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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillinase-resistant penicillin combined 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
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin-Structure Infections, Community-Acquired Pneumonia, Nosocomial Pneumonia:** 3.375 grams (piperacillin 3 g/tazobactam 0.375 g) intravenously every 6 hours.
* **Febrile Neutropenia:** 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 6 hours.
* **Maximum Dose:** Generally 4.5 grams every 6 hours, though higher doses may be used in specific severe infections per institutional guidelines.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and severity of infection. Specific dosing below 12 years of age is often guided by institutional protocols.
* **Children 2 months and older:**
* **Complicated Skin and Skin-Structure Infections:** 100 mg piperacillin/kg/dose every 8 hours and 150 mg piperacillin/kg/day divided every 8 hours.
* **Complicated Intra-abdominal Infections:** 100 mg piperacillin/kg/dose every 8 hours and 150 mg piperacillin/kg/day divided every 8 hours.
* **Febrile Neutropenia, Nosocomial Pneumonia:** 150 mg piperacillin/kg/dose every 6 hours.
* **Maximum Pediatric Dose:** 4.5 grams per dose is generally not to be exceeded.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard doses (3.375g q6h), administer every 8 hours. For higher doses (4.5g q6h), administer every 8-12 hours.
* **Hemodialysis:** Administer dose after dialysis and supplement with an additional dose.
* **Hepatic Impairment:** No dose adjustment is usually necessary.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), Stevens-Johnson syndrome, toxic epidermal necrolysis, neutropenia, thrombocytopenia, prolonged bleeding times.
## Key Drug Interactions
* **Aminoglycosides:** Consider synergistic activity but potential for inactivation of piperacillin at high concentrations. Separate administration times if possible.
* **Probenecid:** Increases and prolongs piperacillin/tazobactam plasma concentrations.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count (CBC) with differential, especially with prolonged therapy.
* Platelet count and coagulation studies if clinically indicated.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile* infection.
## Clinical Pearls
* The reconstituted solution is typically infused over 30 minutes.
* Adjust dose and frequency based on renal function.
* Consider potential for cross-reactivity in patients with penicillin allergy, though the risk is generally considered lower with cephalosporins than with penicillins.
* For empirical treatment of febrile neutropenia, piperacillin/tazobactam is often chosen for its broad spectrum of activity, including against *Pseudomonas aeruginosa*.
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*Please verify current prescribing information with the official drug label or a reliable clinical resource.*
