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Key Points: Question: Does twice-annual mass azithromycin distribution prevent all-cause childhood mortality among children in Burkina Faso aged 1 to 59 months in the setting of seasonal malaria chemoprevention distribution? Findings: In this randomized trial of twice-yearly mass azithromycin distribution, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years) in the azithromycin group compared with 588 deaths over 58 547 person-years (10.0 deaths/1000 person-years) in the placebo group. The difference was not statistically significant. Meaning: Communities with mass azithromycin distribution had lower child mortality than controls, although the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P =.07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764 This cluster randomized placebo-controlled trial examines the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality in rural Burkina Faso. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the efficacy of mass distribution of azithromycin for trachoma control among Ethiopian children on mortality in communities. Results indicated that mass distribution of the drug was quite effective in reducing mortality.

A study to confirm if administration of biannual treatment can help eliminate ocular chlamydial infection in preschool children and compared the results with the World Health Organization recommendations for annual treatment is conducted. Results prove that administration of antibiotics biannually could eliminate ocular chlamydial infection.

A study was conducted to determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hypernedemic region of Ethiopia. The findings showed that ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution, slowly returning over 24 months and repeated treatments or other effective measures would be necessary for elimination.

The rate at which chlamydial infection returns to a population after mass treatment is determined and the treatment frequency required for elimination of ocular chlamydia form a community is estimated. The result indicates that elimination of infection in a hyperendynamic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2.Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14.Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization.Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92).Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21.Results: Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16).Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection.Trial Registration: ClinicalTrials.gov Identifier: NCT04332107. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. Methods: Randomized, placebo-controlled, doublemasked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. Main Outcome Measures: The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/ scar size, reepithelialization, and corneal perforation. Results: Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [log MAR]; 95% CI, -0.085 to 0.068; P=.82), infiltrate/scar size (P=.40), time to reepithelialization (P=.44), or corneal perforation (P >.99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P=.03) and ulcer location (P=.04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 log MAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P=.03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 log MAR better visual acuity with corticosteroids (-0.37 to -0.04; P=.02). Conclusions: We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. Application to Clinical Practice: Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. [ABSTRACT FROM AUTHOR]

Objectives: To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods: Baseline data from a 1:1 randomized, placebocontrolled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle- corrected visual acuity, infiltrate size, microbiological results, and patient demographics, for patients enrolled in the trial. Results: Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 log MAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%). Conclusions: The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. [ABSTRACT FROM AUTHOR]

Objective: To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates. Methods: Disk diffusion susceptibility testing for ciprofloxacin, moxifloxacin, and gatifloxacin was performed for all ocular isolates of S aureus at the Francis I. Proctor Foundation microbiology laboratory from January 1, 2005, to December 31, 2008. The medical records of patients with positive S aureus cultures were reviewed to determine topical or systemic fluoroquinolone use within the 3 months prior to culture. The Fisher exact test was used to compare the proportion of patients who used topical fluoroquinolones in the past 3 months among fluoroquinolone- sensitive and -resistant cases. Logistic regression was used to determine risk factors for fluoroquinolone resistance. Results: Of 200 S aureus cultures, 41 were resistant to ciprofloxacin, moxifloxacin, and gatifloxacin (20.5%). Fluoroquinolone- resistant S aureus isolates were from older patients (mean [SD] age, 65.5 [25.0] years) compared with fluoroquinolone-susceptible isolates (mean [SD] patient age, 52.1 [22.1] years) (P=.003). Use of fluoroquinolones within the 3 months before testing was more frequent in resistant isolates (29%) than in susceptible isolates (11%) (P=.005), as was recent hospitalization (22% of resistant isolates, 0% of susceptible isolates) (P<.001). In the multivariate regression analysis, topical fluoroquinolone use within 3 months was a significant predictor of fluoroquinolone resistance (P=.046), along with age, systemic immunosuppression, and topical fluoroquinolone use between 3 and 6 months before testing. Conclusion: Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures. [ABSTRACT FROM AUTHOR]

Objective: 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 itraconazole or caspofungin. Amphotericin B had significantly lower MICs compared with natamycin, but after correcting for the typical prescription dose, natamycin was superior. Conclusion: No single agent was universally most effective, but voriconazole and other triazoles demonstrated the broadest spectrum. Itraconazole and caspofungin were not effective against Fusarium species. Clinical Relevance: Fungal ulcers are commonly treated empirically; drugs are typically selected without regard to susceptibility data. The nonocular infectious disease literature suggests modern fungal susceptibility methods are clinically relevant, but ocular studies are limited. Our results suggest antifungal therapy might be tailored to individual organisms. [ABSTRACT FROM AUTHOR]

Context The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. Objective To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. Design, Setting, and Participants Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. Intervention A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. Main Outcome Measure Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. Results Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P<.001). Conclusions Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination. [ABSTRACT FROM AUTHOR]

Importance: Acute infectious conjunctivitis is a common ocular condition with major public health consequences., Objective: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment., Design, Setting, and Participants: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded., Main Outcomes and Measures: Pathogens were identified by unbiased RNA deep sequencing., Results: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens., Conclusion and Relevance: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.