Dehydroepiandosterone induction of increased resistance to vancomycin in Staphylococcus aureus clinical isolates (MSSA, MRSA)

AIMS: To investigate whether dehydroepiandosterone (DHEA), an androgen present throughout life, alters the response of Staphylococcus aureus clinical isolates to vancomycin. METHODS AND RESULTS: DHEA in physiologically relevant concentrations (0.1, 0.5, 1.0 and 5.0 micromol l(-1)) was tested for its effect on methicillin-sensitive S. aureus (MSSA, n = 53) and methicillin-resistant S. aureus (MRSA, n = 73) response to vancomycin using standard protocols. Mutant selection was determined by serial transfer of selected isolates (n = 5). DHEA-mediated at least a fourfold increase in vancomycin MIC for 42% of MSSA and 21% of MRSA. For five of the isolates (0.1 and 0.5 micromol l(-1) DHEA) the MIC was increased to levels (8 microg ml(-1)) defined as vancomycin-intermediate resistance. CONCLUSION: Resistance was detected only in the presence of DHEA, and was not related to altered generation time, indicating induction of phenotypic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings require further investigation to determine what role DHEA plays in clinical vancomycin treatment failure that has been reported in the absence of vancomycin genotypic resistance or heteroresistance.