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We read with interest the report by Sradhanjali et al(1) demonstrating more effective antifungal activity of combination of Natamycin and voriconazole than single-use in vitro treatment. It should be noted, however, that given the small sample size, these results should be confirmed with a larger dataset.
Caution should be exercised when inferring results from in vitro studies because it always do not translate to in vivo models and are inconsistent. In our hands, we found treatment success when adding topical voriconazole 1% with natamycin 5% in recalcitrant full thickness infiltrate cases of fungal keratitis. This may be because topical natamycin acts superficially whereas voriconazole, though not as effective as Natamycin, takes care of the deeper infiltration because it has better penetration than Natamycin. Sharma et al (2) also concluded that topical voriconazole seems to be a useful adjunct to natamycin in fungal keratitis not responding to topical natamycin. Debridement of ulcer also helps in these cases giving way for the drug to act and reducing the fungal load.
Given the poor susceptibility and clinical outcomes among Fusarium ulcers treated with voriconazole, Sun et al(3) recommended against using voriconazole as a first-line therapy for Fusarium keratitis. Li et al(4) recommends against combination therapy because of possible interactions in mechanism of drugs. We believe that combination therapy as a first line of treatment may compound the pr...
Given the poor susceptibility and clinical outcomes among Fusarium ulcers treated with voriconazole, Sun et al(3) recommended against using voriconazole as a first-line therapy for Fusarium keratitis. Li et al(4) recommends against combination therapy because of possible interactions in mechanism of drugs. We believe that combination therapy as a first line of treatment may compound the problem of drug resistance. Though increasing azole resistance is common, resistance to natamycin is not observed(5). So, we woud like to drive the point that topical Natamycin should be the standard first line of drug in treating fungal keratitis and topical voricanazole can serve as adjunctive therapy in recalcitrant cases. Studies to measure aqueous humor concentrations of drugs may be needed to compare with the MIC to find correlation between in vivo and in vitro studies.
1. Sradhanjali S, Yein B, Sharma S, Das S. In vitro synergy of natamycin and voriconazole against clinical isolates of Fusarium, Candida, Aspergillus and Curvularia spp. Br J Ophthalmol. 2018; 102(1):142-145.
2. Sharma N, Chacko J, Velpandian T, Titiyal JS, Sinha R, Satpathy G, Tandon R, Vajpayee RB. Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology. 2013; 120(4):677-81.
3. Sun CQ, Lalitha P, Prajna NV, Karpagam R, Geetha M, O'Brien KS, Oldenburg CE, Ray KJ, McLeod SD, Acharya NR, Lietman TM. Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis. Ophthalmology. 2014; 121(8):1495-500.
4. Li L, Wang Z, Li R, Luo S, Sun X. In vitro evaluation of combination antifungal activity against Fusarium species isolated from ocular tissues of keratomycosis patients. American journal of ophthalmology. 2008; 146(5):724-8.
5. Prajna NV, Lalitha P, Rajaraman R, Krishnan T, Raghavan A, Srinivasan M, O’Brien KS, Zegans M, McLeod SD, Acharya NR, Keenan JD. Changing Azole Resistance: A Secondary Analysis of the MUTT I Randomized Clinical Trial. JAMA ophthalmology. 2016; 134(6):693-6.