Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India

Abstract

IMPORTANCE Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients.Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). CONCLUSIONS AND RELEVANCEThis post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world.

Case Series of Rare Fungal Keratitides: Experiences from a Quaternary Eye Hospital in Sydney, Australia

“…Interestingly, both patients in our series failed voriconazole treatment despite a positive culture result demonstrating Scedosporium apiospermum and Purpureocillium lilacinum sensitivity to voriconazole (MIC level 0.5 µg/mL). This could be attributed to an increasing fungal resistance to voriconazole with a recent study (2022) demonstrating a 1.02-fold increase in resistance per year [35]. Hence, it is important to remain vigilant with monitoring patient symptoms and correlating with clinical signs to guide antifungal therapy even in the context of confirmed culture and sensitivity results.…”

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

“…47 Most data on the prevalence of resistance to antifungal agents are for isolates from systemic infections, with relatively few studies of corneal isolates, 32,39,50,51 although an increase in resistance for natamycin and voriconazole against Fusarium spp and Aspergillus spp has been reported. 52 We could nd no published evidence from the UK for a difference in the susceptibility pro le of common corneal isolates compared to isolates from other regions. Of potentially greater relevance in the short term, the overall pro le of fungal pathogens has changed since 2000 following a marked increase in the proportion of Fusarium spp associated with contact lens wear, a fungus that is typically relatively resistant to antifungals.…”

Benzyl isothiocyanate improves the prognosis of Aspergillus fumigatus keratitis by reducing fungal load and inhibiting Mincle signal pathway

“…FK is a complex, refractory keratopathy that may be attributed to the limited efficacy of current antifungal drugs and excessive inflammatory response ( Ung et al, 2019 ; Prajna et al, 2022 ). BITC is a secondary metabolite extracted from the cruciferous species and has received attention for its broad pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant activities.…”