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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, and tazobactam, a beta-lactamase inhibitor. It is bactericidal and effective against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and soft tissue infections (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **Higher Dose:** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. The 8-hour interval is typically used for less severe infections or when targeting specific pathogens with lower susceptibility.
* **Maximum Dose:** Dosing is typically capped at 4.5 grams every 6 hours.
## Pediatric Dosing
* **Infants and Children (≥ 2 months):**
* **Total piperacillin dose:** 80-100 mg/kg/day divided every 6 or 8 hours.
* **Tazobactam dose:** 10-12.5 mg/kg/day divided every 6 or 8 hours.
* This typically equates to 100 mg/kg/day of the combined drug (e.g., 9.4 mg/kg of piperacillin and 1.17 mg/kg of tazobactam per dose for an 8-hour interval, or 7 mg/kg piperacillin and 0.875 mg/kg tazobactam per dose for a 6-hour interval).
* **Maximum pediatric dose:** Typically not to exceed the adult dose of 4.5 grams every 6 hours.
* **Neonates (< 2 months):** Dosing in this population is less well-established and should be guided by expert recommendation, considering gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours or 3.375 grams every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours.
* Consider intermittent hemodialysis: Dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known serious allergic reaction (e.g., anaphylaxis) to piperacillin, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, acute kidney injury, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; increased INR monitoring may be necessary.
* **Methotrexate:** May decrease methotrexate clearance, increasing toxicity.
## Monitoring
* Renal function (baseline and periodically)
* Liver function (baseline and periodically)
* Complete blood count (especially for prolonged therapy)
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile*-associated diarrhea
## Clinical Pearls
* The duration of therapy should be based on the severity of infection and clinical response.
* Reconstitute with sterile water or saline and further dilute for infusion. Infusion should be over at least 30 minutes to minimize infusion-related reactions.
* For patients with penicillin allergy, carefully assess the severity of the reaction before considering piperacillin/tazobactam.
* Piperacillin/tazobactam is active against *Pseudomonas aeruginosa*.
* Due to the broad spectrum, use judiciously to avoid resistance development.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for complete and up-to-date details.*
