Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial

Abstract

Purpose: To analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole and to assess the relationship between organism, MIC, and clinical outcome.

Methods: Data were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity, infiltrate/scar size, time to reepithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole were done according to Clinical and Laboratory Standards Institute standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC were assessed.

Results: Of the 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly isolated organisms. MIC was significantly different across the groups of organisms (P = 0.0001). A higher MIC was significantly associated with an increased likelihood of perforation [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.02-4.04; P = 0.04]. There was no significant association between MIC and 3-week visual acuity (OR, 0.058; 95% CI, -0.01 to 0.13; P = 0.11), 3-month visual acuity (OR, 0.01; 95% CI,-0.08 to 1.04; P = 0.79), 3-week infiltrate/scar size (OR, 0.12, 95% CI, -0.02 to 0.27; P = 0.10), 3-month infiltrate/scar size (OR, 0.12; 95% CI, -0.02 to 0.25; P = 0.09), or time to reepithelialization (hazards ratio, 1.19; 95% CI, 0.98-1.45; P = 0.08).

Conclusion: A higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.

Figure 1

Results of suceptibility testing, by organism and antifungal. MICs to natamycin are represented by black points, and to voriconazole by grey points. The number of cases with a particular MIC is represented by the area of the point.