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JAC Advance Access originally published online on July 8, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(2):549-552; doi:10.1093/jac/dkh352
JAC vol.54 no.2 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

Anti-staphylococcal activity of indolmycin, a potential topical agent for control of staphylococcal infections

Julian G. Hurdle, Alex J. O'Neill and Ian Chopra*

Antimicrobial Research Centre and School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK

* Corresponding author. Tel: +44-113-343-5604; Fax: +44-113-343-3167; Email: i.chopra{at}leeds.ac.uk

Objectives: We sought to investigate the anti-staphylococcal activity of indolmycin, with particular emphasis on comparing its activity with fusidic acid and mupirocin.

Methods: Established procedures were used to examine the activity of indolmycin against a range of clinical isolates, including strains resistant to fusidic acid and mupirocin. Indolmycin-resistant mutants were recovered and characterized phenotypically and genotypically.

Results: Indolmycin was bacteriostatic and demonstrated good activity against MSSA (methicillin-susceptible Staphylococcus aureus), MRSA (methicillin-resistant S. aureus) and VISA (vancomycin-intermediate S. aureus), including strains resistant to mupirocin or fusidic acid. Spontaneous indolmycin-resistant mutants occurred at a lower frequency than those selected by mupirocin or fusidic acid and exhibited no cross-resistance with the comparative drugs. High-level resistance (indolmycin MIC 128 mg/L) that was associated with an H43N mutation in tryptophanyl-tRNA synthetase (TrpS), the target enzyme of indolmycin, resulted in loss of bacterial fitness. However, the locus responsible for low-level indolmycin resistance (indolmycin MICs 8–32 mg/L) was not identified.

Conclusions: Indolmycin is a potent anti-staphylococcal agent, which exhibits activity against mupirocin- and fusidic acid-resistant strains. Indolmycin might be a candidate for development as a topical agent in the treatment of staphylococcal infections and nasal carriage of MRSA.

Keywords: Staphylococcus aureus , antibiotics , dermatological infections , control of MRSA carriage


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