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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and a beta-lactamase inhibitor. It is active against a broad range of gram-positive, gram-negative, and anaerobic bacteria, including many beta-lactamase-producing strains.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
The typical dose is 3.375 grams (piperacillin 3g/tazobactam 0.375g) or 4.5 grams (piperacillin 4g/tazobactam 0.5g) every 6 or 8 hours.
* **Complicated intra-abdominal infections:** 3.375 g every 6 hours or 4.5 g every 8 hours for 5-14 days.
* **Complicated skin and skin-structure infections:** 3.375 g every 6 hours or 4.5 g every 8 hours for 7-10 days.
* **Community-acquired pneumonia:** 3.375 g every 6 hours for 7 days.
* **Hospital-acquired pneumonia:** 4.5 g every 8 hours for 7-10 days.
Dosing frequency and duration depend on the severity of infection and clinical response.
## Pediatric Dosing
Dosing is based on piperacillin content for patients $\ge$ 2 months of age.
* **Serious infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours.
* **Hospital-acquired pneumonia and severe infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 6 hours.
Maximum single dose should not exceed 4.5 grams.
* **For patients weighing > 40 kg:** Use adult dosing.
* **For patients weighing $\le$ 40 kg:**
* Every 8 hours: 100 mg piperacillin/12.5 mg tazobactam/kg/dose, maximum 3.375 g per dose.
* Every 6 hours: 100 mg piperacillin/12.5 mg tazobactam/kg/dose, maximum 4.5 g per dose.
There is insufficient data for use in neonates and infants < 2 months.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For usual 8-hour dosing regimens, administer every 12 hours. For usual 6-hour dosing regimens, administer every 8 hours. A dose of 2.25g (piperacillin 2g/tazobactam 0.25g) every 8 hours or 3.375g (piperacillin 3g/tazobactam 0.375g) every 12 hours may be considered for severe infections.
* **Renal Impairment (CrCl 20-50 mL/min):** Reduce dose frequency to every 8 hours for regimens typically given every 6 hours, and every 12 hours for regimens typically given every 8 hours.
* **Hemodialysis:** Administer dose after dialysis and every 12 hours thereafter for regimens typically given every 6 hours. For regimens typically given every 8 hours, administer every 12 hours.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam therapy.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, eosinophilia, elevated AST/ALT, hypokalemia.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, hepatic failure.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While often co-administered, concurrent use can lead to inactivation of piperacillin in vitro. However, clinical significance is debated. Physical separation of administration is recommended if co-administered via the same IV line.
## Monitoring
* Renal function (SCr, CrCl)
* Liver function tests (AST, ALT, Bilirubin)
* Complete blood count (CBC) with differential, platelet count
* Electrolytes (especially potassium)
* Signs and symptoms of infection and hypersensitivity reactions
* *Clostridioides difficile* testing if diarrhea develops
## Clinical Pearls
* Piperacillin-tazobactam is administered via IV infusion over at least 30 minutes.
* For severe infections or infections caused by less susceptible organisms, consider increasing the dose or frequency (e.g., 4.5g every 6 hours). This should be guided by local protocols and susceptibility data.
* The extended-infusion (e.g., over 4 hours) or continuous infusion of piperacillin-tazobactam may be beneficial for critically ill patients or those with severe infections or infections due to organisms with reduced susceptibility. Consult institutional guidelines.
* Be aware of the potential for cross-reactivity in patients with penicillin allergies.
* Hypernatremia can occur due to the high sodium content of the reconstituted solution.
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*Please verify current prescribing information for the most up-to-date dosing, indications, contraindications, and safety information.*
