Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study

Abstract

Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due to widespread over- and misuse of antimicrobials, there has been an alarming increase in global resistance, for which a standardized methodology for geographic surveillance would be highly beneficial. To demonstrate that a standardized methodology could be used to provide molecular surveillance of antimicrobial resistance (AMR) genes, we initiated a pilot study to test 130 diarrheal pathogens (<i>Campylobacter</i> spp., <i>Escherichia coli</i>, <i>Salmonella</i>, and <i>Shigella</i> spp.) from the USA, Peru, Egypt, Cambodia, and Kenya for the presence/absence of over 200 AMR determinants. We detected a total of 55 different determinants conferring resistance to ten different categories of antimicrobials: genes detected in ≥ 25 samples included <i>bla</i>_TEM, <i>tet</i>(A), <i>tet</i>(B), <i>mac</i>(A), <i>mac</i>(B), <i>aadA1/A2</i>, <i>strA</i>, <i>strB</i>, <i>sul1</i>, <i>sul2</i>, <i>qacE</i>Δ1, <i>cmr</i>, and <i>dfrA1</i>. The number of determinants per strain ranged from none (several <i>Campylobacter</i> spp. strains) to sixteen, with isolates from Egypt harboring a wider variety and greater number of genes per isolate than other sites. Two samples harbored carbapenemase genes, <i>bla</i>_OXA-48 or <i>bla</i>_NDM. Genes conferring resistance to azithromycin (<i>ere</i>(A), <i>mph</i>(A)/<i>mph</i>(K), <i>erm</i>(B)), a first-line therapeutic for severe diarrhea, were detected in over 10% of all Enterobacteriaceae tested: these included >25% of the Enterobacteriaceae from Egypt and Kenya. Forty-six percent of the Egyptian Enterobacteriaceae harbored genes encoding CTX-M-1 or CTX-M-9 families of extended-spectrum β-lactamases. Overall, the data provide cross-comparable resistome information to establish regional trends in support of international surveillance activities and potentially guide geospatially informed medical care.