title: Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study.
abstract: This study compared treatment outcomes of adult patients with bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae (ESBL-EK) receiving flomoxef versus those receiving a carbapenem as definitive therapy. In propensity score matching (PSM) analysis, case patients receiving flomoxef shown to be active in vitro against ESBL-EK were matched with controls who received a carbapenem. The primary endpoint was 30-day crude mortality. The flomoxef group had statistically significantly higher sepsis-related mortality (27.3% vs. 10.5%) and 30-day mortality (28.8% vs. 12.8%) than the carbapenem group. Of the bacteraemic episodes caused by isolates with a MICflomoxef of ≤1 mg/L, sepsis-related mortality rates were similar between the two treatment groups (8.7% vs. 6.4%; P=0.73). The sepsis-related mortality rate of the flomoxef group increased to 29.6% and 50.0% of episodes caused by isolates with a MICflomoxef of 2-4 mg/L and 8 mg/L, respectively, which was significantly higher than the carbapenem group (12.3%). In the PSM analysis of 86 case-control pairs infected with strains with a MICflomoxef of 2-8 mg/L, case patients had a significantly higher 30-day mortality rate (38.4% vs. 18.6%). Multivariate regression analysis revealed that flomoxef therapy for isolates with a MICflomoxef of 2-8 mg/L, concurrent pneumonia or urosepsis, and a Pitt bacteraemia score ≥4 were independently associated with 30-day mortality. Definitive flomoxef therapy appears to be inferior to carbapenems in treating ESBL-EK bacteraemia, particularly for isolates with a MICflomoxef of 2-8 mg/L, even though the currently suggested MIC breakpoint of flomoxef is ≤8 mg/L.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan; Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan. Electronic address: lee900@adm.cgmh.org.tw.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan 333, Taiwan; Chang Gung University College of Medicine, 259 Wenhua 1st Road, Kweishan, Taoyuan 333, Taiwan.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Su
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan.
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan.
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Tang
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan.
authors.forename: Chia-Chin
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan.
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Chien
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan; Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan.
authors.forename: Jien-Wei
authors.initials: JW
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015780:Carbapenems / Q000627:therapeutic use*; D016022:Case-Control Studies; D002511:Cephalosporins / Q000627:therapeutic use*; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000472:pathogenicity; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D001618:beta-Lactamases; C045693:flomoxef
keywords: Case–control study; Cephamycins; Enterobacteriaceae; Mortality; Outcome; Propensity score matching