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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor. It provides broad-spectrum coverage against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Intra-abdominal infections (e.g., appendicitis, peritonitis)
* Nosocomial/Hospital-acquired pneumonia
* Skin and skin structure infections
* Empiric therapy for febrile neutropenia
## Adult Dosing
The standard dosage is **3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 6 hours**.
* **Severe infections:** 4.5 g (4 g piperacillin / 0.5 g tazobactam) IV every 6 or 8 hours.
* **Maximum:** 18 g piperacillin/2.25 g tazobactam per 24 hours.
* **Administration:** Typically infused over 4 hours for critically ill patients to optimize pharmacodynamics (time above MIC).
## Pediatric Dosing
Dosing varies significantly by age and indication; consult institutional guidelines.
* **Children 9 months and older:** 100 mg piperacillin/kg/dose every 8 hours (or 80 mg/kg/dose every 6 hours).
* **Febrile Neutropenia:** 80–100 mg piperacillin/kg/dose every 6–8 hours (max 4 g piperacillin per dose).
## Dose Adjustments
* **Renal Impairment:** Required for CrCl ≤40 mL/min. Dosing is highly dependent on the degree of impairment and dialysis modality. Always consult a standardized renal dosing tool (e.g., Lexicomp or institutional protocol).
* **Hepatic Impairment:** No standard adjustment required, but use with caution.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or any beta-lactam antibiotic (history of anaphylaxis or severe skin reactions).
## Adverse Effects
* **Common:** Diarrhea, nausea, constipation, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), severe hypersensitivity/anaphylaxis, bone marrow suppression (leukopenia/neutropenia with prolonged use), and seizures (primarily in renal failure).
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides (physicochemical incompatibility); infuse at separate times or separate lines.
* **Methotrexate:** Increased serum concentrations/toxicity risk.
* **Warfarin:** Theoretical increased risk of bleeding due to alteration of gut flora or potential platelet dysfunction.
* **Probenecid:** Increases serum concentrations of piperacillin.
## Monitoring
* **Renal function:** Monitor BUN/SCr.
* **Hematologic:** Monitor CBC with differential, especially if therapy exceeds 10–14 days (risk of neutropenia).
* **Clinical:** Resolution of signs of infection; monitor for signs of CDAD (diarrhea).
## Clinical Pearls
* **Spectrum:** Does not cover MRSA or atypical organisms (*Legionella, Mycoplasma, Chlamydia*).
* **Stability:** Ensure correct preparation and compatibility with IV fluids (typically NS or D5W).
* **Sodium Load:** Each 4.5 g dose contains 2.35 mEq (approximately 54 mg) of sodium; consider in patients on strict sodium restriction.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice and institutional protocols vary. Always verify current prescribing information, package inserts, and local organizational guidelines before prescribing or administering medication.
