Effect of neutropenia and treatment delay on the response to antifungal agents in experimental disseminated candidiasis.
Antimicrob Agents Chemother
; 51(1): 285-95, 2007 Jan.
Article
en En
| MEDLINE
| ID: mdl-17088486
ABSTRACT
Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophils and the timely administration of antifungal agents are likely to be critical factors for a favorable therapeutic outcome of this syndrome. The effect of neutropenia on the temporal profile of the burden of Candida albicans in untreated mice and those treated with amphotericin B was determined using a pharmacodynamic model of disseminated candidiasis. A mathematical model was developed to describe the rate and extent of the C. albicans killing attributable to neutrophils and to amphotericin B. The consequences of a delay in the administration of amphotericin B, flucytosine, or micafungin were studied by defining dose-response relationships. Neutrophils caused a logarithmic decline in fungal burden in treated and untreated mice. The combination of amphotericin B and neutrophils resulted in a high rate of Candida killing and a sustained anti-C. albicans effect. In neutropenic mice, 5 mg/kg of body weight of amphotericin B was required to prevent progressive logarithmic growth. An increased delay in drug administration resulted in a reduction in the maximum effect to a point at which no drug effect could be observed. Neutrophils and the timely initiation of antifungal agents are critical determinants in the treatment of experimental disseminated candidiasis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Candidiasis
/
Antifúngicos
/
Neutropenia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos