Prospective observational study on antifungal resistance in fungal keratitis in South India.

Objectives: Our primary objective was to identify the rate of anti-fungal resistance (including multidrug resistance) of fungal isolates cultured from fungal keratitis patients in South India. Our secondary objective was to identify associations between antifungal resistance and patient outcome. Subjects/Methods: 153 patients attending the cornea clinic at Aravind Eye Hospital, Madurai (May-August 2025) with culture positive fungal keratitis were enrolled in the study. Cultured isolates were evaluated for natamycin, amphotericin B, voriconazole and econazole MIC (n=151-153). MIC data were analysed by Kruskal-Wallis test followed by Dunn's multiple comparisons test. Patient disease outcome relative to isolate resistance was analysed by fisher's exact test (n=91). Results: There were high levels of resistance to all four antifungals, which were significantly elevated in Fusarium spp. and Aspergillus spp. isolates compared to other fungal genera (P<0.0001). Resistance of Fusarium spp. isolates (n=81) to: natamycin: 38.3%; amphotericin B: 93.8%; voriconazole: 97.5% and econazole: 76.5%. Resistance of Aspergillus spp. isolates (n=33) to: natamycin: 66.7%; amphotericin B: 87.9%; voriconazole: 6.1%; and econazole: 0%. Overall, fungal resistance to natamycin significantly correlated with a poor clinical outcome, P=0.0034, relative risk 1.7 (95% CI: 1.2-2.6). Conclusions: The majority of fungal isolates were resistant to multiple antifungals; none of the Fusarium isolates were susceptible to all four drugs, 15% were resistant to all of them. Resistance towards natamycin may worsen clinical outcome, particularly for infections caused by Aspergillus, even when susceptible to azoles. Our data supports the need for species specific MIC thresholds to have increased clinical utility.