Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

Abstract

Heidi Syre (HS), Marit Andrea Klokkhammer Hetland (MAKH), Eva Bernhoff (EB), Marianne Bollestad (MB), Nils Grude (NG), Gunnar Skov Simonsen (GSS), Iren Høyland Löhr (IHL). Microbial risk factors for treatment failure of pivmecillinam in community-acquired urinary tract infections caused by ESBL-producing Escherichia coliObjectives: The aim of this study was to identify microbial phenotypic and/or molecular risk factors for treatment failure of pivmecillinam in community acquired urinary tract infections (ca-UTIs) caused by ESBL-producing E. coli.Methods: Eighty-nine ESBL-producing E. coli isolated from women suffering from ca-UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip.Whole genome sequencing was performed on a Miseq platform and genome assembly was performed using SPAdes v3.11.0.Results: Neither mecillinam MICs nor ESBL-genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with E. coli ST131 were more likely to experience treatment failure compared to patients infected with non-ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with E. coli ST69 were more often successfully treated compared to patients infected with non-ST69 (p 0.04). Patients infected with blaCTX-M-15 ST131 strains were more likely to experience treatment failure than those infected with non-blaCTX-M-15 ST131 strains (p 0.02).Conclusions: The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results.

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages

“…Bacterial genomes of the CC131 dataset. Assemblies from CC131 isolates of the main dataset were analyzed in the context of publicly available CC131 wholegenome sequences including assemblies of 92 isolates from children with febrile UTI 73 defined here as invasive UPEC isolates, 10 urosepsis isolates 17 , 16 cystitis isolates 74 , 52 isolates of various clinical phenotypes 46 , and 799 isolates without available metadata randomly downloaded from Enterobase 75 . Forty-eight complete or near-complete genomes of CC131 isolates identified on NCBI were also included in the analysis.…”

Prevalence of extended spectrum beta-lactamase (ESBL) Escherichia coli recovered from ICU and non-ICU at dr. Zainoel Abidin General Hospital

“…This underscores the significance of ESBL E. coli as the primary causative agent in urinary tract infections (UTIs). Multiple studies have established the association of ESBL E. coli with both community-and hospital-acquired UTIs [17][18][19]. In community settings, ESBL-producing E. coli has emerged as a notable etiological factor for UTIs [19].…”

“…Multiple studies have established the association of ESBL E. coli with both community-and hospital-acquired UTIs [17][18][19]. In community settings, ESBL-producing E. coli has emerged as a notable etiological factor for UTIs [19]. A study conducted in China revealed a high prevalence of ESBL-producing E. coli among adults afflicted with community-acquired UTIs [17].…”