Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it

Abstract

Background Escherichia coli bloodstream infections (BSIs) account for high mortality rates (5%–30%). Determinants of death are unclear, especially since the emergence of ESBL producers. Objectives To determine the relative weight of host characteristics, bacterial virulence and antibiotic resistance in the outcome of patients suffering from E. coli BSI. Methods All consecutive patients suffering from E. coli BSI in seven teaching hospitals around Paris were prospectively included for 10 months. E. coli isolates were sequenced using Illumina NextSeq technology to determine the phylogroup, ST/ST complex (STc), virulence and antimicrobial resistance gene content. Risk factors associated with death at discharge or Day 28 were determined. Results Overall, 545 patients (mean ± SD age 68.5 ± 16.5 years; 52.5% male) were included. Mean Charlson comorbidity index (CCI) was 5.6 (± 3.1); 19.6% and 12.8% presented with sepsis and septic shock, respectively. Portals of entry were mainly urinary (51.9%), digestive (41.9%) and pulmonary (3.5%); 98/545 isolates (18%) were third-generation cephalosporin resistant (3GC-R), including 86 ESBL producers. In-hospital death (or at Day 28) was 52/545 (9.5%). Factors independently associated with death were a pulmonary portal of entry [adjusted OR (aOR) 6.54, 95% CI 2.23–19.2, P = 0.0006], the iha_17 virulence gene (aOR 4.41, 95% CI 1.23–15.74, P = 0.022), the STc88 (aOR 3.62, 95% CI 1.30–10.09, P = 0.014), healthcare-associated infections (aOR 1.98, 95% CI 1.04–3.76, P = 0.036) and high CCI (aOR 1.14, 95% CI 1.04–1.26, P = 0.006), but not ESBL/3GC-R. Conclusions Host factors, portal of entry and bacterial characteristics remain major determinants associated with mortality in E. coli BSIs. Despite a high prevalence of ESBL producers, antibiotic resistance did not impact mortality. (ClinicalTrials.gov identifier: NCT02890901.)

Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study

“…The full list of the 370 strains used in the association analysis, together with their main characteristics is reported in S1 Table . These strains belong to various published collections: ECOR (N = 71) [ 31 ], IAI (n = 81) [ 14 ], NILS (N = 82) [ 33 ], Septicoli (N = 39) [ 10 ], ROAR (N = 30) [ 34 ], Guyana (N = 12) [ 32 ], Coliville (N = 8) [ 35 ], FN (N = 6) [ 36 ], COLIRED (N = 3) [ 37 ], COLIBAFI (N = 2) [ 7 ], correspond to archetypal strains (N = 7) or are miscellaneous strains from our personal collections (N = 29). The isolation host is predominantly humans (N = 291), followed by animals (N = 72) and some strains were isolated from the environment (N = 6).…”

“…The latter taxa are rarely isolated in humans but are more frequently found in the environment and avian species where they can cause intestinal infections [3][4][5]. In humans, extra-intestinal infections represent a considerable burden [6], with bloodstream infections (bacteraemia) being the most severe with a high attributable mortality of between 10-30% [7][8][9][10]. The regular increase over the last 20 years of E. coli bloodstream incidence [11] and antibiotic resistance [12] is particularly worrisome.…”

The population genomics of increased virulence and antibiotic resistance in human commensal Escherichia coli over 30 years in France

“…After DNA extraction, whole-genome of each strain was sequenced using Illumina NextSeq 2×150 bp after NextEra XT library preparation (Illumina, San Diego, CA) as in de Lastours et al (de Lastours et al 2020).…”

“…Although the gut is the typical habitat of E. coli and likely the main ecological context of selection for virulence and resistance, most studies on the evolution of virulence and antibiotic resistance focused on pathogenic clinical strains isolated from extra-intestinal infections (de Lastours et al 2020; Cole et al 2019; Kallonen et al 2017; Salipante et al 2015). Extra-intestinal infections are a rare occurrence in E. coli ’s life: the incidence of urinary tract infections is of the order of 10 −2 per person-year (Foxman 2010), and of bacteremia of the order of 10 −4 per person-year (Goto et al 2017).…”

“…Extra-intestinal infections are a rare occurrence in E. coli ’s life: the incidence of urinary tract infections is of the order of 10 −2 per person-year (Foxman 2010), and of bacteremia of the order of 10 −4 per person-year (Goto et al 2017). In comparison to commensal E. coli , E. coli sampled from infections are biased towards strains carrying more virulent genes (Clermont et al 2017; de Lastours et al 2020; Kallonen et al 2017). Strains from infections may also be less diverse than commensal strains as they belong to some specific clones (Denamur et al 2021; Kauffmann 1947), hindering the detection of temporal trends in these elements and the evolutionary mechanisms driving the emergence of pathogenic clones (Arimizu et al 2019).…”