Anti-staphylococcal activity of indolmycin, a potential topical agent for control of staphylococcal infections.
OBJECTIVE
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.
Hurdle
Julian G
JG
Antimicrobial Research Centre and School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK.
O'Neill
Alex J
AJ
Chopra
Ian
I
D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005672:Fusidic Acid / Q000494:pharmacology; D001411:Geobacillus stearothermophilus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D007211:Indoles / Q000494:pharmacology*; D016712:Mupirocin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D014369:Tryptophan-tRNA Ligase / Q000378:metabolism
D000891:Anti-Infective Agents, Local; D007211:Indoles; D005672:Fusidic Acid; D016712:Mupirocin; D014369:Tryptophan-tRNA Ligase; C001447:indolmycin