Publication:

Amphotericin B, itraconazole, posaconazole and isavuconazole minimum inhibitory concentration against 85 strains of Rhizopus spp, isolated from the patients having COVID-19 associated mucormycosis in North India

Background Mucormycosis cases are managed by extensive debridement of the affected tissues, with correction of predisposing risk factors and antifungal drugs. Amphotericin B is the drug of choice; however, few azoles also have a good activity against Mucorales. Therefore, the present study was done to determine the minimum inhibitory concentration (MIC) of antifungal drugs against Mucorales, causing COVID-19 associated mucormycosis in North India.

Methods After obtaining written and informed consent, we processed the received tissue, sputum, and gastric lavage samples as per standard mycological procedures. Subsequently, we determined itraconazole, posaconazole, isavuconazole and amphotericin B MIC against the isolated Mucorales (one from each patient) by broth microdilution using CLSIM38A3 guidelines.

Results We received 615 samples from the enrolled 269 patients with CAM. We observed broad aseptate hyphae in 329 fresh tissues, ten sputum and one gastric lavage sample, whereas 163 follow-up excised tissue had broad aseptate hyphae. In addition, 209 Mucorales were isolated with a predominance of Rhizopus arrhizus (n=183), followed by Rhizopus microsporus (n=21) and Rhizopus homothallicus (n=5). We determined MIC against 77 and 8 strains of R. arrhizus and R. microsporus, respectively. Posaconazole had the least MIC. 0.25, 1, 0.5, and 2µg/ml were the MIC50 of posaconazole, amphotericin B, isavuconazole and itraconazole against R. arrhizus strains, respectively, whereas it was 0.125, 0.1875, 0.5 and 2 µg/ml against R. microsporus, respectively.

Conclusions Lower posaconazole MIC makes it a preferred drug for managing the mucormycosis cases; however, availability and cost are the limitations. Thus, amphotericin B and itraconazole may be used in such conditions.