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  • Fungal Keratitis: Natamycin Superior to Chlorhexidine

    By Lynda Seminara
    Selected by Russell N. Van Gelder, MD, PhD
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    Journal Highlights

    Ophthalmology, May 2022

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    Fungal keratitis is challenging to man­age, and treatment is often delayed in areas with limited access to care. Although natamycin has been the treatment of choice, it is costly, difficult to formulate, and not available globally. Recognizing the need for an afford­able, accessible option, Hoffman et al. compared chlorhexidine with natamycin in a nonin­feriority study. They found that natamycin produced better visual acuity and had fewer side effects than chlorhexidine. As a result, it should remain the preferred first-line therapy for fungal keratitis, they said.

    For this single-masked, randomized, controlled trial, the investigators enrolled adults with filamentous fungal infection managed at a tertiary-level ophthalmic hospital in Nepal. The infection was confirmed by a smear test or confocal microscopy. Participants were assigned randomly to receive topical treatment with 0.2% chlorhexidine or 5% natamycin. The main outcome measure was logMAR BCVA at three months. Secondary outcomes included the incidence of perforation or therapeutic penetrating keratoplasty within 90 days. Cases of mixed fungal and bacterial infections were excluded from the primary analy­sis but included in secondary analyses. The predetermined noninferiority threshold for efficacy was 0.15 logMAR.

    During the 17-month enrollment period (June 2019–November 2020), there were 354 eligible participants. Of these, 178 received chlorhexidine, and 176 received natamycin. After excluding those for whom 90-day outcomes were not available and cases of mixed bacte­rial-fungal infections, 284 participants remained for the primary analysis (141 chlorhexidine, 143 natamycin).

    The investigators found that outcomes in the natamycin-treated group were superior to those in the chlorhexidine-treated group. Patients treated with natamycin had significantly better BCVA at 90 days, after adjusting for baseline BCVA (p < .001). BCVA was approximately 3 lines better in the natamycin group. Perforations and emergency corneal grafts were more common in those treated with chlor­hexidine (13.7% vs. 5.8%; p = .018), and natamycin-treated cases were less likely to experience perforation or re­quire an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; p = .013).

    The authors suggest viewing these results in a global context. For example, if natamycin is not available, cautious use of chlorhexidine may be useful. Even so, this study highlights the need for natamycin to be readily available wherever fungal keratitis is a public health concern, said the authors. They recommend testing the safety of lower doses of chlorhexidine and exploring the possibility of a chlorhexidine-nat­amycin combination treatment for the disease.

    The original article can be found here.