title: Epidemiology of Acute Kidney Injury among Patients Receiving Concomitant Vancomycin and Piperacillin-Tazobactam: Opportunities for Antimicrobial Stewardship.
abstract: Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.
authors.affiliation: Department of Medicine, Detroit Medical Center, Detroit, Michigan, USA Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Karino
authors.affiliation: Department of Medicine, Detroit Medical Center, Detroit, Michigan, USA Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.affiliation: Department of Medicine, Detroit Medical Center, Detroit, Michigan, USA Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Bhagyashri
authors.initials: B
authors.lastname: Navalkele
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Bakht
authors.initials: B
authors.lastname: Nishan
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Madiha
authors.initials: M
authors.lastname: Salim
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Solanki
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Amina
authors.initials: A
authors.lastname: Pervaiz
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Tashtoush
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Hamadullah
authors.initials: H
authors.lastname: Shaikh
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Koppula
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Martin
authors.affiliation: Department of Pharmacy Services, Detroit Receiving Hospital, Detroit, Michigan, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Mynatt
authors.affiliation: Department of Pharmacy Services, Huron Valley Sinai Hospital, Detroit, Michigan, USA.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Murray
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA Department of Pharmacy Services, Detroit Receiving Hospital, Detroit, Michigan, USA Anti-Infective Research Laboratory, Department of Pharmacy Practice, Wayne State University, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan, USA Department of Pharmacy Services, Sinai-Grace Hospital, Detroit, Michigan, USA jpogue@dmc.org.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Pogue
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin; D010397:Penicillanic Acid; D010878:Piperacillin