By Stan Deresinski, MD, FACP, FIDSA
SYNOPSIS:Mucormycosis continues to be associated with a high mortality rate. Polymerase chain reaction may speed diagnosis and allow earlier initiation of therapy. There appears to be no evidence supporting the use of combination as opposed to single agent (liposomal amphotericin B) therapy.
SOURCE: Denis B, Resche-Rigon M, Raffoux E, et al. Epidemiology, clinical manifestations, treatment, and outcome of mucormycosis: A review of 77 cases from a single center in France. Open Forum Infect Dis 2024;11:ofae426.
Denis and colleagues reviewed the records of 77 patients with mucormycosis seen at the Hôpital Saint-Louis in Paris diagnosed in 2006 through 2020. Their median age was 54 years and 60% were male. The incidence increased over time at least in part due to the introduction of polymerase chain reaction (PCR) testing for the organism in 2015 and routine regular screening of high-risk burn patients.
Of the 77 patients, 46 (60%) had a hematolymphoid malignancy, including 25 (57%) with acute leukemia, eight (17%) with myelodysplastic syndrome, and six (1%) with lymphoma. Twenty patients (46%) had received an allogeneic hematopoietic stem cell transplant, with 12 of these having developed graft-versus-host disease. Neutropenia was present in 30 patients (39%) overall and in 29/46 (63%) with a hematolymphoid malignancy. Eighteen patients had a thermal burn involving a median total burn surface area of 58%. Nineteen (25%) patients had diabetes mellitus, but this was a sole risk factor in only seven patients (9%).
Infection involved the lungs in 32 patients (42%); computerized tomography demonstrated a halo sign in 11 (26%) and reverse halo sign in three — but these were present only in those with hematolymphoid malignancy. Among the 28 patients (36%) with rhino-orbital-cerebral infection, three had intra-orbital extension and six had intracranial extension. Skin lesions were present in 24 patients (31%). Nine patients had disseminated infection, with six of these occurring in the context of a hematolymphoid malignancy.
The diagnosis of mucormycosis was made by culture and/or quantitative PCR (qPCR) in 72 cases (94%), while in five cases it was based on morphology in tissue samples. Among hematology cases, qPCR of at least one serum sample was positive in 22 (81%) of 27 patients in whom the test was performed. The most frequently identified genera were Rhizopus and Mucor. A concomitant infection with another mold was present in 24 patients (31%) — mostly due to Aspergillus (n =18), especially in those with hematolymphoid malignancies, and Fusarium (n = 6), with all of the latter being “cutaneous” infections in burn patients.
Most patients (90%) received liposomal amphotericin B, which was given for a median duration of 25 days. Other frequently prescribed therapies were posaconazole in 32 patients (42%) and isavuconazole in 16 patients (21%). Combination therapy was administered to 18 patients (23%). Forty-three patients (56%) also had surgical therapy. Immunosuppressive therapy was tapered in 13/34 patients (38%).
The three-month survival was 40%, while the overall survival to the end of follow-up was 25%, with 43% of the fatalities related to mucormycosis. There was no significant difference in mortality between patients with hematolymphoid malignancies, diabetes mellitus, or burn injury. In multivariate analysis, older age at diagnosis and disseminated infection each was significantly associated with mortality at three months, while only surgery was associated with improved survival. There was no significant difference between combination and monotherapy.
Commentary
The results from this single center in Paris are compatible with those of a recent French national surveillance report of 555 cases seen over 10 years.1 Almost two-thirds of patients in that study had a hematological malignancy. The 90-day mortality was 55.8%. Only age at diagnosis and the presence of disseminated disease were independent risk factors for greater three-month mortality while, in contrast to the study of Denis et al, surgery was associated with reduced mortality, as was diagnosis after 2015, when PCR diagnostic testing was introduced.
The value of surgery depends on the site of infection. While it does not play a role in purely disseminated infection, it may be critically important in accessible localized infections, such as rhino-orbital-cerebral infection and, less commonly, some pulmonary infections. In at least some of these cases, it may be critical to survival.
It generally is agreed that liposomal amphotericin B is the treatment of choice. Posaconazole and isavuconazole are used, often in combination with this polyene preparation. Denis and colleagues did not identify a benefit from combination therapy as opposed to monotherapy and this also was true in the study by Gouzien et al.1 In addition, no benefit of combination therapy was found in a retrospective study of 82 patients at Stanford.2
Early diagnosis and therapeutic intervention provide the best chance of effecting a favorable outcome of this serious infection. In this regard, the use of PCR is the most effective diagnostic approach available. The test used in France is reported to have a sensitivity and specificity of 85.2% and 89.8%, respectively, with positive and negative predictive values of 52.3% and 97.9%, respectively.3
References
- Gouzien L, Che D, Cassaing S, et al; French Mycoses Study Group. Epidemiology and prognostic factors of mucormycosis in France (2012-2022): A cross-sectional study nested in a prospective surveillance programme. Lancet Reg Health Eur 2024;45:101010.
- Lu B, Ha D, Shen S, et al. Combination antifungal therapy for invasive mucormycosis in immunocompromised hosts: A single-center experience. Open Forum Infect Dis 2024;11:ofae103.
- Millon L, Caillot D, Berceanu A, et al. Evaluation of serum mucorales polymerase chain reaction (PCR) for the diagnosis of mucormycoses: The MODIMUCOR prospective trial. Clin Infect Dis 2022;75:777-785.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.