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# Piperacillin/Tazobactam ## Overview Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria. ## Primary Indications * Complicated intra-abdominal infections * Complicated skin and skin structure infections * Community-acquired pneumonia * Hospital-acquired pneumonia * Febrile neutropenia (empiric treatment) ## Adult Dosing * **Standard dose:** 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) IV every 6 hours. * **Dose for severe infections or *Pseudomonas aeruginosa*:** 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) IV every 6 or 8 hours. * **Maximum dose:** Generally not to exceed 18 grams per day (piperacillin 16 grams/tazobactam 2 grams). * **Infusion:** Administer over 30 minutes. Extended infusion (e.g., 4 hours) may be considered for critically ill patients to optimize pharmacokinetic/pharmacodynamic targets, but this is subject to institutional protocol. ## Pediatric Dosing Dosing is typically based on the piperacillin component. * **Children 2 to 12 months:** 80 mg piperacillin/10 mg tazobactam per kg per dose IV every 6 hours. * **Children 1 to 12 years:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours. * **Maximum pediatric dose:** Generally, not to exceed the adult dose of 4.5 grams per dose. * **Infants < 2 months:** Dosing is not well established and should be individualized based on gestational and postnatal age, weight, and renal function. Consultation with a pediatric infectious disease specialist or pharmacist is recommended. ## Dose Adjustments * **Renal Impairment:** * CrCl > 40 mL/min: No dose adjustment needed. * CrCl 20-40 mL/min: Reduce dose by 25% or increase interval to every 8 hours. * CrCl < 20 mL/min: Reduce dose by 50% or increase interval to every 8-12 hours. * *Note:* Dosing is complex and may vary. Consult specific guidelines or pharmacist. ## Contraindications * Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors. * History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use. ## Adverse Effects * **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, elevated liver enzymes. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), Stevens-Johnson syndrome/toxic epidermal necrolysis, seizures (especially with high doses or renal impairment), interstitial nephritis, neutropenia, thrombocytopenia. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels. * **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium. * **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely. * **Aminoglycosides:** While synergistic, co-administration can lead to physical inactivation of piperacillin/tazobactam if mixed in the same IV line. Administer separately. ## Monitoring * **Renal function:** Monitor serum creatinine and adjust dose as needed, especially in patients with pre-existing renal impairment or receiving other nephrotoxic agents. * **Liver function:** Monitor liver enzymes periodically, particularly with prolonged therapy. * **Hematologic parameters:** Monitor CBC for potential neutropenia or thrombocytopenia, especially with prolonged or high-dose therapy. * **Signs and symptoms of infection:** Clinical response to therapy. * **Signs of hypersensitivity:** Monitor for rash, pruritus, or signs of anaphylaxis. ## Clinical Pearls * Tazobactam expands the spectrum of piperacillin by inhibiting many beta-lactamases, including those produced by *Pseudomonas aeruginosa* and many anaerobes. * Dosing frequency and duration should be guided by the severity and type of infection, pathogen susceptibility, and clinical response. * Electrolyte imbalances can occur, particularly with high doses. * Consider the potential for cross-reactivity in patients with penicillin allergies. *** **Disclaimer:** This information is intended for clinical use and is a summary. Always consult the most current prescribing information, institutional protocols, and relevant literature before making clinical decisions.