title: Appropriateness of empirical treatment and outcome in bacteremia caused by extended-spectrum-β-lactamase-producing bacteria.
abstract: We studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients with bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing bacteria in eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive patients with ESBL bacteremia (due to Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae) between 2008 and 2010. In this cohort (median age of 65 years; 24 patients were <18 years of age), many had comorbidities, such as malignancy (34%) or recurrent urinary tract infection (UTI) (15%). One hundred forty episodes (60%) were nosocomial, 54 (23%) were otherwise health care associated, and 38 (16%) were community acquired. The most frequent sources of infection were UTI (42%) and intra-abdominal infection (28%). Appropriate therapy within 24 h after bacteremia onset was prescribed to 37% of all patients and to 54% of known ESBL carriers. The day 30 mortality rate was 20%. In a multivariable analysis, a Charlson comorbidity index of ≥ 3, an age of ≥ 75 years, intensive care unit (ICU) stay at bacteremia onset, a non-UTI bacteremia source, and presentation with severe sepsis, but not inappropriate therapy within <24 h (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 0.68 to 3.45), were associated with day 30 mortality. Further assessment of confounding and a stratified analysis for patients with UTI and non-UTI origins of infection did not reveal a statistically significant effect of inappropriate therapy on day 30 mortality, and these results were insensitive to the possible misclassification of patients who had received β-lactam-β-lactamase inhibitor combinations or ceftazidime as initial treatment. In conclusion, ESBL bacteremia occurs mostly in patients with comorbidities requiring frequent hospitalization, and 84% of episodes were health care associated. Factors other than inappropriate therapy within <24 h determined day 30 mortality.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Florine N J
authors.initials: FN
authors.lastname: Frakking
authors.forename: Wouter C
authors.initials: WC
authors.lastname: Rottier
authors.forename: J Wendelien
authors.initials: JW
authors.lastname: Dorigo-Zetsma
authors.forename: Jarne M
authors.initials: JM
authors.lastname: van Hattem
authors.forename: Babette C
authors.initials: BC
authors.lastname: van Hees
authors.forename: Jan A J W
authors.initials: JA
authors.lastname: Kluytmans
authors.forename: Suzanne P M
authors.initials: SP
authors.lastname: Lutgens
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Steven F T
authors.initials: SF
authors.lastname: Thijsen
authors.forename: Annelies
authors.initials: A
authors.lastname: Verbon
authors.forename: Bart J M
authors.initials: BJ
authors.lastname: Vlaminckx
authors.forename: James W
authors.initials: JW
authors.lastname: Cohen Stuart
authors.forename: Maurine A
authors.initials: MA
authors.lastname: Leverstein-van Hall
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015897:Comorbidity; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D016972:Enterobacter cloacae / Q000187:drug effects; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases