Evaluation of in vitro and in vivo antimicrobial activity of a new topical antiinfective agent.
ST 1103 (Undecyl [4-N,N,N-trimethylammonium-(R)-3- isovaleroyloxy]-butanoate methanesulfonate) is a novel compound endowed with a broad antimicrobial spectrum. ST 1103 is able to inhibit the in vitro growth of Gram-positive bacteria (mean MIC value of 2.60 micrograms/ml), Gram-negative bacteria (mean MIC value of 27.00 micrograms/ml), yeasts and yeast-like fungi (mean MIC value of 3.76 micrograms/ml), filamentous and dermatophytic fungi (mean MIC value of 18.33 micrograms/ml). Since indirect evidence indicates a poor oral absorbtion, ST 1103 was topically administered to mice with skin infections caused by mixed inocula. In these conditions, ST 1103 was able to cure mice infected with T. quinckeanum, S. aureus as well as immunodepressed mice infected with T. quinckeanum, S. aureus and C. albicans. Conversely, miconazole (reference compound) appeared inadequate, in our experimental conditions, for a definitive therapy of the skin mycosis superinfected by staphylococcus. By using an in vitro 3D-human skin model, ST 1103 was fairly well tolerated in terms of both cell viability and release of inflammatory mediators. In a dermal tolerance study in mice, ST 1103 at a concentration of 1% did not show any sign of local irritation on both intact and abraded skin after an 8-day topical treatment. In conclusion, ST 1103 appears to be a promising candidate for treatment of cutaneous infections caused by mixed microbial pathogens.
D'Urso
C M
CM
Department of Microbiology and Immunology, Sigma-Tau S.p.A., Pomezia, Italy.
Gramiccioli
G
G
Mirri
S
S
Foresta
P
P
Arrigoni Martelli
E
E
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008698:Mesylates / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D012867:Skin / Q000187:drug effects; D012874:Skin Diseases, Infectious / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D008698:Mesylates; C095920:ST 1103