The Risk of Emerging Resistance to Trimethoprim/Sulfamethoxazole in Staphylococcus aureus

Takumi Sato1, Ryota Ito1, Masato Kawamura1

  • 1Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

Abstract

Insights

The study found that prolonged exposure to trimethoprim/sulfamethoxazole (SXT) increases the risk of developing SXT-resistant Staphylococcus aureus strains. This emergence of resistant bacteria highlights the need for careful antibiotic use.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • The increasing prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) drives global demand for trimethoprim/sulfamethoxazole (SXT).
  • The potential for SXT overuse to drive the emergence of resistant strains remains unclear.

Purpose of the Study:

  • To investigate the risk of trimethoprim/sulfamethoxazole (SXT)-resistant Staphylococcus aureus mutant emergence through in vitro SXT exposure.
  • To analyze the genetic mutations associated with SXT resistance in Staphylococcus aureus.

Main Methods:

  • Exposure of 40 clinical Staphylococcus aureus isolates (20 MSSA, 20 MRSA) to sub-inhibitory concentrations of SXT daily.
  • Daily determination of SXT Minimum Inhibitory Concentration (MIC) and dfrB DNA sequencing to identify resistance mutations.

Main Results:

  • SXT-resistant strains emerged by day 8 and reached 45% prevalence (18/40 isolates) after 14 days of exposure.
  • Half of the resistant strains exhibited the F98Y mutation in the dfrB gene, conferring SXT resistance even without ongoing selective pressure.

Conclusions:

  • Prolonged SXT exposure, specifically 14 days or more, significantly increases the risk of SXT-resistant Staphylococcus aureus emergence.
  • The identified dfrB mutation suggests a mechanism for sustained resistance development in Staphylococcus aureus.

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