title: Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: Prajna
authors.initials: P
authors.lastname: Lalitha
authors.forename: N Venkatesh
authors.initials: NV
authors.lastname: Prajna
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Oldenburg
authors.forename: Muthiah
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Tiruvengada
authors.initials: T
authors.lastname: Krishnan
authors.forename: Jeena
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: C M
authors.initials: CM
authors.lastname: Vaitilingam
authors.forename: Stephen D
authors.initials: SD
authors.lastname: McLeod
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zegans
authors.forename: Travis C
authors.initials: TC
authors.lastname: Porco
authors.forename: Nisha R
authors.initials: NR
authors.lastname: Acharya
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lietman
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology; D005658:Fungi / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010866:Natamycin / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D014792:Visual Acuity; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D010866:Natamycin; D065819:Voriconazole