Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh

Abstract

Aim: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis.

Methods: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial.

Results: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment.

Conclusions: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.

Figure 1

Flow of patients through the various stages of the trial.

Figure 2

Serial photographs of healing of ulcer, classified as severe, by 0.2% chlorhexidine. Study no 25, 15 year old male student, secondary to injury with fingernail. Fungus identified was Fusarium sp. (A) At presentation, with hypopyon, (B) 5th day, (C) 7th day, (D) 10th day, residual epithelial defect. Fully healed on day 26.

Figure 3

Serial photographs of healing of ulcer by 0.2% chlorhexidine. Study no 4, 45 year old female farmer, no history of injury. Fungus identified was Fusarium sp. (A) Ulcer at presentation, (B) fifth day, (C) 7th day. (D) Ulcer healed on 17th day.