Antifungal resistance of ocular isolates from fungal keratitis patients in South India, and its influence on clinical outcomes

AimsPrimary objective: To determine the minimum inhibitory concentration (MIC) of key antifungal drugs (natamycin, amphotericin B, voriconazole and econazole) against fungal isolates cultured from fungal keratitis patients in South India. Secondary objective: to ascertain correlations between antifungal resistance and patient outcome. MethodsIn this prospective observational study, MIC values were determined for fungal isolates cultured from 153 patients, with samples collected between May - August 2025. Clinical characteristics were collected at baseline, one-week and one-month following enrolment to the study. Mean antifungal MIC per fungi genera were compared. Statistical differences in MIC and patient characteristics were determined via multiple logistic or linear regression. Significance for participant outcome against resistant/non-resistant fungi were determined by Fishers exact test. ResultsResistance of Fusarium spp. isolates to: natamycin: 38.3%; amphotericin B: 93.8%; voriconazole: 97.5% and econazole: 76.5%. Resistance of Aspergillus spp. isolates to: natamycin: 66.7%; amphotericin B: 87.9%; voriconazole: 6.1%; and none were resistant to econazole. Natamycin MIC correlated with worse baseline (P[≤]0.01) and one-week (P[≤]0.05) visual acuity and ulcer severity. Poor patient outcomes (non-healing or therapeutic keratoplasty) were elevated 6.5x where the infection was caused by natamycin resistant Aspergillus, compared to sensitive Aspergillus strains (P[≤]0.05). ConclusionThe majority of fungal isolates were resistant to multiple antifungals, none of the Fusarium isolates were sensitive to all four drugs, and 15% were resistant to all four drugs. Aspergillus isolates had high levels of resistance to the polyenes, but remained largely susceptible to the azoles. Overall, worse patient outcomes were associated with increased natamycin MIC. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSFungal keratitis is a major cause of blindness worldwide, disproportionately affecting those across the tropics, with incidence increasing across temperate climates. The majority of cases are caused by the filamentous fungi Fusarium spp. and Aspergillus spp.. Antifungal resistance is poorly characterised in fungal keratitis. What this study addsWe report the fungal aetiology and the minimum inhibitory concentration (MIC) against natamycin, amphotericin B, voriconazole and econazole of isolates cultured from 153 patient corneal scrape samples between May - August 2025 at a South Indian hospital. We found high levels of fungal resistance, with Fusarium isolates having high levels of resistance to both polyenes and azoles. Aspergillus isolates showed good azole sensitivity, but high levels of resistance to polyenes. Aspergillus resistance to natamycin correlated with worse clinical outcomes at one-month. Natamycin resistance contributed to worse visual acuity and ulcer severity at baseline and one-week follow-up across all fungi. How this study might affect research, practice or policyOur study confirmed that natamycin was best available first-line treatment for Fusarium. Aspergillus isolates were mostly resistant to natamycin and amphotericin B, and this impacted patient outcomes. SynopsisWe identified high incidence of multi-drug resistant fungi, and that patients were more likely to have a poor clinical outcome if the fungal isolate was resistant to natamycin. This was most pronounced for Aspergillus isolates.