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Updated: May 17, 2026

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole?
Asha C Bowen1, Rachael A Lilliebridge, Steven Y C Tong
1Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia. asha.bowen@menzies.edu.au
Abstract:
Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes' in vitro susceptibility to SXT depends on the medium's thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ≤ 1 mg/liter) and resistance (MIC, >2 mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing.
Insights
Trimethoprim-sulfamethoxazole (SXT) susceptibility in Streptococcus pyogenes is confirmed on regulated media, challenging prior beliefs of resistance. This finding supports SXT use for skin and soft tissue infections (SSTIs).
Area of Science:
- Microbiology
- Antimicrobial Susceptibility Testing
- Clinical Infectious Diseases
Background:
- Streptococcus pyogenes is often considered resistant to trimethoprim-sulfamethoxazole (SXT).
- This perceived resistance is linked to thymidine content in culture media, affecting folate metabolism inhibition.
- Standardized Mueller-Hinton agar (MHA) now has regulated thymidine concentrations.
Purpose of the Study:
- To investigate Streptococcus pyogenes susceptibility to SXT across various standardized media.
- To re-evaluate the in vitro efficacy of SXT against S. pyogenes.
- To provide evidence supporting or refuting SXT use in skin and soft tissue infections (SSTIs).
Main Methods:
- Two sets of 100 clinical S. pyogenes isolates were tested.
- Susceptibility was determined using SXT Etests on MHA with defibrinated horse blood and β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA).
- European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints were used for interpretation.
Main Results:
- In study 1, 99% of isolates were susceptible to SXT on MHA, MHBA, and MHLHBA (geometric mean MICs: 0.04–0.05 mg/liter).
- In study 2, 100% of isolates were susceptible on MHF, MHS, MHA, and MHLHBA (geometric mean MICs: 0.07–0.16 mg/liter).
- All tested media demonstrated high in vitro susceptibility of S. pyogenes to SXT.
Conclusions:
- This study confirms the in vitro susceptibility of Streptococcus pyogenes to trimethoprim-sulfamethoxazole.
- The findings challenge the long-held belief of SXT resistance in S. pyogenes.
- Results support the potential clinical use of SXT for skin and soft tissue infections caused by S. pyogenes.
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