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To characterize the susceptibility of filamentous fungi isolated from keratitis to amphotericin B, natamycin, caspofungin acetate, itraconazole, voriconazole, and posaconazole. Methods: Ninety isolates from fungal keratitis cases at Aravind Eye Hospital in South India were tested using macrobroth dilution for susceptibility to amphotericin B, natamycin, caspofungin, itraconazole, voriconazole, and posaconazole. The minimum inhibitory concentration (MIC) median and 90th percentile were determined. Results: The 90 isolates included 41 Aspergillus species, 38 Fusarium species, and 11 others. The triazoles and caspofungin had the lowest MICs against Aspergillus species; voriconazole, amphotericin B, and posaconazole had the lowest MICs against Fusarium species, and none of the Fusarium species were inhibited by itracona

Objective-To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis.Methods-The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not.Main Outcome Measures-The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a sub-analysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400.Results-Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P=.29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P=.48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P>.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P=.06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P=.07).Conclusions-Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole-and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes.

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BackgroundAntibiotics are a major tool in the WHO's trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued.MethodsSixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment.FindingsThe average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued.ConclusionIn some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary.Trial RegistrationClinicalTrials.gov NCT00221364

Aims-To conduct a preliminary clinical trial assessing whether adjunctive topical corticosteroids improve outcomes in bacterial keratitis and, if no difference is found, to determine the feasibility and sample size necessary for conducting a larger trial to answer this question.Methods-In this single center, double-masked clinical trial, 42 patients with culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were randomized to receive either topical prednisolone phosphate or placebo. All patients received topical moxifloxacin. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months, adjusting for enrollment BSCVA and arm. Other pre-specified outcomes included re-epithelialisation time, infiltrate/scar size, and adverse events.Results-Compared to placebo, the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI 0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar size at 3 weeks or 3 months. To have 80% power to detect a 2-line difference in acuity, 360 cases would be required.Conclusions-Although corticosteroid treatment resulted in a statistically significant delay in reepithelialisation, this did not translate to a significant difference in visual acuity, infiltrate/scar size, or adverse events. To assess the effect of steroids on acuity, a larger trial is warranted and feasible.

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Context Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued. Objective To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment. Design, Setting, and Participants A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005. Interventions At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually. Main Outcome Measure Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections. Results Overall, 14 897 of 16 403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P=.03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P=.049, adjusting for baseline prevalence). Conclusion Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level.