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

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.

• Authors: Julian G Hurdle, Alex J O'Neill, Ian Chopra
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 54 Issue 2 Pg. 549-52 (Aug 2004) ISSN: 0305-7453 [Print] England
• PMID: 15243028 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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