Multidrug antifungal resistance and clinical outcomes in fungal keratitis: a prospective study in a South Indian population.

Abstract

Objectives: Our primary objective was to identify the rate of antifungal 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 minimum inhibitory concentration (MIC; n = 151-153). MIC data were analysed by Kruskal-Wallis test followed by Dunn's multiple comparisons. 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). Fusarium spp. isolates (n = 81) resistant to: natamycin: 38.3%; amphotericin B: 93.8%; voriconazole: 97.5%; and econazole: 76.5%. Aspergillus spp. isolates (n = 33) resistant to: natamycin: 66.7%; amphotericin B: 87.9%; voriconazole: 6.1%; and econazole: 0%. Overall, fungal resistance to natamycin significantly correlated with an adverse 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, and 28% were resistant to all of them. Resistance to natamycin may worsen clinical outcome, particularly for infections caused by Aspergillus, even when susceptible to azoles. Our data support the need for species-specific MIC thresholds to have increased clinical utility.