Combined therapy with amphotericin B and caspofungin in an experimental model of disseminated histoplasmosis.
OBJECTIVE
To assess the effect of amphotericin B and caspofungin, as well as their combinations in the therapy of experimental disseminated histoplasmosis.


METHODS
BALB/c mice were intraperitoneally infected with four different strains of Histoplasma capsulatum and given to antifungal treatments. The response to intraperitoneal therapy with amphotericin B (0.5, 1.0, and 2.0 mg/kg of body weight) or caspofungin (10 mg/kg of body weight) and their combinations, was evaluated by the quantification of yeast colony-forming units (CFU) per gram of spleen or lung, from each animal. Additionally, the pathogen was monitored histopathologically in the excised organs. Data were analyzed with the Kruskall-Wallis and Tukey tests.


RESULTS
Caspofungin was more effective than amphotericin B in reducing the CFU/ g. A synergistic effect was observed when caspofungin (10 mg/ kg) was combined with amphotericin B (0.5 or 1.0 mg/kg). Significant differences in CFU values, H = 119.78 (P = 0.00001), were found among the treatment groups. However, statistical analyses did not reveal significant differences, H = 2.837 (P = 0.428), in the therapeutic responses with the four H. capsulatum strains tested.


CONCLUSIONS
Combined therapy with amphotericin B and caspofungin could represent an alternative treatment to be explored in severe human histoplasmosis.
Rodríguez-Arellanes
Gabriela
G
Departamento de Microbiología-Parasitología , Facultad de Medicina, Universidad Nacional Autónoma de Mexico. Departamentos de ***Bioquimica, ****Zoologia y *****Microbiologia, Escuela Nacional de Ciencias Biol6gicas, Instituto Polit&cnico Nacional.
Taylor
María Lucía
ML
Pérez-Torres
Armando
A
Curiel-Quesada
Everardo
E
Vargas-Mendoza
Carlos Fabián
CF
Martínez-Rivera
María Angeles
MA
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077336:Caspofungin; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006658:Histoplasma / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification; D006660:Histoplasmosis / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D055666:Lipopeptides; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013154:Spleen / Q000382:microbiology
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000666:Amphotericin B; D000077336:Caspofungin