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Organism, Minimum Inhibitory Concentration, and Outcome in a Fungal Corneal Ulcer Clinical Trial

Lalitha, Prajna MD; Prajna, N. Venkatesh FRCOphth; Oldenburg, Catherine E. MPH; Srinivasan, Muthiah MD; Krishnan, Tiruvengada MD; Mascarenhas, Jeena MD; Vaitilingam, C. M. MS; McLeod, Stephen D. MD; Zegans, Michael E. MD; Porco, Travis C. PhD, MPH; Acharya, Nisha R. MD, MS; Lietman, Thomas M. MD

doi: 10.1097/ICO.0b013e31823f8ae0
Clinical Science

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.

*Aravind Eye Care System, Madurai, India

F.I. Proctor Foundation, University of California San Francisco, California, USA

Aravind Eye Care System, Pondicherry, India

§Department of Ophthalmology, University of California, San Francisco, San Francisco, CA

Section of Ophthalmology, Dartmouth-Hitchcock Medical Center, Lebanon, NH

||Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH

**Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA.

Reprints: Thomas M. Lietman, F.I. Proctor Foundation, Room S309, 513 Parnassus Ave, UCSF, San Francisco, CA 94143-0412 (e mail:

Alcon, Inc, donated natamycin and Pfizer, Inc, donated voriconazole for the study. Funding for this research was from That Man May See and the South Asia Research Fund.

The Department of Ophthalmology at the University of California, San Francisco, is supported by a core grant from the National Eye Institute, EY02162.

Dr Acharya was supported by a National Eye Institute (K23EY017897) grant and a Research to Prevent Blindness Career Development Award. Dr. Lietman was supported by a National Eye Institute grant (U10-EY015114) and a Research to Prevent Blindness Award. Dr. Porco was supported by That Man May See Foundation at the University of California, San Francisco.

The sponsors did not have role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

The authors state that they have no proprietary interest in the products named in this article.

Received August 31, 2010

Accepted July 18, 2011

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.