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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
* **Duration:** Typically 7-14 days, depending on the infection and clinical response.
* **Maximum Daily Dose:** 18 grams (for severe infections, typically reserved for specific indications like febrile neutropenia, and requires careful consideration).
## Pediatric Dosing
* **Children weighing < 40 kg:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 6 hours.
* **Children weighing ≥ 40 kg:** Same as adult dosing.
* **Neonates and Infants < 2 months:** Dosing is complex and often based on gestational and chronological age, requiring specific consultation or protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 33% to 50% and extend interval to every 8 hours.
* **Hemodialysis:** Administer dose after dialysis and supplement with an additional 0.75 grams dose.
* **Hepatic Impairment:** No dose adjustment typically needed.
## Contraindications
* History of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate and severe allergic reaction to penicillin.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Increased serum creatinine and BUN
* Elevated liver enzymes (AST, ALT)
* Thrombocytopenia, neutropenia, eosinophilia
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR.
* **Methotrexate:** May decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically)
* Liver function tests (baseline and periodically)
* Complete blood count (especially with prolonged therapy or suspected hematologic toxicity)
* Signs and symptoms of infection and hypersensitivity reactions
* Electrolytes
## Clinical Pearls
* Reconstitute and dilute according to manufacturer instructions.
* Administer IV infusion over at least 30 minutes. Avoid rapid infusion.
* Tazobactam itself has minimal antibacterial activity but extends the spectrum of piperacillin by inhibiting beta-lactamases.
* Consider the potential for *Clostridioides difficile*-associated diarrhea.
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This information is intended for clinical decision support and does not replace the need to consult the most current prescribing information and institutional protocols. Always verify drug information with up-to-date resources before administration.
