Abstract:
The World Health Organization (WHO) has declared antimicrobial resistance
(AMR) as one of the top 10 global public health threats facing humanity. The
aims of this study were to report currently Scarce data on AMR mechanism: β
lactamase production, in uropathogenic Enterobacteriales in Sri Lanka and to
identify bench tests to detect β-lactamase production in low-income settings. A
total of 422 Enterobacterales uropathogens from community-acquired urinary
tract infections (CA-UTI) and hospital acquired UTI (HA-UTI) were studied. β
lactamase types: Extended spectrum β-lactamase (ESBL), AmpC β-lactamase
and carbapenemase production and the bla genes that encodes them, identified by
phenotypic tests followed by PCR and Sanger sequencing. Nine isolates were
further analysed by whole genome sequencing. Common uropathogens identified
were Escherichia coli, Klebsiella pneumoniae and Enterobacter sp. The
prevalence of ESBL (50%), AmpC β-lactamase (19%) and carbapenemase (11%)
was high and was greater in HA-UTI (75%) than CA-UTI (42%). The related
genes: blaTEM-1, blaSHV-1, blaSHV-2, blaSHV-11, blaSHV-28 and blaOXA-1; blaCTX-M-15,
blaCMY-42, blaCMY- 2, blaDHA-1, blaACT-1, blaACT-7, blaNDM-1, blaNDM-4, blaOXA-181 and
blaOXA-232 were identified. BlaACT-7 and blaOXA-232 were novel genes to the country.
Co-occurrence of multiple bla genes (25%) was a concerning phenomena. Omp
mutations leading to carbapenem resistance even without producing
carbapenemase enzymes were detected. K. pneumoniae ST16, and E.hormaechei
subsp. Steigerwalt ST93 were described for the first time in the country.
Virulence genes associated with AMR genes and mobile genetic elements were
identified that lead to spread of more pathogenic antimicrobial resistant strains.
Screening with cefotaxime or ceftriaxone, cefoxitin and meropenem, followed by
the modified double disc synergy test, AmpC disc test and the modified
carbapenem inhibition method were identified as suitable bench tests to detect β
lactamase production in Enterobacterales in the local setting. The findings of this
study will contribute to the local and global strategies in controling AMR
dissemination.
