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### Piperacillin/Tazobactam (Zosyn)
#### Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor.
#### Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia (hospital-acquired pneumonia)
* Empirical treatment of febrile neutropenia
* Other serious infections caused by susceptible organisms, including those involving piperacillin-resistant *Pseudomonas aeruginosa*.
#### Adult Dosing
* **Standard Dose:** 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
* **High Dose (e.g., for severe *Pseudomonas aeruginosa* infections, hospital-acquired pneumonia, febrile neutropenia):** 4.5 grams IV every 6 hours.
* **Maximum Dose:** Not explicitly defined, but doses above 4.5 grams every 6 hours are typically reserved for specific, severe infections and may not offer additional benefit.
#### Pediatric Dosing
Dosing varies significantly by indication and patient weight. Dosing is often based on the piperacillin component.
* **General Dosing:**
* **3 months to 12 years:** 90-100 mg piperacillin/kg/dose IV every 6-8 hours (not to exceed 4.5 grams per dose). Maximum dose should not exceed adult maximums.
* **Specific Indications (e.g., febrile neutropenia):** May require higher doses, such as 100 mg piperacillin/kg/dose IV every 6 hours (not to exceed 4.5 grams per dose).
* **Neonates:** Dosing in neonates is complex and requires careful consideration of gestational and postnatal age. Consult specific pediatric guidelines or pharmacy for precise recommendations.
#### Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer the usual dose every 8 hours.
* CrCl < 20 mL/min: Administer the usual dose every 12 hours.
* **Hemodialysis:** Administer usual dose every 12 hours. An additional dose (3.375 g) should be given after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
#### Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
#### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, abdominal pain.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), hematologic effects (neutropenia, thrombocytopenia, anemia), hepatotoxicity, interstitial nephritis.
#### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While often used concomitantly for broader coverage, there is a potential for antagonism if mixed in the same IV line; separate administration.
#### Monitoring
* **Renal function:** Monitor serum creatinine and electrolytes, especially in patients with renal impairment or those receiving nephrotoxic agents.
* **Liver function:** Monitor ALT, AST, bilirubin, especially with prolonged therapy.
* **Hematologic parameters:** Monitor CBC with differential and platelets, particularly with prolonged therapy or in patients with neutropenia.
* **Signs of infection:** Monitor for clinical improvement (fever, WBC count, symptoms).
* **Signs of CDAD:** Monitor for diarrhea, abdominal cramping, and fever.
* **Hypersensitivity reactions:** Educate patients and monitor for rash, urticaria, dyspnea.
#### Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against *Pseudomonas aeruginosa* and many Gram-positive and anaerobic bacteria.
* Tazobactam extends the spectrum of activity by inhibiting many beta-lactamases.
* The 3.375 g formulation contains 3 g piperacillin and 0.375 g tazobactam. The 4.5 g formulation contains 4 g piperacillin and 0.5 g tazobactam.
* For patients requiring intermittent infusions, reconstitute and further dilute to a concentration no greater than 45 mg piperacillin per mL (e.g., 3.375 g in 75 mL, 4.5 g in 100 mL) and infuse over 30 minutes.
* Continuous infusion may be considered for severe infections or to achieve higher drug concentrations, particularly for *Pseudomonas aeruginosa*. Consult local protocols for continuous infusion dosing.
* Do not add piperacillin/tazobactam to lipid emulsions or other non-IV fluid solutions.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours when refrigerated. Infuse solutions at room temperature.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and current clinical guidelines for the most up-to-date and comprehensive drug information before making any clinical decisions.
