Antibiotic-resistant E. coli poses growing threat to hospitals across Nordic region

<p>Antimicrobial resistance (AMR), which has been increasing globally over the past half-century, is a major global health issue. The most common pathogen causing bacteremia with broad-spectrum antibiotic resistance is Escherichia coli.</p><p>This thesis investigated AMR, with a particular focus on extended-spectrum β-lactamase-producing E. coli (ESBL-Ec), from epidemiological, clinical, and microbiological perspectives.</p><p>Study I retrospectively examined antibiotic consumption, empirical hospital treatment guidelines, and antibiotic resistance among major pathogens in the Nordic countries from 2010 to 2018. Resistance rates were similar at the end of the study period, with ESBL-Ec rates ranging from 6.8% to 8.3%. Despite this, treatment guidelines diverged regarding pyelonephritis and sepsis. Rates of methicillin-resistant Staphylococcus aureus were low across all Nordic countries.</p><p>Study II retrospectively investigated all patients with ESBL-Ec isolated from blood and urine between 2009 and 2018 in the Region of Östergötland, Sweden. 76 patients with 77 episodes of infection with ESBL-Ec were matched 1:1 by age and gender with patients infected with non-ESBL E. coli. The globally spread E. coli Sequence Type 131 accounted for 55% of all ESBL-Ec isolates. Risk factors associated with ESBL-Ec infection included a previous genitourinary procedure (RR 4.66, p=0.005) and a history of ESBL-Ec in prior cultures (RR 12.14, p=0.024). Despite a significant difference in time to appropriate antibiotic therapy (27:15 h vs. 02:14 h, p&lt;0.001), no difference in 30-day mortality was observed (6% vs. 6%, p&gt;0.999).</p><p>Study III investigated virulence factors and sepsis among patients infected with ESBL-Ec in Study II, with particular focus on the clade ST131 and its subclade H30Rx. Using whole-genome sequencing data, all ESBL-Ec isolates were classified into three groups: ST131 H30Rx, ST131 Other, and non-ST131. Several virulence factors were significantly more common among ST131 isolates and, in the case of enterobactin production and increased serum survival, specifically among ST131 H30Rx isolates. These virulence factors have previously been primarily associated with recurrence. In addition, sepsis within 36 hours of hospital admission was less common among patients with infections caused by ST131 H30Rx.</p><p>Study IV was a prospective cohort study investigating ESBL-Ec gut carriage among patients with urinary tract infection (UTI) caused by ESBL-Ec in the Region of Östergötland, Sweden. Of 49 participants, 41% were long-term carriers and 35% were short-term carriers, while the remainder were classified as heterogeneous carriers and excluded from statistical comparison. ST131 was more common among long-term carriers (p=0.028). Corynebacterium epidermidicanis was associated with long-term carriage in gut microbiome analysis.</p><p>In conclusion, the increase in ESBL-Ec rates globally, including in Sweden, represents a complex problem. In Study II and IV, the globally successful clade ST131 was not associated with sepsis but rather with prolonged gut carriage. In addition, in Study III, several virulence factors associated with recurrent infection were significantly more common among ST131 isolates.</p>