Association Between Time to Appropriate Antimicrobial Treatment and 30-day Mortality in Patients With Bloodstream Infections: A Retrospective Cohort Study

Abstract

Background: Effective antimicrobial treatment is key for survival in bloodstream infection (BSI), but the impact of timing of treatment remains unclear. Our aim was to assess the association between time to appropriate antimicrobial treatment and 30-day mortality in BSI patients.

Methods: This was a retrospective cohort study using electronic health record data from a large academic center in Sweden. Adult patients admitted between the years 2012 and 2019, with onset of BSI at the emergency department or general wards, were included. Pathogen-antimicrobial drug combinations were classified as appropriate or inappropriate based on reported in vitro susceptibilities. To avoid immortal time bias, the association between appropriate therapy and mortality was assessed with multivariable logistic regression analysis at pre-specified landmark times.

Results: We included 10 628 BSI-episodes, occurring in 9192 unique patients. The overall 30-day mortality was 11.8%. No association in favor of a protective effect between appropriate therapy and mortality was found at the 1, 3 and 6 hours landmark after blood culture collection. At 12 hours, the risk of death increased with inappropriate treatment (adjusted odds ratio 1.17 [95% confidence interval {CI}, 1.01-1.37]) and continued to increase gradually at 24, 48, and 72 hours. Stratifying by high or low SOFA score generated similar odds ratios, with wider confidence intervals.

Conclusions: Delays in appropriate antimicrobial treatment were associated with increased 30-day mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours, in BSI. These results indicate a benchmark for providing rapid microbiological diagnostics of blood cultures.

Keywords: antimicrobial treatment; bloodstream infection; mortality.

Figure 1.

Schematic figure illustrates the time varying exposure of appropriate treatment. Patients being switched to appropriate treatment at a later time had guaranteed survival to this time point. To avoid immortal time bias, only patients surviving to the landmark time of interest were included in the analysis. At each landmark time, exposure was classified according to the present treatment, irrespectively of if they were later switched to appropriate treatment.

Figure 2.

Study cohort flowchart. The final cohort consisted of 10 628 BSI episodes occurring in 9192 unique patients. Abbreviations: BSI, bloodstream infection; SOFA, sequential organ failure assessment score.

Figure 3.

Overview of pathogens retrieved in blood cultures (n = 12 223) and the proportion of appropriate and inappropriate antimicrobial treatment at 24 h. The proportion of pathogen-antimicrobial drug combinations which could not be determined as either appropriate or inappropriate based on the surrogate antibiogram are shown as undetermined. Only pathogens with a prevalence >1% are shown and the remaining pathogens are grouped as “other.” Abbreviations: B. fragilis group, Bacteroides fragilis group; beta-hemolytic S., beta-hemolytic Streptococcus; coagulase-negative S., coagulase-negative Staphylococcus; E. cloacae, Enterobacter cloacae; E. faecalis, Enterococcus faecalis; E. faecium, Enterococcus faecium; E. coli, Escherichia coli; K. oxytoca, Klebsiella oxytoca; K. pneumoniae; Klebsiella pneumoniae; P. mirabilis, Proteus mirabilis; P. aeruginosa, Pseudomonas aeruginosa; S. aureus, Staphylococcus aureus; S. pneumoniae, Streptococcus pneumoniae; viridans S., viridans streptococci.

Figure 4.

Association of time to appropriate treatment with mortality at specified landmark times. High SOFA score was defined as ≥2 points and low SOFA score was defined as <2 points. Only patients with determined pathogen-antimicrobial drug combinations were analysed at each landmark time of interest. Associations were estimated using logistic regression with adjustments for age, sex, Charlson comorbidity index, immunosuppression, SOFA score, polymicrobial bloodstream infection, source of infection, admission year and community vs hospital-onset. Abbreviations: CI, confidence interval; SOFA, sequential organ failure assessment.