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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against a broad spectrum of 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
* Nosocomial pneumonia
* Febrile neutropenia (in combination regimens)
## Adult Dosing
The typical dose is 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours, or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. The choice of regimen depends on the severity and type of infection. Dosing frequency may be extended to every 8 hours for less severe infections or for prolonged intermittent infusions. Maximum daily dose is generally considered 18 grams. Actual dosing regimens can vary based on institutional protocols and specific indications.
## Pediatric Dosing
For patients 2 months and older:
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight intravenously every 8 hours.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight intravenously every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight intravenously every 8 hours.
Maximum dose in pediatrics is typically limited to the adult maximum of 4.5 grams per dose. Specific recommendations may vary for younger infants.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Reduce dose or prolong interval. Common regimens include 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours or 3.375 grams (3g piperacillin/0.375g tazobactam) every 8 hours for CrCl 20-40 mL/min. For CrCl < 20 mL/min, doses of 2.25 grams every 8 hours are often used. Dosing in ESRD (hemodialysis) is typically 2.25 grams every 8 hours, with an additional dose after dialysis.
## Contraindications
* Known serious allergic reaction to piperacillin, tazobactam, other penicillins, or beta-lactams (including cephalosporins and carbapenems).
## Adverse Effects
Common adverse effects include diarrhea, rash, nausea, vomiting, headache, insomnia, and abdominal pain. More serious adverse effects include hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with renal impairment or high doses), neutropenia, thrombocytopenia, and elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the action of vecuronium.
* **Oral anticoagulants (e.g., warfarin):** Increased risk of bleeding. Monitor INR closely.
* **Methotrexate:** Penicillins may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially in patients with pre-existing renal impairment or receiving nephrotoxic agents).
* Liver function tests.
* Hematologic parameters (e.g., CBC with differential, platelet count) with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Tazobactam broadens the spectrum of piperacillin to include many beta-lactamase-producing organisms.
* Administer by intravenous infusion over at least 30 minutes. Prolonged or rapid infusions may increase the incidence of seizures.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Adjust dose based on renal function.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and institutional guidelines for complete details before making any clinical decisions. Dosing and recommendations may vary.*
