The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.

Abstract

OBJECTIVE:

To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.

METHODS:

This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.

MAIN OUTCOME MEASURES:

The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.

RESULTS:

A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycintreated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=0.18 logMAR; 95% CI, 0.30 to 0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=0.41 logMAR; 95% CI,0.61 to 0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=0.02 logMAR; 95% CI, 0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86).

CONCLUSIONS:

Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases.

APPLICATION TO CLINICAL PRACTICE:

Voriconazole should not be used as monotherapy in filamentous keratitis.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00996736

• Authors: N Venkatesh Prajna, Tiruvengada Krishnan, Jeena Mascarenhas, Revathi Rajaraman, Lalitha Prajna, Muthiah Srinivasan, Anita Raghavan, Catherine E Oldenburg, Kathryn J Ray, Michael E Zegans, Stephen D McLeod, Travis C Porco, Nisha R Acharya, Thomas M Lietman, Mycotic Ulcer Treatment Trial Group
• Journal: JAMA ophthalmology (JAMA Ophthalmol) Vol. 131 Issue 4 Pg. 422-9 (Apr 2013) ISSN: 2168-6173 [Electronic] United States
• PMID: 23710492 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Ophthalmic Solutions
• Pyrimidines
• Triazoles
• Natamycin
• Voriconazole

Topics

• Administration, Topical
• Adult
• Antifungal Agents (administration & dosage, adverse effects, therapeutic use)
• Corneal Perforation (microbiology)
• Corneal Ulcer (drug therapy, microbiology, physiopathology)
• Double-Blind Method
• Eye Infections, Fungal (drug therapy, microbiology, physiopathology)
• Female
• Fungi (isolation & purification)
• Humans
• Keratoplasty, Penetrating
• Male
• Middle Aged
• Mycoses (drug therapy, microbiology, physiopathology)
• Natamycin (administration & dosage, adverse effects, therapeutic use)
• Ophthalmic Solutions
• Pyrimidines (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Triazoles (administration & dosage, adverse effects, therapeutic use)
• Visual Acuity (physiology)
• Voriconazole
• Wound Healing (drug effects)