Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US

Abstract

Importance: Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy.

Objective: To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality.

Design, setting, and participants: This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis.

Exposures: Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected.

Main outcomes and measures: Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species.

Results: Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]).

Conclusions and relevance: In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Figure 1.. Study Cohort Flowchart

CNS indicates coagulase-negative staphylococci; GNR, gram-negative rod; and GPC, gram-positive cocci.

Figure 2.. Number of Patients Infected With Pathogens and Proportions of Appropriate Empirical Antimicrobial Therapy by Pathogen

CRE indicates carbapenem-resistant Enterobacterales; CTX-RO, ceftriaxone-resistant gram-negative organism; E coli, Escherichia coli; ESBL, extended-spectrum β-lactamase–producing gram-negative organism; MRSA, methicillin-resistant Staphylococcus aureus; P aeruginosa, Pseudomonas aeruginosa; S aureus, Staphylococcus aureus; and VRE, vancomycin-resistant Enterococcus.

Figure 3.. Adjusted Odds of In-Hospital Death Associated With Appropriate Empirical Antimicrobial Therapy by Pathogen

CRE indicates carbapenem-resistant Enterobacterales; CTX-RO, ceftriaxone-resistant gram-negative organism; E coli, Escherichia coli; ESBL, extended-spectrum β-lactamase–producing gram-negative organism; MRSA, methicillin-resistant Staphylococcus aureus; OR, odds ratio; P aeruginosa, Pseudomonas aeruginosa; S aureus, Staphylococcus aureus; and VRE, vancomycin-resistant Enterococcus.