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

Julian G Hurdle1, Alex J O'Neill, Ian Chopra

  • 1Antimicrobial Research Centre and School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK.

The Journal of Antimicrobial Chemotherapy
|July 10, 2004
PubMed
Abstract

Insights

Indolmycin shows potent anti-staphylococcal activity, even against resistant strains. This antibiotic may be a promising topical treatment for Staphylococcus aureus infections and nasal carriage.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Staphylococcus aureus (S. aureus) infections pose a significant public health challenge.
  • Emergence of resistance to current antibiotics like fusidic acid and mupirocin necessitates novel therapeutic agents.
  • Indolmycin is an antibiotic with a known mechanism of action against S. aureus.

Purpose of the Study:

  • To evaluate the anti-staphylococcal activity of indolmycin.
  • To compare indolmycin's efficacy against fusidic acid and mupirocin.
  • To investigate indolmycin resistance mechanisms.

Main Methods:

  • Assessed indolmycin activity against clinical S. aureus isolates, including resistant strains.
  • Generated and characterized indolmycin-resistant mutants.
  • Determined minimum inhibitory concentrations (MICs) and analyzed mutations in tryptophanyl-tRNA synthetase (TrpS).

Main Results:

  • Indolmycin demonstrated bacteriostatic activity against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA).
  • Effective against strains resistant to mupirocin and fusidic acid, with lower spontaneous resistance mutation frequency compared to comparators.
  • High-level resistance linked to an H43N mutation in TrpS, leading to reduced bacterial fitness; low-level resistance locus unidentified.

Conclusions:

  • Indolmycin is a potent anti-staphylococcal agent effective against resistant strains.
  • Indolmycin exhibits promising activity against mupirocin- and fusidic acid-resistant S. aureus.
  • Indolmycin is a potential candidate for topical treatment of staphylococcal infections and MRSA nasal carriage.

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