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Titolo:
Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment of histoplasmosis in a murine model
Autore:
Goldberg, J; Connolly, P; Schnizlein-Bick, C; Durkin, M; Kohler, S; Smedema, M; Brizendine, E; Hector, R; Wheat, J;
Indirizzi:
Histoplasmosis Reference Lab, Indianapolis, IN 46202 USA Histoplasmosis Reference Lab Indianapolis IN USA 46202 olis, IN 46202 USA Dept Vet Affairs Hosp, Indianapolis, IN USA Dept Vet Affairs Hosp Indianapolis IN USA irs Hosp, Indianapolis, IN USA Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA Indiana Univ Indianapolis IN USA Sch Med, Dept Med, Indianapolis, IN USA Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 Pathol, Indianapolis, IN 46202 USA Shaman Pharmaceut, S San Francisco, CA USA Shaman Pharmaceut S San Francisco CA USA maceut, S San Francisco, CA USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 6, volume: 44, anno: 2000,
pagine: 1624 - 1629
SICI:
0066-4804(200006)44:6<1624:CONZWA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CAPSULATUM ANTIGEN; BLASTOMYCOSIS; COCCIDIOIDOMYCOSIS; EFFICACY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Wheat, J Histoplasmosis Reference Lab, 1001 W 10th St,OPW 430, Indianapolis, IN 46202 USA Histoplasmosis Reference Lab 1001 W 10th St,OPW 430 Indianapolis IN USA 46202
Citazione:
J. Goldberg et al., "Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment of histoplasmosis in a murine model", ANTIM AG CH, 44(6), 2000, pp. 1624-1629

Abstract

Nikkomycin Z was tested both in vitro and in vivo for efficacy against Histoplasma capsulatum, Twenty clinical isolates were tested for susceptibility to nikkomycin Z in comparison to amphotericin B and itraconazole, The median MIC was 8 mu g/ml with a range of 4 to 64 mu g/ml for nikkomycin Z, 0.56 mu g/ml with a range of 0.5 to 1.0 mu g/ml for amphotericin B, and less than or equal to 0.019 mu g/ml for itraconazole, Primary studies were carried out by using a clinical isolate of H. capsulatum for which the MIC of nikkomycin Z was greater than or equal to 64 mu g/ml. In survival experiments,mice treated with amphotericin B at 2.0 mg/kg/dose every other day (QOD) itraconazole at 75 mg/kg/dose twice daily (BID), and nikkomycin Z at 100 mg/kg/dose BID survived to day 14, while 70% of mice receiving nikkomycin Z at20 mg/kg/dose BID and none of the mice receiving nikkomycin Z at 5 mg/kg/dose BID survived to day 14. All vehicle control mice died by day 12, Fungalburden was assessed on survivors. Mice treated with nikkomycin Z at 20 and100 mg/kg/dose BID had significantly higher CFUs per gram of organ weight in quantitative cultures and higher levels of Histoplasma antigen in lung and spleen homogenates than mice treated with amphotericin B at 2.0 mg/kg/dose QOD or itraconazole at 75 mg/kg/dose BID. Studies also were carried out with a clinical isolate for which the MIC of nikkomycin Z was 4 mu g/ml. All mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID survived until the end of the study at day 17 postinfection, while 30% of the untreated vehicle control mice survived. Fungal burden assessed on survivors showed similar levels of Histoplasma antigen in lung and spleen homogenates of mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID, The three surviving vehicle control mice had significantly higher antigen levels in lung and spleen than other groups (P < 0.05), The efficacy of nikkomycinZ at preventing mortality and reducing fungal burden correlates with in vitro susceptibility.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 08:14:14