Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

Unravelling the antifungal mode of action of curcumin by potential inhibition of CYP51B: A computational study validated in vitro on mucormycosis agent, Rhizopus oryzae.

Like human, fungi too are known to share lot of structural similarities amongst their CYPs (Cytochrome P450 super family of enzymes) which allows antifungal 'azole' compounds to interact with CYPs of human. Clotrimazole, an 'azole' antifungal drug, is a known inhibitor of fungal CYP named CYP51B. Curcumin, a phytochemical obtained from Curcuma longa has the ability to interact with several different human CYPs to induce inhibition. The sequence and the structural similarities amongst both human and fungal CYPs suggest a strong possibility for curcumin to interact with fungal CYP51B to behave like an antifungal agent. To test this hypothesis a study was designed involving mucormycosis agent, Rhizopus oryzae. The ability of curcumin to interact with fungal CYP51B was analysed computationally through molecular docking, MM-GBSA and Molecular Dynamics (MD) simulation assessment. Further, interaction profile for fungal CYP51B-curcumin was compared with human CYP3A4-curcumin, as there are published evidence describing curcumin as an inhibitor of human CYPs. Additionally, to validate in silico findings, an in vitro assay was performed to examine the antifungal potentials of curcumin on the R. oryzae. Conclusive results allow us to determine a plausible mode of action of curcumin to act as an antifungal against a mucormycosis agent.

Invasive Mucormycosis in Children With Malignancies: Report From the Infection Working Group of the Hellenic Society of Pediatric Hematology-Oncology.

Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.