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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination extended-spectrum penicillin (ureidopenicillin) and a beta-lactamase inhibitor. It provides coverage against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
## Primary Indications
* Moderate-to-severe systemic or local infections (e.g., intra-abdominal, skin and skin structure, pneumonia).
* Febrile neutropenia (commonly as empirical monotherapy).
* Nosocomial or ventilator-associated pneumonia.
## Adult Dosing
The standard dosage is **3.375 g to 4.5 g (piperacillin/tazobactam) IV every 6 hours**.
* **Renal/Severe Infections:** 4.5 g IV every 6 or 8 hours.
* **Method of Administration:** Typically infused over 30 minutes; however, extended infusion (4 hours) is frequently employed in ICU settings for organisms with high MICs (consult local institutional guidelines).
## Pediatric Dosing
* **Neonates (≤ 40 weeks postmenstrual age):** 80–120 mg/kg/day (piperacillin component), divided every 8–12 hours.
* **Pediatrics (≥ 9 months):** 240–300 mg/kg/day (piperacillin component), divided every 6–8 hours.
* **Max Dose:** 4.5 g per dose (18 g piperacillin/day).
## Dose Adjustments
Dosing **must** be reduced in renal impairment (calculated CrCl).
* **CrCl 20–40 mL/min:** 2.25–3.375 g every 6–8 hours.
* **CrCl < 20 mL/min:** 2.25–2.25 g every 8–12 hours.
* **Hemodialysis:** Supplementation is required; typically 0.75 g post-dialysis, but refer to institutional renal dosing protocols.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, or any component of the penicillin, cephalosporin, or beta-lactamase inhibitor classes (due to potential cross-reactivity).
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, injection site reaction.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis), rash (e.g., DRESS, SJS/TEN), leukopenia, neutropenia, and thrombocytopenia (especially with prolonged therapy > 14 days).
## Key Drug Interactions
* **Aminoglycosides:** May cause physical inactivation if mixed in the same IV line. Monitor for nephrotoxicity when used in combination.
* **Probenecid:** Increases serum concentrations of piperacillin.
* **Warfarin:** May enhance anticoagulant effects due to disruption of gut flora or impact on platelet function.
* **Methotrexate:** May decrease renal clearance, increasing risk of toxicity.
## Monitoring
* **Renal:** Monitor serum creatinine and urine output.
* **Hematologic:** Monitor CBC with differential, particularly platelets and neutrophils if therapy exceeds 10–14 days.
* **Clinical:** Resolution of signs/symptoms of infection and daily review of culture/sensitivity reports (de-escalate where appropriate to narrow-spectrum agents).
* **Electrolytes:** Monitor for hypokalemia, as high doses provide significant sodium load.
## Clinical Pearls
* **Sodium Load:** Each 4.5 g dose contains approximately 11.2 mEq (257 mg) of sodium; use caution in patients with heart failure or hypertension.
* **Stewardship:** High utility "big gun" antibiotic; consider narrowing therapy promptly once susceptibility profiles are available to mitigate selection of resistant organisms.
* **IV Compatibility:** Physically incompatible with many drugs (e.g., amiodarone, amphotericin B); flush lines thoroughly when switching between infusions.
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*Disclaimer: This information is for educational purposes only. Always consult your current institutional guidelines and the full prescribing information before dosing or administering any medication.*
