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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) every 6 hours or 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) every 6 or 8 hours.
* **Dosing for *Pseudomonas aeruginosa* or severe infections:** 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) every 6 or 8 hours.
* **Maximum dose:** Generally not to exceed 18 grams per day. Dosing frequency and duration depend on the indication, severity of infection, and patient response.
## Pediatric Dosing
* **Patients 0 to 12 months:** Dosing is weight-based and often guided by institutional protocols due to limited data. A common regimen is 93.75 mg/kg (piperacillin 80 mg/kg/tazobactam 5.7 mg/kg) every 8 hours.
* **Patients 1 to 12 years:** Dosing is weight-based. A common regimen is 93.75 mg/kg (piperacillin 80 mg/kg/tazobactam 5.7 mg/kg) every 6 or 8 hours.
* **Maximum pediatric dose:** Generally not to exceed 18 grams per day, but may be higher for very large adolescents. Dosing should align with adult doses when body weight is > 50 kg or for adolescents approaching adult size.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 1/3 to 1/2 and increase dosing interval to every 8 to 12 hours. Adjustments are less critical with higher doses or continuous infusions. Hemodialysis patients usually require an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically required, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal and hepatic function.
* Signs and symptoms of infection.
* Potential hypersensitivity reactions.
* Monitor for *C. difficile* associated diarrhea.
* Complete blood count (CBC) may be monitored with prolonged therapy.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many bacterial beta-lactamases, broadening its spectrum of activity.
* Dosing frequency may be extended to every 8 hours for less severe infections or in patients with impaired renal function.
* Consider the pharmacokinetic/pharmacodynamic (PK/PD) goals for specific pathogens, particularly *Pseudomonas aeruginosa*, which may benefit from extended or continuous infusions, especially at higher doses.
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*Please consult the most current prescribing information and institutional protocols for definitive dosing and management guidelines.*
