title: Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections.
abstract: Introduction To enhance the probability of pharmacodynamic target attainment, piperacillin-tazobactam can be administered as either a continuous or extended-infusion dosage regimen for the treatment of gram-negative infections. Four hour extended-infusions of piperacillin-tazobactam 3.375 g administered intravenously (IV) every 8 h have been widely studied as an alternative to conventional, intermittent dosage regimens with largely favorable outcomes. Objective To assess the clinical and economic impact of a novel 3-h extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective cohort study before and after the implementation of an alternative dosing protocol using a 3-h infusion of piperacillin-tazobactam 3.375 g IV every 6 h. Main outcome measures The primary outcome was in-hospital mortality. Secondary outcomes include length of stay, ICU length of stay, 30-day all-cause hospital readmissions, total cost per admission, complications, and a composite of in-hospital mortality and readmission within 30 days of discharge. Results Readmission within 30 days of hospital discharge was significantly reduced in the extended-infusion arm (1.2 vs. 13.7 %, P = 0.002). A composite endpoint of death or readmission was lower among patients who received the extended-infusion dosing regimen [ORadj 0.20; 95 % CI (0.07-0.57)]. However this was likely driven by reductions in readmission. Conclusion An alternative regimen of extended-infusion piperacillin-tazobactam resulted in a significant reduction in 30-day all-cause hospital readmission. These results indicate that 3-h infusions of piperacillin-tazobactam 3.375 g IV every 6 h may represent a clinically effective alternative to other commonly used regimens and results in fewer readmissions within 30 days.
authors.affiliation: Department of Pharmacy Services, UK Healthcare, Lexington, KY, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Winstead
authors.affiliation: Department of Pharmacy Services, Saint Joseph Hospital, 1 Saint Joseph Drive, Lexington, KY, 40504, USA. ratlifpd@sjhlex.org.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Ratliff
authors.affiliation: Division of Pharmaceutical Outcomes and Policy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Hickson
authors.affiliation: Center for Health Services Research, UK Healthcare, Lexington, KY, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Mueller
authors.affiliation: Department of Pharmacy Services, Saint Joseph Hospital, 1 Saint Joseph Drive, Lexington, KY, 40504, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Judd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D007629:Kentucky / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission / Q000639:trends*; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: Antibiotics; Beta-lactams; Infectious disease; Pharmacodynamics; Pharmacology