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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin antibiotic with a 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
* Community-acquired pneumonia
* Hospital-acquired pneumonia, including ventilator-associated pneumonia
* Empirical treatment of febrile neutropenia (in combination with an aminoglycoside or other appropriate agents)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
For severe infections or those caused by less susceptible organisms, doses of 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours may be used.
Maximum daily dose: 18 grams (16g piperacillin/2g tazobactam) IV.
Dosing frequency and duration depend on the indication, severity of infection, and clinical response.
## Pediatric Dosing
* **Patients 2 months and older:**
* Dosing is based on piperacillin component.
* Uncomplicated skin and skin structure infections: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* Complicated intra-abdominal infections, community-acquired pneumonia, hospital-acquired pneumonia, and febrile neutropenia: 300 mg piperacillin/37.5 mg tazobactam per kg per dose IV every 6 hours.
* Maximum dose: 3.375 grams per dose (for every 8-hour dosing) or 4.5 grams per dose (for every 6-hour dosing).
* Maximum daily dose: 18 grams per day.
* **Neonates and infants < 2 months:** Dosing is not established. Use with extreme caution and consult pediatric infectious disease specialists.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* For 3.375g every 6 hours: Administer 2.25 grams every 6 hours.
* For 4.5g every 6 hours: Administer 3.375 grams every 6 hours.
* For 4.5g every 8 hours: Administer 3.375 grams every 8 hours.
* Further adjustments may be needed based on CrCl and dialysis status. Consult specific guidelines or pharmacy.
* **Hepatic Impairment:** No dose adjustment is generally recommended.
## Contraindications
* Known history of severe allergic reaction (e.g., anaphylaxis) to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, constipation, abdominal pain, rash.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with renal impairment and high doses), hematologic effects (neutropenia, thrombocytopenia), hepatotoxicity, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effects of neuromuscular blocking agents.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** Although often used in combination for synergy, co-administration can lead to inactivation of aminoglycosides if mixed in the same IV line. Administer separately.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Complete blood count (may see eosinophilia, transient leukopenia, neutropenia, thrombocytopenia).
* Electrolytes.
* Signs and symptoms of infection and hypersensitivity.
* INR if patient is on warfarin.
## Clinical Pearls
* Dosing is based on the piperacillin component; the ratio is typically 8:1 (piperacillin:tazobactam).
* Infusion-dependent bactericidal activity. Administer IV infusions over at least 30 minutes to reduce the risk of hypersensitivity reactions. Extended infusions (e.g., 4 hours) may be considered for critically ill patients to optimize pharmacokinetic/pharmacodynamic targets, but this may increase the risk of toxicity.
* Discontinue if allergic reaction occurs.
* Consider underlying susceptible pathogens and local resistance patterns when selecting empirical therapy.
* The risk of *C. difficile*-associated diarrhea increases with broad-spectrum antibiotic use.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and your institution's guidelines for the most current and complete drug information. Verify doses and indications before administration.
