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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination of an extended-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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 (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia (in combination with an aminoglycoside)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3.0 g piperacillin / 0.375 g tazobactam) or 4.5 grams (4.0 g piperacillin / 0.5 g tazobactam) IV every 6 hours.
* **Dosing for Severe Infections/Resistant Organisms:** Doses up to 4.5 grams IV every 4 hours or continuous infusion may be used, based on local protocols and clinical judgment.
* **Maximum Daily Dose:** Not explicitly defined, but commonly considered around 18 grams (16 g piperacillin / 2 g tazobactam) per day.
## Pediatric Dosing
* **Patients 12 years and older:** Same as adult dosing.
* **Patients younger than 12 years:** Dosing is based on piperacillin component weight-based:
* **Complicated Intra-abdominal Infections:** 90-100 mg piperacillin/kg/dose IV every 8 hours.
* **Nosocomial Pneumonia:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours.
* **Febrile Neutropenia:** 90-100 mg piperacillin/kg/dose IV every 6 or 8 hours, often given with an aminoglycoside.
* **Maximum Dose:** Generally not to exceed 4.5 g/dose or adult maximums.
* **Note:** Dosing in neonates and infants < 3 months is complex due to immature renal and hepatic function and is often guided by specialist recommendations and specific protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For 6-hour dosing intervals, increase to 8-hour intervals. For 4-hour dosing intervals, increase to 6-hour intervals. If on hemodialysis, administer after dialysis and increase frequency to every 8 hours.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, elevated liver enzymes.
* **Serious:** Anaphylaxis, Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular Blocking Agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Bacteriostatic Antibiotics:** May antagonize the effect of piperacillin-tazobactam.
## Monitoring
* **Renal function:** Monitor serum creatinine and adjust dosing as needed.
* **Liver function:** Monitor LFTs periodically.
* **Hematologic parameters:** Monitor CBC, especially with prolonged therapy or in renal impairment.
* **Electrolytes:** Monitor electrolytes, particularly in patients with diarrhea or those receiving IV fluids.
* **Signs of hypersensitivity:** Monitor for rash, pruritus, and bronchospasm.
* **Signs of CDAD:** Monitor for persistent diarrhea.
* **Therapeutic response:** Monitor for improvement in signs and symptoms of infection.
## Clinical Pearls
* The presence of tazobactam broadens the spectrum of activity against beta-lactamase producing organisms, including many Gram-negative and anaerobic pathogens.
* For severe infections or infections caused by less susceptible organisms, a continuous infusion may be considered to maintain higher drug concentrations. This typically involves administering the total daily dose over 24 hours. Specific protocols for continuous infusion should be followed.
* Reconstituted solutions are generally stable for 24 hours at room temperature or 48 hours refrigerated. Check manufacturer's specific recommendations.
* When using in combination therapy (e.g., febrile neutropenia), administer agents separately if using specific combinations (e.g., aminoglycosides and penicillins may inactivate each other).
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*This information is intended for healthcare professionals. Always consult the official prescribing information and institutional protocols for complete details and to verify current recommendations before prescribing.*
