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

Int J Mol Sci. 2020 Aug 18;21(16):5928. doi: 10.3390/ijms21165928.

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 (Campylobacter spp., Escherichia coli, Salmonella, and Shigella 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 blaTEM, tet(A), tet(B), mac(A), mac(B), aadA1/A2, strA, strB, sul1, sul2, qacEΔ1, cmr, and dfrA1. The number of determinants per strain ranged from none (several Campylobacter 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, blaOXA-48 or blaNDM. Genes conferring resistance to azithromycin (ere(A), mph(A)/mph(K), erm(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.

Keywords: Campylobacter; Escherichia coli; Salmonella; Shigella; antimicrobial resistance; diarrheal pathogen; microarray.

MeSH terms

  • Anti-Bacterial Agents / toxicity
  • Campylobacter / drug effects
  • Campylobacter / genetics*
  • Campylobacter / isolation & purification
  • Campylobacter / pathogenicity
  • Diarrhea / epidemiology
  • Diarrhea / microbiology*
  • Drug Resistance, Microbial*
  • Enteropathogenic Escherichia coli / drug effects
  • Enteropathogenic Escherichia coli / genetics*
  • Enteropathogenic Escherichia coli / isolation & purification
  • Enteropathogenic Escherichia coli / pathogenicity
  • Genes, Bacterial*
  • Humans
  • Salmonella / drug effects
  • Salmonella / genetics*
  • Salmonella / isolation & purification
  • Salmonella / pathogenicity
  • Shigella / drug effects
  • Shigella / genetics*
  • Shigella / isolation & purification
  • Shigella / pathogenicity

Substances

  • Anti-Bacterial Agents