephrotoxicity.
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*This information is intended for clinical pharmacists and prescribers. It is essential to consult the most current prescribing information and institutional protocols for definitive guidance. Dosing and recommendations may vary.*
