Randomized Double-Masked Placebo-Controlled Trial for the Management of Pythium Keratitis: Combination of Antibiotics Versus Monotherapy

Abstract

Purpose:The aim of this study was to compare the efficacy of monotherapy (topical linezolid 0.2%) versus a combination of antibiotics (topical linezolid 0.2% and topical azithromycin 1%) for the treatment of Pythium insidiosum keratitis.Methods:Cases of P. insidiosum keratitis were prospectively randomized into group A on topical 0.2% linezolid along with topical placebo (sodium carboxymethyl cellulose [CMC] 0.5%) and group B on a combination of topical 0.2% linezolid and topical 1% azithromycin. Both groups were compared by proportion of both clinical resolution and worsening of keratitis along with the number of therapeutic penetrating keratoplasty (TPK) performed at 3 months.Results:We initially planned N = 66 patients but later limited to 20 (N = 10 in each group) patients owing to one interim analysis. The average size of the infiltrate in group A and B was 5.6 ± 1.5 mm and 4.8 ± 2.0 mm, respectively, with a mean Logarithm of the Minimum Angle of Resolution (logMAR) visual acuity of 2.74 ± 0.55 and 1.79 ± 1.19. At 3 months, from group A, 7 (70%) patients needed TPK and 2 patients had signs of resolution, whereas from group B, 6 (60%) patients achieved complete resolution (P = 0.0003) and 2 were improving while only 1 needed TPK (P = 0.02). The median duration of treatment in group A and B, with the study drugs, was 31 days (17.8–47.8) and 101.5 days (80–123.3), P value = 0.003, respectively. Final visual acuity at 3 months was 2.50 ± 0.81 and 0.75 ± 0.87, P = 0.02, respectively.Conclusions:A combination of topical linezolid and topical azithromycin was found to have superior efficacy than the monotherapy with topical linezolid for the management of Pythium keratitis.

Letter Regarding: Randomized Double-Masked Placebo-Controlled Trial for the Management of Pythium Keratitis: Combination of Antibiotics Versus Monotherapy

“…We read the article by Tanna et al 1 with great interest, and we must congratulate the authors. First, the authors have mentioned in the inclusion criteria that all the clinically diagnosed patients were subjected to 10% KOH+ 0.1% calcofluor white mount and Gram stain preparation along with the inoculation into blood agar, chocolate agar, non-nutrient agar with E. coli overlay, Sabouraud Dextrose Agar, potato dextrose agar, brain heart infusion, and thioglycollate broth.…”

Reply

“…We thank Gurunani et al for the comments and queries. 1 As an institute protocol for the management of microbial keratitis, all patients, who are having clinical suspicion of microbial keratitis, are routinely subjected to 10% KOH and 0.1% calcofluor white mount (CFW), Gram stain preparation, and inoculation into culture media including blood agar, chocolate agar, nonnutrient agar with Escherichia coli overlay, Sabouraud dextrose agar, potato dextrose agar, brain heart infusion, and thioglycollate broth. All these smear examinations for the identification of the Pythium filaments were performed by experienced microbiologists with the use of a fluorescence microscope for KOH + CFW mount, which is having good sensitivity and specificity 2 for differentiation of Pythium from fungal filaments.…”