Cryptococcal meningitis complicating systemic lupus erythematosus: two patients treated with flucytosine and amphotericin B.

Abstract

SUMMARY Two fatal cases of cryptococcal meningitis complicating adrenocorticosteroid-treated systemic lupus erythematosus are reported. In one patient who was treated with flucytosine alone, after an initial period of improvement cryptococci resistant to flucytosine were isolated, and subsequent amphotericin B treatment did not alter the progress of the disease. In the second patient, who received both drugs concurrently, resistant cryptococci did not appear and the patient recovered sufficiently to return home. Flucytosine-resistant mutants could be demonstrated in vitro in the original cryptococcal isolates from both patients. The use of flucytosine and amphotericin B in combination is discussed.

Cryptococcal meningitis in Chinese patients with systemic lupus erythematosus

“…Five of the 6 patients had a favorable response to induction therapy of amphotericin B or fluconazole combined with flucytosine, followed by long-term consolidation therapy with fluconazole. This was consistent with recommended treatments in previous studies [29,30]. In the present study, none of the patients had suffered relapse of CM while receiving long-term consolidation fluconazole therapy combined with glucocorticoids and immunosuppressive agents.…”

Criptococosis meníngea y lupus eritematoso sistémico: Reporte de un caso y revisión de la literatura

“…La dosis promedio recomendada es de 1 mg/kg/día, hasta acumular entre 1 y 1,5 gr 18 . El otro medicamento utilizado es 5-fluocitosina www.sochinf.cl la cual es mejor tolerada, menos tóxica y penetra mejor en el SNC; se describe, sin embargo, la emergencia de resistencia durante el tratamiento 19 . Se recomienda la utilización de ambos medicamentos en combinación, para luego seguir con fluconazol.…”

“…La óptima duración del tratamiento no ha sido determinada y dependerá de los resultados de las repetidas punciones lumbares o de las pruebas serológicas. Anfotericina B podría prevenir la multiplicación de hongos resistentes a 5-fluocitosina, mientras que las altas dosis iniciales de 5-fluocitosina, producen una actividad anticriptococcósica sin efectos tóxicos mientras la anfotericina B aumenta gradualmente su actividad en el transcurso de los días; además se ha reportado efectos sinérgicos entre los dos medicamentos 19 . La mortalidad alcanza hasta 54% y la mayoría de los fallecimientos ocurren en las primeras semanas de la infección 14,17 .…”

Therapy of fungal infections of the central nervous system

“…Ideal conditions are provided for selection of resistant mutants, as is the case with the administration of flucytosine. The population of most yeast isolates contains pre-existing flucytosine-resistant mutants, with a frequency of approximately 1/4x 106 cells, and the selection by the drug may occur in vivo as in vitro (Speller et al, 1977). Figure 2 shows in vitro selection of flucytosine-resistant mutants from an isolate of Crypt.…”

“…neoformans; similar resistant mutants colonized the patient's cerebrospinal fluid from the nineteenth day of flucytosine treatment. (Speller et al, 1977).…”