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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many beta-lactamase enzymes, thereby extending its spectrum of activity.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin-structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
* Bacterial infections known or suspected to be caused by piperacillin-resistant, beta-lactamase producing Gram-negative organisms (e.g., *Pseudomonas aeruginosa*) in combination with appropriate Gram-positive or anaerobic coverage.
## Adult Dosing
The recommended dose is typically 3.375 grams (piperacillin 3g/tazobactam 0.375g) or 4.5 grams (piperacillin 4g/tazobactam 0.5g) administered intravenously every 6 or 8 hours.
* **Complicated intra-abdominal infections, complicated skin and skin-structure infections, community-acquired pneumonia, and nosocomial pneumonia:** Commonly dosed at 4.5 grams IV every 6 hours.
* **Febrile neutropenia:** Commonly dosed at 4.5 grams IV every 6 hours. Duration of therapy depends on clinical response and resolution of neutropenia.
* **Serious infections or infections caused by less susceptible organisms:** Doses up to 4.5 grams IV every 4 hours may be considered, up to a maximum of 18 grams per day (piperacillin component).
Specific duration of therapy depends on the type and severity of infection, as well as the clinical and bacteriologic response, and should be guided by local protocols.
## Pediatric Dosing
Dosing in pediatric patients is based on the piperacillin component and is weight-based.
* **Patients 2 months of age and older:**
* **Complicated intra-abdominal infections:** 90 mg piperacillin/11.25 mg tazobactam per kg of body weight administered IV every 8 hours.
* **Complicated skin and skin-structure infections:** 90 mg piperacillin/11.25 mg tazobactam per kg of body weight administered IV every 8 hours.
* **Complicated intra-abdominal infections and complicated skin and skin-structure infections in patients weighing over 40 kg:** Administer as per adult dosing regimen (e.g., 3.375 g or 4.5 g every 6 or 8 hours).
* **For patients with severe infections or infections caused by less susceptible organisms:** Doses up to 120 mg piperacillin/15 mg tazobactam per kg of body weight administered IV every 6 hours may be considered.
* **Maximum dose:** Dosing should not exceed the maximum adult dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment.
* CrCl 20-40 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) or 3.375 grams (piperacillin 3g/tazobactam 0.375g) IV every 8 hours (if using 3.375g every 6h regimen), or 3.375 grams IV every 8 hours (if using 4.5g every 8h regimen).
* CrCl < 20 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) IV every 8 hours or 3.375 grams IV every 12 hours.
* **Hemodialysis:** Administer dose after dialysis and supplement with an additional dose. Dosage adjustments should be guided by local protocols.
* **Hepatic Impairment:** No specific dose adjustment is usually recommended, but caution is advised.
## Contraindications
* Known history of severe allergic reaction to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, phlebitis/thrombophlebitis, elevated liver enzymes.
* **Serious:** Anaphylaxis and other severe hypersensitivity reactions, *Clostridioides difficile*-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic changes (leukopenia, neutropenia, eosinophilia, thrombocytopenia), hepatic dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** Piperacillin may decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Bacteriostatic agents (e.g., tetracyclines, macrolides):** May antagonize the bactericidal effect of penicillins.
## Monitoring
* Renal function (especially with impaired renal function or concomitant nephrotoxic agents).
* Liver function tests.
* Hematologic parameters (complete blood count) during prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Clinical and bacteriologic response to therapy.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including coverage against *Pseudomonas aeruginosa*.
* Tazobactam extends the spectrum of piperacillin against many beta-lactamase producing organisms, but not all (e.g., some extended-spectrum beta-lactamases (ESBLs), carbapenemases). Susceptibility testing is crucial.
* Reconstituted solutions should be used within recommended timeframes due to potential for bacterial growth and degradation.
* Infusion-related reactions (e.g., phlebitis) can occur; consider slow infusion rates and rotating infusion sites.
* Sodium content: Each gram of piperacillin/tazobactam contains approximately 1.12 mmol of sodium. This should be considered in patients requiring sodium restriction.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete and up-to-date drug information, including indications, contraindications, warnings, precautions, adverse reactions, drug interactions, and dosing.
