Please check your internet connection and try again.
# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It provides broad-spectrum coverage against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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 (often in combination regimens)
## Adult Dosing
* **Standard Dosing:** 3.375 g or 4.5 g IV every 6 or 8 hours. The 4.5 g dose provides higher piperacillin exposure and is often preferred for more serious infections or organisms requiring higher concentrations (e.g., *Pseudomonas aeruginosa*).
* **Duration:** Varies by indication and patient response, typically 4-14 days.
* **Maximum Dose:** Not explicitly defined, but higher doses are typically based on clinical judgment and specific indications.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and severity of infection. Consult institutional guidelines or specific pediatric resources for precise dosing. Common regimens include:
* **Neonates and Infants:** 100 mg piperacillin/12.5 mg tazobactam/kg/day divided into doses every 8 or 12 hours.
* **Children > 6 months:** 200 mg piperacillin/25 mg tazobactam/kg/day divided into doses every 6 or 8 hours.
* **Maximum Dose:** Typically limited to adult maximums (e.g., 4.5 g per dose).
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 g or 3.375 g IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g or 3.375 g IV every 12 hours.
* Hemodialysis: Administer dose after hemodialysis. Dose adjusted as above for CrCl < 20 mL/min, and an additional dose is recommended after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, rash.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of piperacillin and tazobactam.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While often used together, there is a potential for physical or chemical inactivation if mixed. Administer separately.
## Monitoring
* **Renal function:** Baseline and periodic monitoring, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* **Liver function:** Baseline and periodic monitoring, especially with prolonged therapy or pre-existing liver disease.
* **Hematologic parameters:** Complete blood count (CBC) may be monitored for signs of hematologic toxicity (neutropenia, thrombocytopenia).
* **Signs and symptoms of infection:** Clinical response to therapy.
* **Signs and symptoms of hypersensitivity reactions.**
* **Stool for *C. difficile*:** If diarrhea develops during or after treatment.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often used empirically for serious bacterial infections.
* Reconstituted solutions should be infused over at least 30 minutes to minimize infusion-related reactions.
* The risk of seizures may be increased in patients with renal impairment or those receiving high doses.
* Discontinuation may be necessary if hypersensitivity reactions occur.
* Consult local antibiograms for resistance patterns and guidance on appropriate use.
***
**Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive patient management. Dosing and recommendations may vary based on patient-specific factors and evolving clinical guidelines.
