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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active 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)
* Empirical treatment of febrile neutropenia
### Adult Dosing
* **Standard Dosing:** 3.375 grams (3 g piperacillin / 0.375 g tazobactam) intravenously every 6 hours.
* **Higher Dosing (for severe infections or documented resistant organisms):** 4.5 grams (4 g piperacillin / 0.5 g tazobactam) intravenously every 6 or 8 hours. Dosing frequency may be extended to every 4 hours for critically ill patients with renal dysfunction or specific indications, based on institutional protocols.
* **Maximum Daily Dose:** Generally not to exceed 18 grams per day (based on 4.5 g every 6 hours).
### Pediatric Dosing
* **For patients 2 months and older:** Dosing is based on piperacillin component.
* **2 months to <12 years:** 100 mg/kg/day of piperacillin, administered as 25 mg/kg every 6 hours. This corresponds to a total piperacillin/tazobactam dose of 112.5 mg/kg/dose (90 mg piperacillin/11.25 mg tazobactam per kg per dose).
* **12 years and older:** Dosing is the same as adult dosing.
* **Neonates and infants <2 months:** Dosing is not well established and should be guided by institutional protocols or specialist consultation, considering gestational and postnatal age.
### Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: 2.25 grams (2 g piperacillin / 0.25 g tazobactam) every 6 hours.
* CrCl < 20 mL/min: 2.25 grams (2 g piperacillin / 0.25 g tazobactam) every 8 hours.
* For higher doses (4.5 g), adjust accordingly (e.g., 4.5 g every 8 hours for CrCl 20-39 mL/min, 4.5 g every 12 hours for CrCl < 20 mL/min).
* **Hemodialysis:** Administer dose after hemodialysis session. Dose for CrCl < 20 mL/min should be used, and an additional dose (2.25 g or 4.5 g depending on the regimen) should be given during hemodialysis.
### Contraindications
* Known history of hypersensitivity to piperacillin, other penicillin antibiotics, tazobactam, or any other component of the formulation.
* History of immediate and severe allergic reaction to a beta-lactam antibiotic.
### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, constipation, abdominal pain, elevated liver enzymes (AST, ALT).
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, acute kidney injury.
### Key Drug Interactions
* **Aminoglycosides:** Potential for synergistic activity, but also increased risk of nephrotoxicity. Concurrent use requires careful monitoring of renal function.
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin, leading to an increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
### Monitoring
* Renal function (serum creatinine, BUN)
* Liver function tests (AST, ALT)
* Complete blood count (CBC) with differential and platelet count
* Signs and symptoms of infection and clinical response
* Electrolytes, especially with prolonged therapy or in specific patient populations.
* INR if patient is on warfarin.
### Clinical Pearls
* Piperacillin/tazobactam is administered via intravenous infusion. Reconstitute and dilute according to manufacturer instructions. Infusion time is typically 30 minutes for standard doses, but longer infusions (e.g., 4 hours) may be used for higher doses or in critically ill patients to achieve higher drug concentrations.
* When reconstituting powders, be aware of the sodium content, particularly in patients requiring sodium restriction.
* Consider empiric dose adjustments for renal impairment.
* Tazobactam inhibits beta-lactamases, extending the spectrum of activity against many beta-lactamase-producing organisms.
* For penicillin-allergic patients, consider the potential for cross-reactivity, especially in those with a history of severe immediate reactions to other penicillins or cephalosporins.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult current prescribing information and institutional guidelines for definitive dosing and management.
