Antifungal resistance, clinical outcome and clinico-microbiological correlation in ocular infections due to common melanized fungi Curvularia lunata and Lasiodiplodia theobromae in South India

<b>Aim.</b> Melanized fungi were rarely studied for their antifungal resistance (AFR) or clinical outcome, despite rising incidence of melanized fungal ocular infections and AFR in general. We report the antifungal resistance patterns, clinical outcome and clinico-microbiological correlation in two commonly isolated melanized fungi from ocular infections, <i>Curvularia lunata</i> and <i>Lasiodiplodia theobromae</i>, at a tertiary eyecare centre in South India.<b>Gap statement</b>. Despite melanized fungi accounting for a significant proportion of ocular fungal infections in the Indian subcontinent, and despite there being a limited selection of effective antifungal agents available for these infections, the existing data and studies on these issues remain sparse. Therefore, this study aimed to investigate the prevalence of antifungal resistance in two of the most common melanized fungal pathogens in ocular infections, <i>Curvularia lunata</i> and <i>Lasiodiplodia theobromae</i> and correlate it with the treatment given and the clinical outcome in patients.<b>Methodology.</b> Electronic medical records provided the clinical data. Standard broth microdilution was performed for antifungal susceptibility testing (AFST) in 30 isolates (17 <i>C</i>. <i>lunata</i> and 13 <i>L</i>. <i>theobromae</i>) for amphotericin B and natamycin (polyenes): voriconazole, ketoconazole, posaconazole, itraconazole and fluconazole (azoles) and caspofungin (echinocandin). Multidrug resistance (MDR) was defined as resistance to more than or equal to two classes of antifungals. DNA sequencing was performed for the isolates for species confirmation. The multivariate analysis was done for determining poor prognostic factors.<b>Results.</b> AFST showed highest susceptibility of study isolates for voriconazole (83.3% isolates), followed by natamycin (80%), fluconazole (80%), itraconazole (76.7%), ketoconazole (70%), posaconazole (66.7%), caspofungin (66.7%) and lastly amphotericin B (63.3%). All patients empirically received topical natamycin; additional oral ketoconazole/intraocular voriconazole was administered in select few. MDR was strongly associated with poor clinical outcome (multivariate analysis: <i>P</i> = 0.03, odds ratio = 7.8). All patients had microbial keratitis, one progressed to endophthalmitis. Additionally, therapeutic penetrating keratoplasty was required in 40% of cases. Globe salvage was possible in 80% patients, though good visual outcome was seen in only half of them. Both, anatomical and visual outcomes, were poor in 20% of patients. DNA sequencing showed <i>C. lunata</i> as the highest study species.<b>Conclusion.</b> <i>C. lunata</i> and <i>L. theobromae</i> showed varying <i>in vitro</i> antifungal susceptibility and clinical outcome in ocular infections. Voriconazole had significantly higher activity, while amphotericin B had lower activity <i>in vitro</i> for these melanized fungi. MDR isolates showed poorer clinical outcome.