Antibiotic Resistance Not Found to Contribute to Mortality Associated With E coli Bloodstream Infection

Antibiotic resistance was not found to have an impact on mortality in patients with bloodstream infections (BSIs) caused by Escherichia coli, according to the results of a study recently published in the Journal of Antimicrobial Chemotherapy.

E coli contributes significantly to hospital-acquired BSIs, as well as BSIs in the community, and the incidence of these infections has increased over the last decade. There has also been an increase in antibiotic resistance in healthcare and community settings worldwide as a result of the emergence of multidrug-resistant strains of E coli producing extended-spectrum β-lactamase (ESBL). In terms of death and disability-adjusted life-years, ESBL and/or third-generation cephalosporin-resistant (3GC-R) E coli represent the highest burden when compared with other multidrug-resistant organisms in Europe, with in-hospital mortality ranging from 5% to 30%. Using risk factors to determine which patients may be at high risk of dying from E coli BSIs is therefore crucial in clinical practice. However, since the emergence of ESBL producers, determinants of death in E coli BSIs remain unclear. Therefore, the SEPTICOLI (Prognostic Factors of Escherichia coli Bloodstream Infections: Severity Score and Therapeutic Implications; ClinicalTrials.gov identifier: NCT02890901) study was conducted to determine the relative weight of host characteristics, bacterial virulence, and antibiotic resistance in the outcome of patients with E coli BSI.

The study comprised 545 consecutive patients with E coli BSI (as determined by the isolation of E coli from at least 1 blood culture) in 7 teaching hospitals around Paris, France. Blood samples were obtained at the first visit, and E coli isolates were sequenced to determine virulence and antimicrobial resistance gene content, phylogroup, and strain type complex (STc). The primary end point was vital status at discharge or day 28.

Results suggest that although host factors, portal of entry, and bacterial characteristics were found to be major determinants associated with mortality in E coli BSIs, antibiotic resistance was not. The mean Charlson comorbidity index (CCI), which calculates burden of disease and mortality risk, was 5.6 (±3.1); 19.6% of patients presented with sepsis, and 12.8% of patients presented with septic shock. In total, 18% of isolates were 3GC-R, including 86 EBSL producers. The most common portal of entry was urinary (51.9%), followed by digestive (41.9%) and pulmonary (3.5%). Approximately 10% of patients died either in the hospital or at day 28. Factors found to be independently associated with death included pulmonary portal of entry (adjusted odds ratio [OR] 6.54; 95% CI, 2.23-19.2; P =.0006), the iha_17 virulence gene (aOR 4.41; 95% CI, 1.23-15.74; P =.022), STc88 (aOR 3.62; 95% CI, 1.30-10.09; P =.014), healthcare-associated infections (aOR 1.98; 95% CI, 1.04-3.76; P =.036), and high CCI (aOR 1.14; 95% CI, 1.04-1.26; P =.006). ESBL/3GC-R was not found to be independently associated with death, even after exclusion of patients with a urinary portal of entry who were more likely to have ESBL/3GC-R infections. Furthermore, there was no association of ESBL/3GC-R and mortality among the most severely affected patients (suffering sepsis or shock) for whom the death rate was 23%.

Overall, the study authors conclude that, “Interestingly, we found that 3GC resistance was not associated with higher mortality, even though patients received adequate antibiotic therapy later, because of either the cost of resistance or a possible conserved activity of antibiotics in vivo.”

Antibiotic Resistance Not Found to Contribute to Mortality Associated With E coli Bloodstream Infection

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