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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
Standard doses are typically given as 3.375 g (piperacillin 3 g/tazobactam 0.375 g) or 4.5 g (piperacillin 4 g/tazobactam 0.5 g) every 6 to 8 hours.
* **Complicated Intra-abdominal Infections:** 3.375 g IV every 6 hours or 4.5 g IV every 6 or 8 hours. Duration typically 4-7 days.
* **Complicated Skin and Skin Structure Infections:** 3.375 g IV every 6 hours or 4.5 g IV every 6 or 8 hours. Duration typically 7-14 days.
* **Community-Acquired Pneumonia:** 3.375 g IV every 6 hours.
* **Hospital-Acquired Pneumonia (including VAP):** 3.375 g IV every 6 hours or 4.5 g IV every 6 or 8 hours. Higher doses (4.5 g) or extended infusion (over 4 hours) may be considered for severe infections or pathogens with reduced susceptibility.
## Pediatric Dosing
* **Children 2 months and older:** Dosing is based on piperacillin component.
* **3.375 g vial:** 90 mg piperacillin/11.25 mg tazobactam per kg per dose, administered every 6 hours.
* **4.5 g vial:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose, administered every 6 hours.
* Maximum dose: 4.5 g per dose.
* Duration of therapy varies with indication and severity.
* Dosing in neonates and infants younger than 2 months is not established.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 1/3 to 1/2 and/or increase dosing interval. Specific recommendations vary; consult product information or institutional guidelines.
* **Hepatic Impairment:** No dose adjustment recommended, but monitor closely.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice/hepatic dysfunction associated with prior amoxicillin/clavulanate therapy.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, constipation, abdominal pain, eosinophilia.
* **Serious:** Hypersensitivity reactions (anaphylaxis), C. difficile-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially with co-administered nephrotoxic drugs or in patients with renal impairment).
* Liver function tests.
* Complete blood count (CBC), including platelets.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Administer by intermittent IV infusion over 30 minutes. For higher doses (4.5 g) or in severe infections, consider extended infusion over 4 hours.
* Reconstitute and further dilute according to manufacturer instructions.
* Maximum daily dose for adults is typically 18 g (piperacillin 16 g/tazobactam 2 g).
* Be aware of potential cross-reactivity in patients with penicillin allergy, though it may be less common than with other penicillins.
* The piperacillin to tazobactam ratio is fixed in standard formulations (8:1).
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*Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always verify current prescribing information with the official product monograph or a reliable drug information resource before making clinical decisions.*
