title: Controlling for severity of illness in outcome studies involving infectious diseases: impact of measurement at different time points.
abstract: BACKGROUND
  Severity of illness is an important confounder in outcome studies involving infectious diseases. However, it is unclear whether the time at which severity of illness is measured is important.
  
  
  METHODS
  We performed a retrospective study of 328 episodes of gram-negative bacteremia in adult patients to assess the impact of the time of measurement of severity of illness on the association between empirical antimicrobial therapy received and in-hospital mortality. Using a modified Acute Physiology Score (APS), severity of illness was measured at 2 time points: (1) hospital admission and (2) 24 hours before the first culture-positive blood sample was collected. Multivariate logistic regression was used to estimate the impact of adjusting for the APS on the relationship between empirical therapy received (ie, the exposure) and in-hospital mortality (ie, the outcome).
  
  
  RESULTS
  The mean APS (+/- standard deviation) of patients with bacteremia increased during their hospital stay (from 19.2 +/- 11.6 at admission to 24.2 +/- 13.6 at the second time point; P < .01). When examining the association between empirical antimicrobial therapy received and in-hospital mortality, and controlling for the APS, there was a trend toward a decreased impact of appropriate therapy received on in-hospital mortality. The unadjusted odds ratio (OR) for the association between appropriate therapy received and in-hospital mortality was 0.83 (95% confidence interval [CI], 0.51-1.34). After controlling for the APS at admission, this association was attenuated (OR, 0.94 [95% CI, 0.57-1.55]), and when a change in the APS was also included in the multivariate logistic regression model, the association was further attenuated (OR, 0.99 [95% CI, 0.58-1.69]).
  
  
  CONCLUSIONS
  The magnitude of the association between appropriate antimicrobial therapy received and in-hospital mortality among patients with gram-negative bacteremia was sensitive to the timing of adjustment for severity of illness.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. kthoms@medicine.umaryland.edu
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Thom
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Shardell
authors.forename: Regina B
authors.initials: RB
authors.lastname: Osih
authors.forename: Marin L
authors.initials: ML
authors.lastname: Schweizer
authors.forename: Jon P
authors.initials: JP
authors.lastname: Furuno
authors.forename: Eli N
authors.initials: EN
authors.lastname: Perencevich
authors.forename: Jessina C
authors.initials: JC
authors.lastname: McGregor
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000145:classification / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D003428:Cross Infection / Q000145:classification / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents