Why Prior Fluconazole Use Is Associated with an Increased Risk of Invasive Mold Infections in Immunosuppressed Hosts: An Alternative Hypothesis

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Abstract
SIR—I read with interest the recently published review by Singh [1]. Dr. Singh nicely summarized the evidence suggesting that prior use of fluconazole results in an increase in invasive mold infections—most notably, invasive aspergillosis (IA)—both in allogeneic bone marrow transplant (BMT) recipients and in other patients considered to be at high risk, such as some solid-organ transplant recipients. She speculates that a phenomenon of overcoming “colonization resistance,” perhaps analogous to that initially described with the use of bacterial prophylaxis in neutropenic patients [2], could account for this shift in the epidemiology of invasive fungal infections in immunosuppressed hosts. This phenomenon is a likely explanation for the emergence of non-albicans Candida species (e.g., C. krusei and C. glabrata) that are resistant to fluconazole in at-risk patients who receive pretreatment with this agent. This concept is supported by a recent large autopsy study that compared BMT recipients who received fluconazole prophylaxis with those who did not. Invasive candidiasis (IC) due to the aforementioned non-albicans Candida species predominantly occurred in BMT recipients who received prophylactic fluconazole, and it also occurred later in this group than it did in the group who did not receive such treatment (the average time to death due to IC following BMT was 38 and 25 days for the 2 patient groups, respectively) [3].