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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination extended-spectrum penicillin (ureidopenicillin) and a beta-lactamase inhibitor. It provides broad-spectrum activity against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
## Primary Indications
* Severe pneumonia (nosocomial/ventilator-associated).
* Complicated intra-abdominal infections.
* Complicated skin and skin structure infections.
* Febrile neutropenia (often in combination with an aminoglycoside).
* Complicated urinary tract infections.
## Adult Dosing
Standard dosing for moderate to severe infections is **3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours**.
For nosocomial pneumonia or severe infections, a dosage of **4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours** is frequently used.
*Maximum daily dose:* 18 g piperacillin component per day (equivalent to 4.5 g every 6 hours). Extended or continuous infusion protocols vary by institution.
## Pediatric Dosing
Dosing for pediatric patients (≥ 9 months) is typically **80–100 mg/kg (piperacillin component) every 6–8 hours**.
* *Appendicitis/Peritonitis:* 112.5 mg/kg (piperacillin component) every 8 hours (up to 4.5 g per dose).
* *Note:* Safety and efficacy in infants < 9 months are not well-established. Always consult local hospital pediatric guidelines.
## Dose Adjustments
Renal impairment requires dosage adjustment based on CrCl (mL/min):
* **CrCl 20–40 mL/min:** 2.25 g every 6 hours.
* **CrCl < 20 mL/min:** 2.25 g every 8 hours.
* **Hemodialysis:** 2.25 g every 8 hours, with a supplemental 0.75 g after dialysis.
* *Hepatic:* No adjustment currently required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or any component of the penicillin, cephalosporin, or beta-lactamase inhibitor classes (history of anaphylaxis).
## Adverse Effects
* **Common:** Diarrhea (including *C. difficile*-associated diarrhea), constipation, nausea, insomnia, headache.
* **Serious:** Anaphylaxis, SJS/TEN (rare), seizures (especially with high doses/renal failure), cytopenias (neutropenia/thrombocytopenia with prolonged use), and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** Increases serum concentrations of piperacillin by inhibiting renal tubular secretion (avoid if possible).
* **Aminoglycosides:** Potential for physical incompatibility; infuse at separate tubing sites or different times.
* **Methotrexate:** Increased risk of toxicity due to decreased renal excretion.
* **Warfarin:** Theoretical increased risk of bleeding due to alteration of gut flora or potential platelet dysfunction.
## Monitoring
* Baseline and periodic monitoring of renal function (BUN/SCr).
* Monitor CBC with differential (if therapy exceeds 7–10 days) for signs of neutropenia.
* Monitor stool frequency for *C. difficile* colitis.
* Electrolytes (contains 2.79 mEq of sodium per gram of piperacillin).
## Clinical Pearls
* **Spectrum:** Does not cover MRSA or ESBL-producing organisms that are not inhibited by tazobactam (though it covers many ESBL-producing *E. coli*).
* **Stability:** Ensure the medication is compatible with IV fluids (usually NS or D5W).
* **Infusion:** While standard infusions are 30 minutes, extended infusions (3–4 hours) are increasingly used in ICU settings for pharmacodynamic optimization against resistant organisms.
* **Uncertainty:** Dosing for unusual pathogens or specific localized resistance profiles should always be guided by the facility's Antibiogram and the advice of an Infectious Disease specialist.
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*Disclaimer: This information is for educational purposes only and does not supersede local institutional protocols. Clinical pharmacists and providers should verify current prescribing information in the package insert or via local clinical decision support tools (e.g., Lexicomp, UpToDate) before prescribing or administering medication.*
