Clinical Epidemiology and Molecular Analysis of Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Nepal: Characteristics of Sequence Types 131 and 648

Abstract

f Recently, CTX-M-type extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli strains have emerged worldwide. In particular, E. coli with O antigen type 25 (O25) and sequence type 131 (ST131), which is often associated with the CTX-M-15 ESBL, has been increasingly reported globally; however, epidemiology reports on ESBL-producing E. coli in Asia are limited. Patients with clinical isolates of ESBL-producing E. coli in the Tribhuvan University teaching hospital in Kathmandu, Nepal, were included in this study. Whole-genome sequencing of the isolates was conducted to analyze multilocus sequence types, phylotypes, virulence genotypes, O25b-ST131 clones, and distribution of acquired drug resistance genes. During the study period, 105 patients with ESBL-producing E. coli isolation were identified, and the majority (90%) of these isolates were CTX-M-15 positive. The most dominant ST was ST131 (n ‫؍‬ 54; 51.4%), followed by ST648 (n ‫؍‬ 15; 14.3%). All ST131 isolates were identified as O25b-ST131 clones, subclone H30-Rx. Three ST groups (ST131, ST648, and non-ST131/648) were compared in further analyses. ST648 isolates had a proportionally higher resistance to non-␤-lactam antibiotics and featured drug-resistant genes more frequently than ST131 or non-ST131/648 isolates. ST131 possessed the most virulence genes, followed by ST648. The clinical characteristics were similar among groups. More than 38% of ESBL-producing E. coli isolates were from the outpatient clinic, and pregnant patients comprised 24% of ESBL-producing E. coli cases. We revealed that the high resistance of ESBL-producing E. coli to multiple classes of antibiotics in Nepal is driven mainly by CTX-M-producing ST131 and ST648. Their immense prevalence in the communities is a matter of great concern. E scherichia coli is a part of the normal human and animal gastrointestinal flora; it is the most common cause of urinary tract infections and also causes various other infectious conditions, such as intra-abdominal infections, neonatal meningitis, and septicemia (1-3).Recently, extended-spectrum-beta-lactamase (ESBL) producing E. coli strains, particularly strains producing CTX-M-type ESBLs, have emerged worldwide (4). In particular, E. coli with O antigen type 25 (O25) and sequence type 131 (ST131) is often associated with the CTX-M-15 ESBL and has been increasingly reported globally. These bacteria are resistant to classes of antibiotics distinct from ␤-lactams, such as fluoroquinolones and trimethoprim-sulfamethoxazole (5, 6). Epidemiology reports on ESBLproducing E. coli in Asia are limited to date. To the best of our knowledge, there has been no report on the prevalence of pandemic ESBL-producing E. coli ST131, or other potentially dominant ESBL-producing E. coli STs, or clinical and microbiological information pertaining to their isolation in Nepal. Nepal is located in south Asia and adjacent to India, where a high proportion of resistant Gram-negative bacteria has been reported (7); understanding the epidemiology of ESBL-producing E. coli in t...

Identification of IncA/C Plasmid Replication and Maintenance Genes and Development of a Plasmid Multilocus Sequence Typing Scheme

“…The complete genome of MS6198 was determined and shown to consist of a circular chromosome comprising 5,176,750 base pairs (51.59% G-C content). In silico typing assigned MS6198 to sequence type 648 (ST648), which has been associated with a number of disease outbreaks in Asia and Europe (33)(34)(35). MS6198 contained a number of UPEC virulence factors, including genes encoding type 1 fimbriae, Ag43, capsule, and several iron acquisition systems.…”

The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections

“…149 These same findings were later reported from a US site 76 and from Nepal as well. 150 These analyses suggest that misuse of antimicrobials, particularly in the community, plays an important role in the acquisition and spread of this clone. Other common mode of MDRO acquisition, that is, patient-to-patient transmission, probably plays a lesser role in the dissemination of this clone in the community.…”

Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131- H 30Rx and ST131- H 30R1 Strains

“…Whole-genome sequencing (WGS), an emerging tool for advanced molecular epidemiological investigations involving MDR organisms, allows identification of extended resistance and virulence genotypes and elucidation of transmission routes (7)(8)(9)(10)(11)(12)(13). Recently, WGS-based phylogenetic analyses of E. coli ST131 strains identified a CTX-M-15-associated sublineage, designated H30Rx, within ST131-H30R, which is the fluoroquinoloneresistant subset within ST131-H30 (11).…”