Tazobactum%2525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520piperacillin

# Piperacillin-Tazobactam ## Overview Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, and tazobactam, a beta-lactamase inhibitor. 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 * Nosocomial pneumonia * Febrile neutropenia (empiric treatment) ## Adult Dosing * **Standard Dose:** 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 6 hours. * **Severe Infections/Higher Inoculum:** 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 hours. * **Maximum Dose:** Generally, the maximum recommended dose is 4.5 grams every 6 hours. In some cases of severe infections or for higher bacterial burdens, extended-infusion regimens may be utilized per institutional guidelines, potentially increasing the total daily dose. *Note: Dosing frequency and duration are dependent on the severity of infection, pathogen susceptibility, and clinical response. Specific dosing for febrile neutropenia may vary based on institutional protocols.* ## Pediatric Dosing * **Children 2 months and older:** * **Standard Dose:** 2.4 grams/0.3 grams (piperacillin 2 grams / tazobactam 0.25 grams) per 100 mL of D5W or NS infused over 30 minutes every 6 hours. * **Severe Infections/Higher Inoculum:** 3.6 grams/0.45 grams (piperacillin 3 grams / tazobactam 0.375 grams) per 100 mL of D5W or NS infused over 30 minutes every 6 hours. *Note: Dosing for neonates and infants under 2 months is not well established and requires expert consultation. Dosing is typically based on weight (e.g., 80-100 mg piperacillin equivalent/kg/dose).* ## Dose Adjustments * **Renal Impairment (CrCl < 20 mL/min):** Reduce the frequency of administration. Typically, a dose every 8 hours is recommended for the standard 3.375 g dose. For the 4.5 g dose, frequency reduction is also necessary. Further adjustments may be needed based on the severity of renal impairment and the specific dose regimen. * **Hemodialysis:** Patients on hemodialysis should receive the dose after dialysis and may require dosing every 8 hours. * **Hepatic Impairment:** No dose adjustment is typically required. ## Contraindications * Hypersensitivity to piperacillin, tazobactam, other penicillins, or any component of the formulation. * History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, elevated liver enzymes (AST, ALT). * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, leukopenia, interstitial nephritis, and superinfections. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin-tazobactam plasma concentrations. * **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** May decrease the anticoagulant effect of warfarin; monitor INR closely. * **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels. ## Monitoring * Renal function (BUN, creatinine) * Liver function tests (AST, ALT) * Complete blood count (CBC), especially during prolonged therapy, for hematologic effects. * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of *Clostridioides difficile*-associated diarrhea. * Clinical response to therapy. ## Clinical Pearls * Piperacillin-tazobactam covers many common hospital-acquired pathogens, including *Pseudomonas aeruginosa*. * Tazobactam extends the spectrum of piperacillin by inhibiting many beta-lactamases. * Extended infusion (e.g., over 4 hours) may improve outcomes in critically ill patients with infections due to *Pseudomonas aeruginosa*. * Monitor for potential electrolyte disturbances (especially in patients with renal impairment or receiving large fluid volumes). * Bicarbonate should not be added to the infusion fluid as it may degrade piperacillin. *** *This information is intended for healthcare professionals. Always verify current prescribing information and consult with a pharmacist or physician for specific patient care decisions.*