Faecal carriage of third-generation cephalosporin and carbapenem-resistant Escherichia coli and Klebsiella spp. in hospitalized patients and people in the community in Thailand

Background: Third generation cephalosporin (3GC) and/or carbapenem-resistant Escherichia coli and Klebsiella spp. are commonly excreted by people in Thailand. However, there is limited understanding of the molecular ecology of these bacteria and risk factors for their excretion by people in the Greater Mekong region. Our aim was to enhance this understanding by considering hospitalised and community-based volunteers in central Thailand. Methods: 3GC-resistant isolates (n=552) from rectal swabs provided by volunteers (n=591) were characterized using PCR, disc susceptibility testing, and for carbapenem-resistant isolates (n=27), by Illumina whole genome sequencing. Bayesian regularisation modelled associations between rectal swab-positivity and variables derived from volunteer-completed surveys and antimicrobial dispensing data. Results: Approximately 57% and 20% of rectal swabs were positive for 3GC-resistant E. coli or Klebsiella spp., respectively. Carbapenem resistance was seen in 10% and 1% of swabs from hospitalised and community volunteers, respectively. For hospitalised volunteers, 49/90 received at least one antibiotic between admission and providing a rectal swab. Ceftriaxone (a 3GC) use was common in our study hospital and in almost 50% of cases, dispensing was without reference to a specific clinical syndrome. 33/90 hospitalized volunteers received ceftriaxone, which was strongly associated with 3GC-resistant E. coli positivity. For community volunteers (n=501), associated risk factors for 3GC-resistant E. coli positivity were: working with poultry and purchasing food from fixed markets. 3GC-R was mechanistically diverse, but generally caused by group 1 CTX-Ms. Gentamicin resistance was common among 3GC-resistant isolates, with amikacin, colistin and carbapenem resistance being rare. Of 21 unique carbapenem-resistant isolates sequenced, a wide variety of sequence types were identified with no evidence of recent transmission. NDM-5 was the mechanism in E. coli and NDM-1 or OXA-232 in Klebsiella spp. Conclusions: We identified ceftriaxone therapy as a potential focus for stewardship approaches designed to reduce the selection for 3GC-resistant Enterobacterales in Thai community hospitals, which could also impact people in the community. However, factors such as food source and interaction with animals were also associated in the community population, which further implicates the potential for farmed animal sources of resistant bacteria (and therefore antibiotic usage practices on farms) in Thailand and the wider region.