Diverse genetic lineages spreading across healthcare and community boundaries underlie extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) colonization burden in Botswana.

Abstract

Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are a global health challenge, molecular data from low- and middle-income countries are limited. We employed whole-genome sequencing to characterize ESCrE in community and healthcare settings in Botswana. Study isolates were collected from three hospitals and six outpatient clinics in Botswana, as well as from adults and children in the community. Enrollment occurred from 1/15/2020 to 9/4/2020, but paused from 4/2/2020 to 5/21/2020 due to a countrywide COVID-19 lockdown. Isolates from rectal swabs of participants testing positive for ESCrE underwent whole-genome sequencing. Genomic data were analyzed to characterize resistance genes, sequence types (STs), and exposures associated with putative inter-person transmission. Escherichia coli and Klebsiella pneumoniae ESCrE were diverse, represented by 87 and 49 STs respectively, carrying 16 different ESBL gene alleles. Twelve E. coli STs accounted for most isolates, with these common STs being observed in both community and healthcare settings, and increasing in the proportion post-lockdown (61% versus 80%). Examination of factors associated with harboring genetically similar E. coli revealed shared household and social networks across lockdown periods, with differences in shared hospital exposure and participant age between lockdown periods. Genomic characterization of ESCrE in Botswana revealed diverse STs carrying common ESBL genes, with overlapping STs among hospital and community participants consistent with intersecting transmission networks. Risk analysis of transmission supported the role of direct human contact, with the COVID-19 lockdown impacting the diversity of ESCrE and transmission pathways, highlighting the potential for behavioral changes to impact ESCrE spread.