A Global Analysis of Cases of Mucormycosis Recorded in the European Confederation of Medical Mycology / International Society for Human and Animal Mycology (ECMM / ISHAM) Zygomyco.net Registry from 2009 to 2022

We analyzed mucormycosis data from the Zygomyco.net registry (2009-2022), encompassing cases from 16 countries. India, Russia and the Czech Republic provided the largest contributions. India reported the highest case number, consistent with its substantially higher incidence compared to that of high-income countries. Among the 382 patients with mucormycosis, 236 (61.8%) were male (male-to-female ratio 1.6). The median age was 48 years [interquartile range (IQR) 32-60]. There were 59 pediatric patients (median age ranging from < 1 month to 19 years). Diabetes mellitus type 2 was the most common underlying condition (39%), with significant geographic variation (> 70% of cases in India and Iran but only 6.9% in Europe). Hematologic malignancies (HM, 31.4%), the second most common underlying condition, were absent in India and Iran. The primary clinical presentations were rhino-orbito-cerebral mucormycosis (ROCM, 36.6%), pulmonary (33.2%) and cutaneous mucormycosis (17.5%). Patients with diabetes mellitus typically developed ROCM (55.9%), while pulmonary infections were more common in those with HM or hematopoietic cell transplantation (HCT) (47.5%, p < 0.001). Rhizopus was the leading fungal genus (58%), followed by Lichtheimia (13.7%) and Mucor (7%), with regional variations. Pulmonary infections in HM patients were linked to L. corymbifera and R. microsporus, while Apophysomyces spp. and Saksenaea spp. were more frequent in Indian healthcare-associated cutaneous cases. Concomitant infections were observed in 8.7% of patients with HM, complicating diagnosis and treatment. In most of them (57.1%), Aspergillus spp. was involved. Improved diagnostic practices, including direct microscopy and cultures, showed higher positivity rates, although PCR remained underutilized. Antifungal therapy, primarily with an amphotericin B formulation, combined with surgery, was the most common therapeutic approach. Overall mortality was high (47.8%), particularly in disseminated or advanced ROCM cases. Multivariable analysis identified older age, advanced ROCM, and HM/HCT as independent mortality risk factors (p < 0.05); whereas localized sinusitis and combined medical and surgical therapy were independently associated with improved outcomes (p < 0.006). This study underscores regional disparities in the mucormycosis epidemiology and species distribution. Improved early detection is needed, particularly in immunocompromised populations with HM. Enhanced surveillance and tailored public health strategies are crucial to address this ongoing global health threat.