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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination of an extended-spectrum penicillin-class antibacterial and a beta-lactamase inhibitor. It is bactericidal against susceptible organisms.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
* Certain other moderate to severe bacterial infections caused by susceptible organisms, including those producing beta-lactamase.
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV).
* **Higher Dose:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV, depending on indication and severity.
* **Maximum:** Not explicitly defined, but higher doses are used for severe infections.
## Pediatric Dosing
* **Children 0 to < 12 years:** Dosing is based on piperacillin component, typically 80 to 100 mg/kg/day divided into 4 doses (every 6 hours) IV. The tazobactam component is usually given at a 1:8 ratio with piperacillin. **Dosing requires careful calculation based on weight and indication and should adhere to institutional protocols.**
* **Children ≥ 12 years:** Generally dosed as per adult.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 33% to 50% and increase dosing interval to every 8 hours. For CrCl 20-50 mL/min, consider extending interval or reducing dose per institutional guidelines. Dosing based on piperacillin component.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or any component of the formulation.
* History of immediate or severe allergic reaction to beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, phlebitis at the injection site.
* **Serious:** *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures (especially at high doses or in renal impairment), hemolytic anemia, interstitial nephritis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
## Key Drug Interactions
* **Probenecid:** Increases and prolongs piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents:** May prolong the neuromuscular blockade.
* **Warfarin:** May decrease warfarin's anticoagulant effect; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
* **Aminoglycosides:** Potentially synergistic, but physical incompatibilities exist; administer separately.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests
* Electrolytes
* Complete blood count (CBC)
* Signs and symptoms of infection (fever, WBC count, cultures)
* Signs of hypersensitivity or severe adverse reactions.
* INR if patient is on warfarin.
## Clinical Pearls
* The ratio of piperacillin to tazobactam is typically 8:1.
* Duration of therapy depends on the severity and type of infection and clinical response.
* Can be administered as a continuous infusion for critically ill patients, which may achieve higher drug exposure and potentially reduce the risk of resistance. Dosing for continuous infusion differs and should follow institutional guidelines.
* Discontinue if patient develops a severe rash or other signs of hypersensitivity.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols before administering any medication. Drug information is constantly evolving.*
