title: Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis.
abstract: OBJECTIVE
  To assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial.
  
  
  METHODS
  Experimental study using data from a randomized comparative trial.
  
  
  METHODS
  Of the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis.
  
  
  METHODS
  The Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed.
  
  
  METHODS
  The primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization.
  
  
  RESULTS
  A 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95% CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15-0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97; P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study.
  
  
  CONCLUSIONS
  Decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome.
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California.
authors.forename: Catherine Q
authors.initials: CQ
authors.lastname: Sun
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: Prajna
authors.initials: P
authors.lastname: Lalitha
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: N Venkatesh
authors.initials: NV
authors.lastname: Prajna
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: Rajarathinam
authors.initials: R
authors.lastname: Karpagam
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: Manoharan
authors.initials: M
authors.lastname: Geetha
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California.
authors.forename: Kieran S
authors.initials: KS
authors.lastname: O'Brien
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Oldenburg
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ray
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: McLeod
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California.
authors.forename: Nisha R
authors.initials: NR
authors.lastname: Acharya
authors.affiliation: F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, California. Electronic address: tom.lietman@ucsf.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lietman
mesh_terms: D000287:Administration, Topical; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002921:Cicatrix / Q000473:pathology; D057112:Corneal Perforation / Q000175:diagnosis; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D019573:Epithelium, Corneal / Q000502:physiology; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D015948:Keratoplasty, Penetrating; D008826:Microbial Sensitivity Tests; D010866:Natamycin / Q000494:pharmacology / Q000627:therapeutic use*; D009883:Ophthalmic Solutions; D062326:Re-Epithelialization; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology; D065819:Voriconazole / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D010866:Natamycin; D065819:Voriconazole
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