Response to therapy in patients with cryptococcosis and AIDS: association with in vitro susceptibility to fluconazole / Respuesta al tratamiento en pacientes con criptococosis y sida: relación con la sensibilidad in vitro al fluconazol

Background. The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. Aims. To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. Methods. This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. Results. This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p = 0.65) or survival time free of failure or relapse (p = 0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. Conclusions. In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment (AU)

Antecedentes. Las implicaciones de la resistencia de Cryptococcus neoformans al fluconazol en el tratamiento de pacientes infectados con esta levadura no han sido completamente definidas debido a hallazgos discordantes obtenidos previamente. Objetivos. Dilucidar la influencia de la resistencia de C. neoformans al fluconazol en el tratamiento de los pacientes con criptococosis y sida. Métodos. En este estudio se compara retrospectivamente la evolución clínica de los pacientes con criptococosis según el grado de resistencia al fluconazol de los aislamientos de C. neoformans obtenidos de ellos. Resultados. Se incluyeron 71 episodios de criptococosis definidos por el aislamiento de C. neoformans de pacientes con la micosis, que se distribuyeron de la siguiente manera: 36 aislamientos fueron sensibles, 20 sensibles dosis-dependiente y 15 resistentes. En la fase de consolidación, cinco fallos en el proceso de tratamiento tuvieron lugar: dos en pacientes con aislamientos sensibles, dos en pacientes con aislamientos dosis-dependiente y uno en un paciente con un aislamiento resistente. Durante la fase de mantenimiento se presentaron 4 recurrencias en los 33 pacientes que tuvieron seguimiento (12%), ninguna de las cuales ocurrió en el grupo con aislamientos resistentes. No se encontraron diferencias estadísticamente significativas en el tiempo de supervivencia de los casos sin fallo terapéutico (p = 0.65) o en el tiempo de supervivencia de los casos sin fallo terapéutico o recaída (p = 0.38). Estos resultados no se modificaron cuando fueron evaluados en un modelo de regresión de Cox en el que se incluyeron la edad, el conteo de linfocitos T CD4 y el uso de terapia antirretroviral. Conclusiones. En pacientes con VIH y criptococosis la resistencia de C. neoformans a fluconazol parece no incrementar el riesgo de fallo terapéutico o recaída (AU)

Response to therapy in patients with cryptococcosis and AIDS: Association with in vitro susceptibility to fluconazole.

BACKGROUND: The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. AIMS: To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. METHODS: This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. RESULTS: This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p=0.65) or survival time free of failure or relapse (p=0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. CONCLUSIONS: In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment.