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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. It has broad-spectrum activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Community-acquired pneumonia
* Febrile neutropenia (empiric treatment)
* Bacterial meningitis (when indicated by susceptibility)
## Adult Dosing
Standard dose: 3.375 g (piperacillin 3 g / tazobactam 0.375 g) or 4.5 g (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 or 8 hours. Dosing frequency and duration depend on the indication, severity of infection, and patient response. Dosing is often weight-based for specific indications like febrile neutropenia or when significant fluid overload is present. Higher doses (e.g., 4.5 g IV every 4 hours) may be used for severe infections or organisms with reduced susceptibility.
## Pediatric Dosing
Dosing in pediatric patients is highly variable and depends on age, weight, and indication. Refer to specific institutional guidelines or pediatric infectious disease resources.
* **Neonates (<1 week):** Generally 60-80 mg piperacillin/kg/dose IV every 12 hours.
* **Neonates (1-4 weeks):** Generally 80-100 mg piperacillin/kg/dose IV every 8 hours.
* **Children (>1 month):** Generally 90-100 mg piperacillin/kg/dose IV every 6-8 hours.
**Note:** These are general guidelines; precise dosing requires careful calculation based on total daily dose and interval. Maximum doses should not be exceeded.
## Dose Adjustments
**Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose by 25% or increase dosing interval by 2 hours (e.g., every 8 hours instead of 6 hours).
* CrCl < 20 mL/min: Reduce dose by 50% or increase dosing interval by 4 hours (e.g., every 12 hours instead of 6 hours).
* Hemodialysis: Administer dose at the end of hemodialysis. Give 2.25 g (piperacillin 2 g / tazobactam 0.25 g) or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) IV every 8 hours. Supplemental doses (e.g., 0.75 g or 1.125 g) may be needed after each dialysis session.
**Hepatic Impairment:** No dose adjustment recommended.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam therapy.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia.
Serious: *Clostridioides difficile*-associated diarrhea, anaphylaxis, hypersensitivity reactions, seizures (especially with high doses or renal impairment), Stevens-Johnson syndrome/toxic epidermal necrolysis, hepatic dysfunction, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** Increases piperacillin/tazobactam serum concentrations.
* **Aminoglycosides:** In vitro antagonism with some Gram-negative organisms; consider separate administration. In vivo, synergistic activity is possible.
* **Warfarin:** May decrease the effectiveness of warfarin. Monitor INR closely.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels and consider dose adjustments.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Complete blood count (CBC) for hematologic changes (neutropenia, thrombocytopenia) with prolonged therapy.
* Liver function tests (LFTs) periodically, especially in patients with pre-existing hepatic impairment or receiving prolonged therapy.
* Clinical signs of infection for efficacy.
* Electrolytes, especially with large fluid volumes.
## Clinical Pearls
* Administer by slow intravenous infusion over at least 30 minutes.
* Reconstituted solution stability varies; follow manufacturer instructions.
* May be used in combination with an aminoglycoside for synergistic coverage of difficult-to-treat Gram-negative organisms, particularly *Pseudomonas aeruginosa*.
* Dose adjustments for renal impairment are crucial.
* Discontinue if hypersensitivity reaction or *C. difficile*-associated diarrhea occurs.
* Consult institutional antibiogram for local resistance patterns.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details and to ensure patient safety. Dosing and management may vary based on individual patient factors and local protocols.
