@article {821, title = {Gut resistome of preschool children after prolonged mass azithromycin distribution: a cluster-randomized trial.}, journal = {Clin Infect Dis}, year = {2021}, month = {2021 May 26}, abstract = {

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. While the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.

}, issn = {1537-6591}, doi = {10.1093/cid/ciab485}, author = {Arzika, Ahmed M and Maliki, Ramatou and Abdou, Amza and Mankara, Alio K and Harouna, Abdoul N and Cook, Catherine and Hinterwirth, Armin and Worden, Lee and Zhong, Lina and Chen, Cindi and Ruder, Kevin and Zhou, Zhaoxia and Lebas, Elodie and O{\textquoteright}Brien, Kieran S and Oldenburg, Catherine E and Le, Victoria and Arnold, Benjamin F and Porco, Travis and Keenan, Jeremy D and Lietman, Thomas M and Doan, Thuy} } @article {176, title = {Evaluation of Metagenomic Deep Sequencing as a Diagnostic Test for Infectious Keratitis.}, journal = {Ophthalmology}, year = {2020}, month = {2020 Jul 17}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2020.07.030}, author = {Lalitha, Prajna and Prajna, N Venkatesh and Sikha, Misra and Gunasekaran, Rameshkumar and Hinterwirth, Armin and Worden, Lee and Chen, Cindi and Zhong, Lina and Liu, Zijun and Lietman, Thomas M and Seitzman, Gerami D and Doan, Thuy} } @article {201, title = {Indirect effect of oral azithromycin on the gut resistome of untreated children: a randomized controlled trial.}, journal = {Int Health}, year = {2020}, month = {2020 Jun 17}, abstract = {

BACKGROUND: Antibiotic use by one individual may affect selection for antimicrobial resistance in close contacts. Here we evaluated whether oral antibiotic treatment of one child within a household affected the gut resistome of an untreated cohabiting child.

METHODS: Households with at least two children \<5\ y of age were randomized in a 1:1 fashion to a 5d course of azithromycin or placebo. To evaluate indirect effects of azithromycin treatment on the gut resistome, we randomly assigned one child in the house to azithromycin and one to placebo. In placebo households, each child received placebo. We performed DNA sequencing of rectal swabs collected 5\ d after the last antibiotic dose. We estimated risk ratios for the presence of genetic resistance determinants at the class level using modified Poisson models for children in azithromycin households compared with placebo households and assessed the composition of the resistome using permutational analysis of variance (PERMANOVA).

RESULTS: Of 58 children (n = 30 azithromycin households, n = 28 placebo households) with post-treatment rectal swabs, genetic resistance determinants were common but there was no significant difference at the class (p = 0.54 for macrolides) or gene (p = 0.94 for structure by PERMANOVA, p = 0.94 for diversity) level between untreated children in azithromycin households compared with placebo households.

CONCLUSIONS: The results are encouraging that one child{\textquoteright}s antibiotic use may not influence the resistome of another child. Trial registration: ClinicalTrials.gov NCT03187834.

}, issn = {1876-3405}, doi = {10.1093/inthealth/ihaa029}, author = {Oldenburg, Catherine E and Hinterwirth, Armin and Worden, Lee and Sie, Ali and Dah, Clarisse and Ouermi, Lucienne and Coulibaly, Boubacar and Zhong, Lina and Chen, Cindi and Ruder, Kevin and Lietman, Thomas M and Keenan, Jeremy D and Doan, Thuy} } @article {71, title = {Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution.}, journal = {N Engl J Med}, volume = {383}, year = {2020}, month = {2020 11 12}, pages = {1941-1950}, abstract = {

BACKGROUND: Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.

METHODS: We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants{\textquoteright} gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.

RESULTS: Over the entire 48-month period, the mean ({\textpm}SD) coverage was 86.6{\textpm}12\% in the villages that received placebo and 83.2{\textpm}16.4\% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95\% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95\% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.

CONCLUSIONS: Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).

}, keywords = {Anti-Bacterial Agents, Azithromycin, Child Mortality, Child, Preschool, Drug Resistance, Bacterial, Female, Gastrointestinal Microbiome, Humans, Infant, Macrolides, Male, Mass Drug Administration, Metagenome, Niger, Sequence Analysis, DNA}, issn = {1533-4406}, doi = {10.1056/NEJMoa2002606}, author = {Doan, Thuy and Worden, Lee and Hinterwirth, Armin and Arzika, Ahmed M and Maliki, Ramatou and Abdou, Amza and Zhong, Lina and Chen, Cindi and Cook, Catherine and Lebas, Elodie and O{\textquoteright}Brien, Kieran S and Oldenburg, Catherine E and Chow, Eric D and Porco, Travis C and Lipsitch, Marc and Keenan, Jeremy D and Lietman, Thomas M} } @article {86, title = {Post-antibiotic Ocular Surface Microbiome in Children: A Cluster-Randomized Trial.}, journal = {Ophthalmology}, volume = {127}, year = {2020}, month = {2020 08}, pages = {1127-1130}, keywords = {Anti-Bacterial Agents, Child, Cornea, Humans, Microbiota, Randomized Controlled Trials as Topic}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2020.02.014}, author = {Doan, Thuy and Hinterwirth, Armin and Worden, Lee and Arzika, Ahmed M and Maliki, Ramatou and Chen, Cindi and Zhong, Lina and Zhou, Zhaoxia and Acharya, Nisha R and Porco, Travis C and Keenan, Jeremy D and Lietman, Thomas M} } @article {106, title = {Reduction of Coronavirus Burden With Mass Azithromycin Distribution.}, journal = {Clin Infect Dis}, volume = {71}, year = {2020}, month = {2020 11 19}, pages = {2282-2284}, abstract = {

We evaluated the potential antiviral effects of azithromycin on the nasopharyngeal virome of Nigerien children who had received multiple rounds of mass drug administration. We found that the respiratory burden of non-severe acute respiratory syndrome coronaviruses was decreased with azithromycin distributions. Clinical Trials Registration. NCT02047981.

}, keywords = {Administration, Oral, Antiviral Agents, Azithromycin, Child, Preschool, Coronavirus, Coronavirus Infections, Humans, Infant, Infant, Newborn, Mass Drug Administration, Nasopharynx, Nigeria, Viral Load}, issn = {1537-6591}, doi = {10.1093/cid/ciaa606}, author = {Doan, Thuy and Hinterwirth, Armin and Arzika, Ahmed M and Worden, Lee and Chen, Cindi and Zhong, Lina and Oldenburg, Catherine E and Keenan, Jeremy D and Lietman, Thomas M} } @article {221, title = {Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.}, journal = {Open Forum Infect Dis}, volume = {5}, year = {2018}, month = {2018 Aug}, pages = {ofy182}, abstract = {

Background: Mass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community{\textquoteright}s gut microbiome at 6 months after the last distribution.

Methods: In this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson{\textquoteright}s α diversity.

Results: In the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, \< .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson{\textquoteright}s index, = .005).

Conclusions: Two mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.

Clinical Trials Registration: NCT02048007.

}, issn = {2328-8957}, doi = {10.1093/ofid/ofy182}, author = {Doan, Thuy and Hinterwirth, Armin and Arzika, Ahmed M and Cotter, Sun Y and Ray, Kathryn J and O{\textquoteright}Brien, Kieran S and Zhong, Lina and Chow, Eric D and Zhou, Zhaoxia and Cummings, Susie L and Fry, Dionna and Oldenburg, Catherine E and Worden, Lee and Porco, Travis C and Keenan, Jeremy D and Lietman, Thomas M} }