Microbiologic clearance following transition from standard infusion piperacillin-tazobactam to extended-infusion for persistent Gram-negative bacteremia and possible endocarditis: A case report and review of the literature.

Introduction: We sought to describe a case of pharmacodynamically-optimized dosing of piperacillin-tazobactam in a patient that cleared their infections after treatment with high-dose, extended-infusion piperacillin-tazobactam and summarize the literature on the benefits of extended-infusion of beta-lactams.

Case Report: At an outside hospital, a 78 year-old male presented with fevers and shortness of breath. He was empirically initiated on standard doses of vancomycin and piperacillin-tazobactam for suspected pneumonia and sepsis. Blood and sputum cultures identified Elizabethkingia meningosepticum sensitive only to piperacillin-tazobactam by E-test susceptibility testing. After 10 days of empiric therapy with piperacillin-tazobactam dosed at 3.375 g IV every 8 h over 30 min, the patient transferred to our institution and was initiated on piperacillin-tazobactam at 3.375 g IV every 8 h administered as a 4 h infusion. The patient failed to improve; piperacillin-tazobactam was changed to 4.5 g IV over 4 h every 8 h and later changed to the hospital protocol dose of 3.375 g IV over 4 h every 6 h. The patient achieved negative blood cultures within 24 h of optimized dosing.

Discussion: We present the first case to our knowledge that describes failure to respond and subsequent response within a single patient where beta-lactam dosing was altered to optimize pharmacokinetics and pharmacodynamics (PK-PD). Our patient received non-standard dose-escalation for piperacillin-tazobactam. Drug exposure was estimated post-hoc utilizing robust mathematical simulations to describe alterations in disposition over time. This case demonstrates that extended-infusion administration of beta-lactams may provide improved microbiological activity.