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

J Antimicrob Chemother. 2004 Aug;54(2):549-52. doi: 10.1093/jac/dkh352. Epub 2004 Jul 8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents, Local / pharmacology*
  • Drug Resistance, Bacterial
  • Fusidic Acid / pharmacology
  • Geobacillus stearothermophilus / drug effects
  • Geobacillus stearothermophilus / enzymology
  • Geobacillus stearothermophilus / genetics
  • Indoles / pharmacology*
  • Mupirocin / pharmacology
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics
  • Tryptophan-tRNA Ligase / metabolism

Substances

  • Anti-Infective Agents, Local
  • Indoles
  • Fusidic Acid
  • Mupirocin
  • Tryptophan-tRNA Ligase
  • indolmycin