title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: D'Agostino
authors.affiliation: Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA; Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA.
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Rhodes
authors.affiliation: Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Skoglund
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA; Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA. Electronic address: mscheetz@nm.org.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Scheetz
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy* / Q000209:etiology; D004696:Endocarditis / Q000209:etiology / Q000628:therapy*; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D001618:beta-Lactamases / Q000097:blood*; D047090:beta-Lactams / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; C558534:beta-lactamase GOB-1, Elizabethkingia meningoseptica; D010878:Piperacillin
keywords: Extended-infusion; Gram-negative bloodstream infection; Minimum inhibitory concentration; Pharmacokinetic model; Piperacillin-tazobactam; Standard infusion