Fumagillin Shortage: How to Treat Enterocytozoon bieneusi Microsporidiosis in Solid Organ Transplant Recipients in 2024?

Abstract

Intestinal microsporidiosis caused by Enterocytozoon bieneusi is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication. We aimed to describe therapeutic management of E. bieneusi infections in this context. We conducted a French nationwide observational retrospective study on reported cases of E. bieneusi infections in SOT recipients. We identified 154 cases: 64 (41.6%) were managed by simply modifying the immunosuppressive regimen, 54 (35.1%) were given fumagillin, and 36 (23.4%) were given nitazoxanide. Clinical remission rate ranged from 77.8% to 90.7% and was not significantly different between therapeutic strategies but tended to be lower with nitazoxanide. Stool negativization rate was highest with fumagillin (91.7%) and lowest with nitazoxanide (28.6%). Relapses occurred in 6.9% of cases and were more frequent with nitazoxanide (14.3%). This study shows that tapering immunosuppression can result in a satisfactory remission rate but is sometimes accompanied by relapses. Nitazoxanide had limited effectiveness, whereas fumagillin had good results that provide a solid rationale for bringing fumagillin back to market.

Trial registration number: ClinicalTrials.gov ID: NCT05417815.

Keywords: Enterocytozoon bieneusi; infectious diarrhea; microsporidiosis; nitazoxanide; solid organ transplant.

FIGURE 1

Serum creatinine values at microsporidiosis diagnosis according to therapeutic management group. The red line at 175 μmol/L represents the maximum creatinine value beyond which fumagillin is contraindicated according to the safety notice. MIT: modification of immunosuppressive treatment.

FIGURE 2

Graphical representation of clinical remission times according to treatment. Clinical remission times (censored data) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. The analysis was carried out on 96 data, 58 clinical remission times not being specified. MIT: modification of immunosuppressive treatment.

FIGURE 3

Graphical representation of stool negativization times according to treatment. Times to stool negativization (censored data) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. MIT: modification of immunosuppressive treatment.