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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal and active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) IV every 6 hours.
* **High Dose:** 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) IV every 6 or 8 hours. Higher doses are often used for more severe infections, infections with resistant organisms (e.g., *Pseudomonas aeruginosa*), or in critically ill patients. Specific indication-based dosing protocols may exist locally.
* **Duration of Therapy:** Typically 4-14 days, depending on the indication and clinical response.
## Pediatric Dosing
* **Infants and Children (≥ 2 months):** Dosing is based on the piperacillin component.
* **General Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Serious Infections (e.g., *Pseudomonas aeruginosa*):** 150 mg piperacillin/18.75 mg tazobactam per kg per dose IV every 6 hours.
* **Maximum Dose:** For children, avoid exceeding the adult maximum dose of 4.5 grams per dose.
* **Neonates (< 2 months):** Dosing in neonates is complex and should be guided by specialized pediatric infectious disease recommendations due to immature renal function.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* **3.375 g every 6 hours:** Administer 2.25 grams every 6 hours.
* **4.5 g every 6 hours:** Administer 3.375 grams every 6 hours.
* **4.5 g every 8 hours:** Administer 3.375 grams every 8 hours.
* *Note:* If the patient is on intermittent hemodialysis, administer an additional 0.75 g dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, pruritus, elevated liver enzymes (AST, ALT).
* **Serious:**
* **Hypersensitivity Reactions:** Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
* **Clostridioides difficile-associated diarrhea (CDAD).**
* **Hematologic Effects:** Neutropenia, thrombocytopenia, leukopenia, anemia, prolonged bleeding time.
* **Neurologic Effects:** Seizures (especially with high doses or renal impairment).
* **Renal Effects:** Interstitial nephritis, acute kidney injury.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** May prolong the neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin; closer INR monitoring may be necessary.
* **Aminoglycosides:** While often used together, consider physical incompatibilities and potential for antagonism in certain scenarios. Concurrent administration should be carefully considered based on the specific pathogens and clinical context.
## Monitoring
* **Renal and Liver Function:** Baseline and periodic monitoring, especially in patients with pre-existing impairment or those receiving prolonged therapy.
* **Hematologic Parameters:** Complete blood count with differential and platelet count, especially with prolonged or high-dose therapy.
* **Electrolytes:** Monitor for potential imbalances.
* **Signs and Symptoms of Hypersensitivity and CDAD.**
* **Clinical Response:** Monitor for improvement in signs and symptoms of infection.
## Clinical Pearls
* Piperacillin/tazobactam is often considered a workhorse antibiotic for serious Gram-negative infections, including those caused by *Pseudomonas aeruginosa*.
* Dosing is weight-based in pediatric patients and requires careful calculation.
* Ensure adequate hydration and monitor for electrolyte disturbances, especially with prolonged IV infusions.
* Reconstitute and dilute according to manufacturer instructions; IV infusion typically over 30 minutes. Rapid infusion may increase the risk of hypersensitivity reactions.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and relevant clinical guidelines before making therapeutic decisions.*
