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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many bacterial beta-lactamases, extending its spectrum of activity to include many Gram-negative bacteria that produce these enzymes.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
* Documented or suspected infections due to piperacillin-resistant Gram-negative organisms, including *Pseudomonas aeruginosa*, or beta-lactamase-producing Gram-negative bacteria.
## Adult Dosing
Standard dose: 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) IV every 6 hours.
Extended infusion: 3.375 grams or 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) IV infused over 4 hours every 6 or 8 hours.
Maximum dose: Typically not to exceed 13.5 grams (piperacillin 12 grams / tazobactam 1.5 grams) per day. Specific dosing regimens may vary based on indication, severity, and local antibiogram.
## Pediatric Dosing
Dosing varies significantly by age and indication.
* **Neonates and infants < 1 year:** 100 mg piperacillin / 12.5 mg tazobactam per kg IV every 8 to 12 hours, depending on gestational and postnatal age.
* **Children 1 to 12 years:** 75 mg piperacillin / 9.375 mg tazobactam per kg IV every 6 or 8 hours, not to exceed the adult dose of 3.375 grams per dose.
* **Children weighing > 50 kg:** Generally dose as adults.
* **Children with febrile neutropenia:** 100 mg piperacillin / 12.5 mg tazobactam per kg IV every 8 hours.
Note: Specific pediatric dosing recommendations should be confirmed with institutional protocols or specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:** Dose reduction or increased dosing interval is required for CrCl < 50 mL/min.
* CrCl 20-50 mL/min: 2.25 g IV every 6 hours.
* CrCl < 20 mL/min: 2.25 g IV every 8 hours.
* Hemodialysis: 2.25 g IV every 8 hours plus an additional dose (2.25 g) after each hemodialysis session.
## Contraindications
* History of any severe allergic reaction (e.g., anaphylaxis) to piperacillin, tazobactam, other beta-lactam antibiotics, or penicillin.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Fever, phlebitis/thrombophlebitis
* Elevated liver enzymes (AST, ALT)
* Hypokalemia
* Seizures (rare, particularly with high doses or renal impairment)
* Anaphylaxis and other severe hypersensitivity reactions.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin, requiring closer INR monitoring.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests (LFTs) periodically.
* Electrolytes, especially potassium.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile-associated diarrhea.
* Culture and sensitivity results to guide therapy duration.
## Clinical Pearls
* Consider extended infusion (over 4 hours) for improved efficacy, especially against *Pseudomonas aeruginosa*.
* Risk of C. difficile-associated diarrhea; monitor stool for loose or watery stools.
* Cross-reactivity with other beta-lactam antibiotics can occur.
* Adequate hydration is important, especially with IV administration, to minimize CNS side effects (e.g., seizures) in patients with renal impairment.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols before administering this medication. Dosage and administration may vary based on patient-specific factors and clinical context.
