Details

Autor(en) / Beteiligte

• Nurjadi, Dennis
• Chanthalangsy, Quan
• Zizmann, Elfi
• Stuermer, Vanessa
• Moll, Maximilian
• Klein, Sabrina
• Boutin, Sébastien
• Heeg, Klaus
• Zanger, Philipp
• Zhang, Kunyan

Titel

Phenotypic Detection of Hemin-Inducible Trimethoprim-Sulfamethoxazole Heteroresistance in Staphylococcus aureus

Ist Teil von

• Microbiology spectrum, 2021-10, Vol.9 (2), p.e0151021-e0151021

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Trimethoprim-sulfamethoxazole (SXT) is a valuable second-line antimicrobial agent to treat methicillin-resistant Staphylococcus aureus infections. Discrepancies between various antibiotic susceptibility testing (AST) methods for SXT susceptibility in S. aureus have been described. Here, we describe a hemin-inducible heteroresistance phenotype in S. aureus. We compared the results of the Vitek 2 AST on a set of 95 S. aureus clinical isolates with broth microdilution, disk diffusion using standard Mueller-Hinton agar, and disk diffusion using Mueller-Hinton agar supplemented with 5% horse blood (MHF). To investigate the potential clinical relevance of SXT heteroresistance, an Galleria mellonella infection assay was performed. All Vitek 2 SXT-susceptible (  = 17) isolates were concordant with AST results by other methods applied in this study. In 32/78 (41%) of Vitek 2 SXT-resistant isolates, we observed a heteroresistant growth phenotype on MHF. The heteroresistance phenotype was associated with the presence of genes, encoding trimethoprim resistance. The addition of a hemin-impregnated disk in a double disk diffusion method on standard Mueller-Hinton agar was able to induce growth in the SXT zone of inhibition. An infection assay with G. mellonella suggested that the SXT heteroresistance phenotype resulted in lethality similar to that of the SXT-resistant phenotype. In this study, we describe a novel hemin-inducible heteroresistance phenotype in S. aureus. This heteroresistance phenotype may be missed by standard AST methods but can be detected by performing disk diffusion using Mueller-Hinton agar supplemented with 5% horse blood, commonly used for AST of fastidious organisms. This phenomenon may partly explain the discrepancies of AST methods in determining SXT resistance in S. aureus. Staphylococcus aureus is one of most important pathogens in clinical medicine. Besides its virulence, the acquisition or emergence of resistance toward antibiotic agents, in particular to beta-lactam antibiotics (methicillin-resistant S. aureus [MRSA]), poses a major therapeutic challenge. Trimethoprim-sulfamethoxazole (SXT) is one of the effective antimicrobial agents of last resort to treat MRSA infections. Here, we report the detection of a SXT-heteroresistant phenotype which is inducible by hemin and can be detected using Mueller-Hinton agar supplemented with horse blood. Heteroresistance describes the presence or emergence of resistant subpopulations, which may potentially lead to inaccurate antibiotic susceptibility testing results and influence the success of antibiotic therapy.