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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 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)
* Febrile neutropenia (in combination with an aminoglycoside or other appropriate agent)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
High dose: 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
Maximum daily dose: Typically 18 grams (16g piperacillin/2g tazobactam) per day for severe infections, although specific indications and patient factors may influence this.
Duration of therapy is typically 7-14 days.
## Pediatric Dosing
* **Patients ≥ 12 years of age:** Same as adult dosing.
* **Patients < 12 years of age:**
* **2 months to < 12 years:** 90 mg piperacillin component per kg per dose (e.g., 75 mg piperacillin/9.375 mg tazobactam per kg per dose) intravenously every 6 hours or 112.5 mg piperacillin component per kg per dose (e.g., 100 mg piperacillin/12.5 mg tazobactam per kg per dose) intravenously every 8 hours.
* **Note:** Maximum single dose should not exceed the adult dose of 4.5 grams. For patients with cystic fibrosis, doses up to 150 mg piperacillin component per kg per dose every 6 hours have been used, but this is off-label and requires specialist guidance.
* **Neonates and infants < 2 months:** Dosing recommendations are not well established due to immature renal and hepatic function. Consult pediatric infectious disease specialists.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: Reduce dose by 25% or increase interval to every 8 hours.
* CrCl < 20 mL/min: Reduce dose by 50% or increase interval to every 8 or 12 hours.
* For intermittent hemodialysis: Give dose every 12 hours and administer an additional dose (e.g., 2.25g or 3.375g) after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactam inhibitors.
* History of cholestatic jaundice/hepatic dysfunction associated with prior piperacillin-tazobactam therapy.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain.
Serious: Hypersensitivity reactions (anaphylaxis), C. difficile-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** May decrease the anticoagulant effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Aminoglycosides:** In vitro data suggest potential inactivation of aminoglycosides by piperacillin. While often co-administered, consider separate administration lines if possible.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function (ALT, AST, bilirubin)
* Complete blood count (CBC) with differential and platelet count
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of C. difficile infection
* Clinical signs of infection resolution
## Clinical Pearls
* Piperacillin/tazobactam is a common empiric choice for serious bacterial infections, particularly those involving resistant organisms like *Pseudomonas aeruginosa*.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Administration is typically over 30 minutes (intermittent infusion) or via continuous infusion for higher doses and potentially improved efficacy/reduced toxicity. Specific protocols for continuous infusion vary.
* Be aware of potential for cross-reactivity in patients with penicillin allergies, though rates are lower than with earlier penicillins.
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**Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.
