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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is effective 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
* Febrile neutropenia (in combination with an aminoglycoside, if indicated)
## Adult Dosing
Standard dose: 3.375 g every 6 hours or 4.5 g every 8 hours administered intravenously over 30 minutes.
Maximum daily dose: Not explicitly defined but typically based on the highest recommended q6h or q8h regimen. Some sources suggest up to 18 g/day. Actual maximum may depend on local institutional guidelines and severity of infection.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Children 2 months to 12 years:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered intravenously every 8 hours.
* **Children 2 months to 12 years with severe infections or nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered intravenously every 6 hours.
* **Maximum dose:** 4.5 g per dose. For children weighing >40 kg, use adult dosing if it provides a lower dose than calculated pediatric dose to avoid exceeding adult maximums.
* Dosing for neonates and infants younger than 2 months is not well established and should be guided by specific institutional protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):**
* 3.375 g q6h: Reduce to 2.25 g q6h.
* 4.5 g q8h: Reduce to 3.375 g q8h.
* **Hemodialysis:** Administer dose every 8 hours. An additional dose of 0.75 g should be administered after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is recommended, but monitor hepatic function.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of biliary dysfunction associated with piperacillin-tazobactam therapy.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, elevated liver enzymes (AST, ALT), eosinophilia, thrombocytopenia, leukopenia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hemolytic anemia, hepatic dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Live typhoid vaccine:** Inactivated by antibiotics.
## Monitoring
* Renal function (BUN, serum creatinine).
* Liver function tests (AST, ALT, bilirubin).
* Hematologic parameters (CBC with differential, platelet count).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Prothrombin time/INR if co-administered with warfarin.
* Therapeutic drug monitoring for methotrexate if co-administered.
## Clinical Pearls
* Administer over 30 minutes to minimize infusion site reactions.
* Consider switching to oral therapy once clinically stable and appropriate.
* Tazobactam itself has minimal antibacterial activity; its primary role is to protect piperacillin from degradation by beta-lactamases.
* The reconstituted solution has limited stability and should be used promptly. Refer to manufacturer's guidelines for storage.
* Dosing in critically ill patients or those with severe infections may require higher doses and/or more frequent administration, guided by clinical response and local protocols.
*Disclaimer: This information is intended for clinical use and does not replace professional judgment. Always consult the most current prescribing information and institutional guidelines for definitive guidance.*
