Heterogeneity of antimicrobial susceptibility testing results for sulfamethoxazole/trimethoprim obtained from clinical equine Staphylococcus aureus isolates using different methods

Vet Microbiol. 2020 Mar:242:108600. doi: 10.1016/j.vetmic.2020.108600. Epub 2020 Feb 1.

Abstract

Based on antimicrobial susceptibility testing (AST), correct classifications as susceptible, intermediate or resistant are challenging for some antimicrobial agent-bacterial species combinations. In this study, we investigated 19 equine Staphylococcus aureus isolates for their susceptibility to the combination sulfamethoxazole/trimethoprim (SXT) by using broth microdilution (BMD), agar disk diffusion (DD) and automated test systems. To elucidate the presence of the corresponding genetic resistance properties among the isolates, whole genome sequence analysis was performed and the genomes were screened for trimethoprim (TMP) resistance genes and mutations in the deduced FolP amino acid (aa) sequences, known to confer sulfonamide resistance. To check for hetero-resistance, zone diameters in DD were screened after 18 and 42 h of incubation. All 19 isolates harboured one of the TMP resistance genes dfrG or dfrS1. Three isolates had an aa exchange in their FolP aa sequence (F17L), which has previously been described to result in sulfonamide resistance. These isolates were classified as SXT-resistant by all methods. The remaining 16 isolates were classified as SXT-susceptible or -intermediate (BMD and/or DD) or SXT-resistant (mainly automated test systems). None of the isolates had relevant aa variations in their FolP aa sequences. All 19 isolates showed slight growth within their SXT inhibition zone by DD, pointing towards hetero-resistance. Overall, automated test systems classified isolates lacking genetic resistance determinants more frequently as SXT-resistant than DD and BMD. Therefore, further studies are needed to define a reliable method for SXT susceptibility testing.

Keywords: Antimicrobial resistance; Diagnostics; Hetero-resistance; VITEK.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Drug Resistance, Bacterial / genetics*
  • Horses / microbiology
  • Microbial Sensitivity Tests
  • Mutation
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / veterinary*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics*
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology*
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Trimethoprim, Sulfamethoxazole Drug Combination