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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and a beta-lactamase inhibitor. Piperacillin has broad-spectrum bactericidal activity against many aerobic and anaerobic gram-positive and gram-negative bacteria, including *Pseudomonas aeruginosa*. Tazobactam inhibits most bacterial beta-lactamases, which are responsible for inactivating penicillins.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia (empiric treatment)
* Other serious infections caused by susceptible organisms
## Adult Dosing
The usual adult dose is 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) or 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) administered intravenously every 6 or 8 hours. Dosing frequency and duration depend on the severity and type of infection and clinical response.
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections, Community-Acquired Pneumonia, Hospital-Acquired Pneumonia:** Typically 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
* **Febrile Neutropenia:** Typically 4.5 grams IV every 6 hours.
* **Maximum Daily Dose:** Generally does not exceed 13.5 grams (piperacillin 12 grams) per day.
## Pediatric Dosing
* **Children 2 months and older:** Dosing is based on piperacillin component.
* **General infections:** 240 mg piperacillin/kg/day divided into 3 or 4 doses IV. Maximum daily dose of piperacillin is 16 g/day.
* **Febrile neutropenia:** 300 mg piperacillin/kg/day divided into 4 doses IV. Maximum daily dose of piperacillin is 18 g/day.
* **Note:** Consult specific institutional guidelines for precise pediatric dosing and weight-based calculations.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is required for creatinine clearance (CrCl) less than 40 mL/min.
* CrCl 20-40 mL/min: 2.25 grams IV every 6 hours (for 3.375 g total strength) or 3.375 grams IV every 6 hours (for 4.5 g total strength).
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours (for 3.375 g total strength) or 2.25 grams IV every 8 hours (for 4.5 g total strength).
* Consider intermittent hemodialysis: Administer dose after dialysis and adjust frequency.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, pruritus, fever, and injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, anaphylaxis and other hypersensitivity reactions, seizures (especially with high doses or renal impairment), leukopenia, neutropenia, thrombocytopenia, elevated liver enzymes, and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Aminoglycosides:** Concomitant use may result in chemical inactivation of aminoglycosides by piperacillin. Avoid co-administration in the same IV line; administer separately.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Signs and symptoms of infection.
* Renal and hepatic function tests, especially in patients with pre-existing impairment or receiving prolonged therapy.
* Hematologic parameters (e.g., CBC with differential, platelet count), particularly with prolonged treatment.
* Electrolytes.
* Signs of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
## Clinical Pearls
* The choice of piperacillin/tazobactam should be based on susceptibility testing when available.
* In patients with severe renal impairment, ensure adequate dosing for the indicated infection.
* Monitor for signs of electrolyte imbalance, especially in patients on diuretics or with compromised renal function, as piperacillin/tazobactam contains sodium.
* Discontinue if hypersensitivity reactions or severe adverse effects occur.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most current and comprehensive details. Dosing may vary based on institutional protocols and specific patient factors.*
