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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and effective against a broad range of Gram-positive, Gram-negative, and anaerobic bacteria.
### Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin-structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
* Febrile neutropenia (empiric treatment)
* Nosocomial infections caused by piperacillin-resistant *Pseudomonas aeruginosa*
### Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3g/tazobactam 0.375g) every 6 hours intravenously (IV).
* **Severe Infections/Pseudomonas Coverage:** 4.5 grams (piperacillin 4g/tazobactam 0.5g) every 6 or 8 hours IV. Higher doses of 4.5g every 6 hours may be used for more severe infections or those involving *Pseudomonas aeruginosa*.
* **Duration:** Typically 7-10 days, but may be shorter or longer depending on the indication, severity of infection, and clinical response.
### Pediatric Dosing
Dosing is based on piperacillin component.
* **Patients 2 months and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin/kg/dose every 8 hours IV. Maximum dose 4g per dose.
* **Nosocomial pneumonia:** 100 mg piperacillin/kg/dose every 8 hours IV. Maximum dose 4g per dose. For patients with *Pseudomonas aeruginosa*, consider 100 mg piperacillin/kg/dose every 6 hours IV.
* **Neonates and infants younger than 2 months:** Dosing is not well established and should be guided by institutional protocols or expert consultation due to immature renal function.
### Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):**
* 3.375g dose: Give every 8 hours.
* 4.5g dose: Give every 8-12 hours.
* Consider further dose reduction or increased dosing interval for patients on intermittent hemodialysis.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
### Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT), increased serum creatinine.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures (especially at higher doses or with renal impairment).
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** Although often used together, there is potential for antagonism in vitro. Administer separately if co-administered.
### Monitoring
* **Renal function (BUN, creatinine)**
* **Liver function tests (AST, ALT, bilirubin)**
* **Electrolytes**
* **Complete blood count (CBC) with differential**
* **Signs and symptoms of infection**
* **Clostridioides difficile testing if diarrhea develops**
* **INR if patient is on warfarin**
### Clinical Pearls
* Dosing often depends on local institutional protocols, especially for specific indications or severe infections.
* Reconstituted solutions should be infused over at least 30 minutes to minimize infusion-related reactions.
* Higher doses (4.5g) are often preferred for serious infections, including those with *Pseudomonas aeruginosa*, or when dealing with less susceptible organisms.
* Piperacillin/tazobactam does not cover all Gram-negative bacteria, particularly most strains of ESBL-producing organisms or carbapenem-resistant Enterobacteriaceae.
* Be aware of the potential for cross-reactivity in patients with penicillin allergy.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering any medication.
