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 eYcacy 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 eYcacy (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 eYcacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus ( Ophthalmologists working in a humid tropical environment are aware of how serious the problems of corneal ulcers caused by fungi can be. Often the onset follows a minor injury to the cornea in an agricultural worker, progresses slowly, and may be treated with traditional remedies before the suVerer presents with an advanced ulcer at an eye clinic. A prolonged period of pain and time unable to work follows, which subsistence farmers can often not aVord, ending in perforation of the cornea and evisceration or enucleation of the eye. The ophthalmologist frequently has no access to a microbiology laboratory, and specific antifungal drugs for the eye are not available.The proportion of suppurative keratitis due to filamentous fungi is sometimes underestimated. In reports from Bangladesh this proportion has varied from 23% 1 to 33%, 2 36%, 3 and 40%. 4 In southern Florida, fungi accounted for 35% of isolates.5 In Accra, Ghana, it was found that fungi alone were responsible for 49% of positive cultures, and if mixed fungal and bacterial infections were included, fungi occurred in 56% of cultures.6 A wide range of species of fungi have been isolated. The commonest genera are Aspergillus and Fusarium. The subject of mycotic keratitis has been thoroughly reviewed by Thomas. 7 In a search for stable, inexpensive antimicro...

Current Perspectives on Ophthalmic Mycoses

“…None of the severe ulcers was fully healed at 21 days, but three of those treated with chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7 and 36% were healed at 21 days by treatment with chlorhexidine and natamycin, respectively (319). When 5% natamycin was used instead of the 2.5% preparation, better results were obtained.…”

Mycotic Keratitis, a State-of-the-art Review

“…There are occasional reports of natamycin resistant Aspergillus spp. isolated from infected eyes (47) or natamycin unresponsiveness in patients with mycotic keratitis (48). Amphotericin B topical form or voriconazole are used for the treatment of suspected cases of FK caused by filamentous fungi reported in numerous case reports in the ophthalmic literature (49-51).…”

Fungal infections of the cornea

“…Polyhexamethylene biguanide, a general environmental biocide that exhibits good in vitro activity against various microorganisms, including fungi, in a concentration of 0.02%, was found to significantly reduce fungal growth in a rabbit model of F. solani keratitis. 38 A related compound, chlorhexidine (a bis-biguanide cationic antiseptic) was initially reported to show promising activity in mycotic keratitis in two clinical trials, 39,40 but not in subsequent studies. In a prospective, randomised, controlled, double-masked clinical study on patients with mycotic keratitis, a higher success rate was reportedly achieved with the use of 1% silver sulphadiazine ointment than with 1% miconazole ointment; although the response of keratitis due to Aspergillus spp was comparable in both groups, keratitis due to Fusarium spp responded better to silver sulphadiazine than to miconazole.…”