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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It has broad-spectrum activity against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Bacterial infections in febrile neutropenic patients
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) intravenously every 6 hours.
* **Higher Dose:** 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) intravenously every 6 or 8 hours for more severe infections or those with suspected resistant organisms.
* **Duration of Therapy:** Typically 7 to 14 days, depending on the severity of infection and clinical response.
## Pediatric Dosing
* **Children 2 months and older:** Dosing is based on piperacillin component:
* **Serious Infections:** 80 mg/kg/dose (piperacillin component) IV every 6 hours. Maximum dose of 4 grams piperacillin per dose.
* **Febrile Neutropenia:** 100 mg/kg/dose (piperacillin component) IV every 6 hours. Maximum dose of 4 grams piperacillin per dose.
* **Duration of Therapy:** Typically 7 to 14 days.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency to every 8 hours.
* **Hemodialysis:** Administer dose every 8 hours and supplement with an additional 0.75 grams after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, phlebitis/infusion site reactions.
* **Serious:** Clostridioides difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (particularly with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** Can increase serum concentrations of piperacillin.
* **Neuromuscular Blocking Agents:** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; increased monitoring of INR is recommended.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* **Renal function:** Essential, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Monitor periodically.
* **Complete blood count:** Monitor for hematologic abnormalities (neutropenia, thrombocytopenia).
* **Signs and symptoms of infection:** Clinical response to therapy.
* **Signs and symptoms of hypersensitivity reactions.**
* **Electrolytes:** Especially in patients with prolonged therapy or significant fluid shifts.
## Clinical Pearls
* Tazobactam broadens the spectrum of piperacillin to include many beta-lactamase-producing organisms.
* Administer as a continuous infusion for higher doses (4.5g) in certain critical care settings for improved target site drug concentrations, as per institutional protocols.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated. Further dilution is required for IV infusion.
* Discontinue immediately if hypersensitivity or severe adverse reactions occur.
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*This information is intended for healthcare professionals and does not replace professional medical advice. Always consult the most current prescribing information and relevant guidelines before administering any medication.*
