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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and has 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
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously (IV) every 6 hours.
* **Higher Dose:** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) IV every 6 or 8 hours, often used for more severe infections, hospital-acquired pneumonia, or when indicated by susceptibility testing.
* **Infusion:** Typically infused over 30 minutes. Extended infusion (over 4 hours) may be considered for critically ill patients.
## Pediatric Dosing
Dosing varies by indication and patient weight.
* **Children 2 months and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Complicated skin and skin structure infections:** 75 mg piperacillin / 9.375 mg tazobactam per kg per dose IV every 6 hours.
* **Maximum pediatric dose:** Generally not to exceed the adult dose of 4.5 g every 6 or 8 hours.
* **Neonates and infants < 2 months:** Dosing is not well-established due to immature renal and hepatic function. Consult specialized pediatric guidelines or infectious disease consultation.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 50 mL/min: No adjustment needed.
* CrCl 20-50 mL/min: 2.25 g (piperacillin 2 g / tazobactam 0.25 g) IV every 6 hours or 4.5 g (piperacillin 4 g / tazobactam 0.5 g) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g IV every 8 hours.
* **Hemodialysis:** 2.25 g IV every 8 hours, with an additional 0.75 g dose after each dialysis session.
* **Hepatic Impairment:** No specific dosage adjustment recommendations.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, eosinophilia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, liver enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents:** Penicillins can potentiate neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin, requiring closer INR monitoring.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (ALT, AST, bilirubin)
* Complete blood count (CBC) with differential and platelets
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile* infection
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many beta-lactamases, broadening its spectrum of activity.
* Duration of therapy is typically 7 to 14 days, depending on the severity of infection and clinical response.
* Consider de-escalation to a narrower-spectrum agent once culture and susceptibility results are available.
* The 4.5 g dose is preferred for severe infections or when higher drug exposure is desired.
* For pediatric patients, it is crucial to calculate doses based on weight and the specific indication.
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*This information is intended for clinical use and is not a substitute for professional medical advice. Always verify current prescribing information and institutional protocols.*
