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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is bactericidal.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin-structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Nosocomial pneumonia (HAP/VAP)
* Empirical treatment of febrile neutropenia
* Anaerobic infections, including those caused by *Bacteroides fragilis*
## Adult Dosing
Standard adult dosing is typically **4.5 g** (piperacillin 4 g / tazobactam 0.5 g) every **6 hours** IV. Doses can be increased to **3.375 g** (piperacillin 3 g / tazobactam 0.375 g) every **4 hours** IV for more severe infections or those caused by less susceptible organisms.
* Complicated intra-abdominal infections: 3.375 g every 6 hours IV.
* Nosocomial pneumonia: 3.375 g every 6 hours IV, or 4.5 g every 6 hours IV for severe cases.
* Febrile neutropenia: 4.5 g every 6 hours IV.
Maximum daily dose for severe infections is generally **18 g** (piperacillin 16 g / tazobactam 2 g) per day.
Duration of therapy is dependent on the indication and clinical response, typically 7-10 days for cIAI and cSSSI, and 7 days for HAP/VAP.
## Pediatric Dosing
Dosing for pediatric patients varies significantly based on age, weight, and indication. Dosing is typically based on the piperacillin component.
* **Children 2 months and older:**
* **Complicated intra-abdominal infections:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
* **Complicated skin and skin-structure infections:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
* **Nosocomial pneumonia:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
* **Febrile neutropenia:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
Tazobactam dose is typically 1/8th of the piperacillin dose. For example, a 100 mg/kg piperacillin dose would correspond to 12.5 mg/kg tazobactam.
**Note:** Specific pediatric dosing protocols should be followed, and dose calculations must account for the piperacillin and tazobactam components.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased dosing interval is required in patients with creatinine clearance (CrCl) < 30 mL/min.
* CrCl 20-30 mL/min: Administer usual dose every 8 hours.
* CrCl 10-20 mL/min: Administer usual dose every 12 hours.
* CrCl < 10 mL/min: Administer usual dose every 12 hours, or 2.25 g every 8 hours.
* Hemodialysis: Administer usual dose every 8 hours and supplement with an additional dose after each dialysis session.
## Contraindications
* Known severe hypersensitivity to piperacillin, other penicillin antibiotics, beta-lactamase inhibitors, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, urticaria, headache, insomnia, eosinophilia, elevated liver enzymes (AST, ALT), thrombocytopenia, leukopenia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), anaphylaxis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, anemia, prolonged bleeding time).
## Key Drug Interactions
* **Probenecid:** Increases piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** Piperacillin may decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While often used concurrently for synergistic activity, consider potential inactivation if mixed directly in the same IV line.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (CBC) with differential and platelet count (baseline and periodically, especially with prolonged therapy or suspected hematologic toxicity).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Clinical signs of infection (fever, white blood cell count, pain, inflammation) for efficacy.
## Clinical Pearls
* Administer IV infusion over at least 30 minutes to reduce the risk of infusion-related reactions.
* Reconstituted solution should be used within 24 hours if stored at room temperature or within 48 hours if refrigerated.
* Dosing for pediatric patients is complex and requires careful calculation based on weight and indication. Always verify pediatric dosing protocols.
* Piperacillin-tazobactam is active against many gram-positive, gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
* Monitor electrolytes, especially sodium, as the drug contains a significant amount of sodium (4.72 mEq per gram of piperacillin).
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**Disclaimer:** This information is intended for clinical pharmacist use and does not replace full prescribing information. Always consult the most current drug monograph, institutional protocols, and patient-specific factors before making therapeutic decisions.
