Post-antibiotic Ocular Surface Microbiome in Children: A Cluster-Randomized Trial.
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ABSTRACT:
SUBMITTER: Doan T
PROVIDER: S-EPMC7384962 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Post-antibiotic Ocular Surface Microbiome in Children: A Cluster-Randomized Trial.
Doan Thuy T Hinterwirth Armin A Worden Lee L Arzika Ahmed M AM Maliki Ramatou R Chen Cindi C Zhong Lina L Zhou Zhaoxia Z Acharya Nisha R NR Porco Travis C TC Keenan Jeremy D JD Lietman Thomas M TM
Ophthalmology 20200220 8
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Project description:BackgroundAntibiotic-resistant infections have become a public health crisis that is driven by the inappropriate use of antibiotics. In the USA, antibiotic stewardship programs (ASP) have been established and are required by regulatory agencies to help combat the problem of antibiotic resistance. Post-operative antibiotic use in surgical cases deemed low-risk for infection is an area with significant overuse of antibiotics in children. Consensus among leading public health organizations has led to guidelines eliminating post-operative antibiotics in low-risk surgeries. However, the best strategies to de-implement these inappropriate antibiotics in this setting are unknown.Methods/designA 3-year stepped wedge cluster randomized trial will be conducted at nine US Children's Hospitals to assess the impact of two de-implementation strategies, order set change and facilitation training, on inappropriate post-operative antibiotic prescribing in low risk (i.e., clean and clean-contaminated) surgical cases. The facilitation training will amplify order set changes and will involve a 2-day workshop with antibiotic stewardship teams. This training will be led by an implementation scientist expert (VRM) and a pediatric infectious diseases physician with antibiotic stewardship expertise (JGN). The primary clinical outcome will be the percentage of surgical cases receiving unnecessary post-operative antibiotics. Secondary clinical outcomes will include the rate of surgical site infections and the rate of Clostridioides difficile infections, a common negative consequence of antibiotic use. Monthly semi-structured interviews at each hospital will assess the implementation process of the two strategies. The primary implementation outcome is penetration, which will be defined as the number of order sets changed or developed by each hospital during the study. Additional implementation outcomes will include the ASP team members' assessment of the acceptability, appropriateness, and feasibility of each strategy while they are being implemented.DiscussionThis study will provide important information on the impact of two potential strategies to de-implement unnecessary post-operative antibiotic use in children while assessing important clinical outcomes. As more unnecessary medical practices are identified, de-implementation strategies, including facilitation, need to be rigorously evaluated. Along with this study, other rigorously designed studies evaluating additional strategies are needed to further advance the burgeoning field of de-implementation.Trial registrationNCT04366440. Registered April 28, 2020, https://clinicaltrials.gov/ct2/show/NCT04366440 .
| S-EPMC7980649 | biostudies-literature
Project description:PurposeCarboxymethylcellulose is an artificial tear ingredient known to decrease gut microbiome diversity when ingested. This study examines the effect of carboxymethylcellulose on ocular surface microbiome diversity and composition.MethodsHealthy adult participants without significant ophthalmic disease or concurrent carboxymethylcellulose artificial tear use were allocated randomly to take carboxymethylcellulose or control polyethylene glycol artificial tears for seven days. Conjunctival swabs were collected before and after artificial tear treatment. This trial is registered at clinicaltrials.gov (NCT05292755). Primary outcomes included abundance of bacterial taxa and microbiome diversity as measured by the Chao-1 richness estimate, Shannon's phylogenetic diversity index, and UniFrac analysis. Secondary outcomes included Ocular Surface Disease Index scores and artificial tear compliance.ResultsOf the 80 enrolled participants, 66 completed the trial. Neither intervention affected Chao-1 richness (analysis of variance [ANOVA], P = 0.231) or Shannon's diversity index (ANOVA, P = 0.224). Microbiome samples did not separate by time point (permutation multivariate analysis of variance [PERMANOVA], P = 0.223) or intervention group (PERMANOVA, P = 0.668). LEfSe taxonomic analysis revealed that carboxymethylcellulose depleted several taxa including Bacteroides and Lachnoclostridium, but enriched Enterobacteriaceae, Citrobacter, and Gordonia. Both interventions decreased OSDI scores (Wilcoxon signed rank test, P < 0.05), but there was no significant difference between interventions (Mann-Whitney U, P = 0.54).ConclusionsCarboxymethylcellulose artificial tears increased Actinobacteriota but decreased Bacteroides and Firmicutes bacteria. Carboxymethylcellulose artificial tears do not affect ocular surface microbiome diversity and are not significantly more effective than polyethylene glycol artificial tears for dry eye treatment.Translational relevanceThe 16S microbiome analysis has revealed small changes in the ocular surface microbiome associated with artificial tear use.
| S-EPMC10424155 | biostudies-literature
Project description:PurposeThere is growing evidence for a critical role of the microbiome in ocular health and disease. We performed a prospective, observational study to characterize the ocular surface microbiome (OSM) in four chronic ocular surface diseases (OSDs) and healthy controls.MethodsSterile swabs were used to collect samples from each eye of 39 patients (78 eyes). Sterile technique and multiple controls were used to assess contamination during DNA extraction, amplification and sequencing. Concurrent use of topical antibiotics, steroids, and bandage contact lenses (BCLs) was documented.ResultsDespite the low biomass of the ocular surface, 47/78 (60%) eyes sampled had positive sequencing reads. We observed that half of patients (8/17, 47%) had distinct microbiomes in each eye. Healthy controls had a Lactobacillus/Streptococcus mixture or significant Corynebacterium. Staphylococcus predominated in 4/7 (57%) patients with Stevens-Johnson Syndrome (SJS) in at least one eye, compared to 0/10 healthy controls. Interestingly, 8/11 (73%) eyes with SJS were using BCLs, including 4/5 (80%) eyes dominated by Staphylococcus. Lax eyelid syndrome (LES) and Dry Eye Disease (DED) patients had similar OSMs, with Corynebacterium being the most prevalent bacteria. Alpha diversity was higher in controls and ocular graft-vs-host (oGVHD) patients compared to the other OSDs.ConclusionsOnly 50% of the 39 patients had similar microbiomes in each eye. A majority of healthy eyes had a Lactobacillus/Streptococcus mix or Corynebacterium microbiome. Staphylococcus predominated in SJS, Lactobacillus in oGVHD, and Corynebacterium in DED and LES. There may be an association between different OSDs and the microbiome.
| S-EPMC7905829 | biostudies-literature
Project description:In human medicine, antibiotics have been widely used to treat microbial infections. The extensive use of antibiotics is a leading cause of antibiotic resistance. Currently, the influence of the use of antibiotics on the ocular surface microbiome in the course of keratitis treatment remains to be explored in depth. We performed metagenomic analyses in a cohort of 26 healthy controls (HCs), 28 keratitis patients (KPs) who received antibiotics [KP (abx+) group], and 12 KPs who were antibiotic naive [KP (abx-) group]. We identified that the dissimilarities in microbial community structure (Bray-Curtis and Jaccard analyses) between the KP (abx+) group and the HC group were greater than those between the KP (abx-) group and the HC group. Pseudomonas lactis, P. aeruginosa, Pseudomonas sp. FDAARGOS_380, Pseudomonas sp. J380, Corynebacterium simulans, Streptococcus pyogenes, Finegoldia magna, and Aspergillus oryzae had no statistically significant differences between the KP (abx+) and KP (abx-) groups but did have statistically significant differences between the KP (abx+) and HC groups and between the KP (abx-) and HC groups. Among them, Pseudomonas lactis, P. aeruginosa, Pseudomonas sp. FDAARGOS_380, and Pseudomonas sp. J380 were identified as possible hosts carrying multidrug-resistant genes. The total abundance and number of antibiotic resistance genes (ARGs) were greater in the KP (abx+) group than in the HC and KP (abx-) groups. The functional profile analysis of ocular surface microbiota revealed that pathogenesis-related functional pathways and virulence functions were enriched in KPs. In conclusion, our results show that empirical antibiotic treatment in KPs leads to increases in the antibiotic resistance of ocular surface microbiota. IMPORTANCE Treatment for keratitis is based on appropriate antimicrobial therapy. A direct correlation between antibiotic use and the extent of antibiotic resistance has been reported. Therefore, knowledge of the antibiotic resistance patterns of ocular surface microbial flora in KPs is important for clinical treatment. To the best of our knowledge, this is the first study to use metagenomic approaches to investigate the associations between ophthalmic antibiotic use and the ocular surface microbiome of KPs. Monitoring the microbiota and antibiotic resistome profiles for the ocular surface has huge potential to help ophthalmologists choose the appropriate antibiotics and will thereby improve the efficacy of treatment regimens, which has important implications for reducing the development of antibiotic resistance of the ocular surface to a certain extent.
| S-EPMC9045205 | biostudies-literature
Project description:PurposeTo perform a pilot study to characterize the effect of clinical parameters on the ocular surface microbiome (OSM) in children and adults using 16s ribosomal RNA sequencing.MethodsProspective, cross-sectional study using 16s sequencing to evaluate the OSM. Comparisons were made in bacterial composition by 1) age, 2) gender, 3) sampling location of the ocular and periocular surfaces, and 4) topical drop use. 16s sequencing was performed using Illumina MiSeq 250 and analyzed using Qiime.ResultsThirty patients (15 children [mean 3.7 years], 15 adults [mean 60.4 years]) were sampled. Both principal coordinate analysis and unifrac distance analysis showed significant differences in the composition between the pediatric and adult OSMs (both p=0.001). The eyelid margin microbiota did not show any distinct clustering compared to conjunctiva within the pediatric samples but tended to show a distinction between anatomic sites in adult samples. No differences in OSM were noted by topical drop use.Conclusion16s sequencing is a useful tool in evaluating the OSM in patients of all ages, showing a distinct difference between pediatric and adult microbiomes.
| S-EPMC6040630 | biostudies-literature
Project description:PurposeUnlike other microbiomes of the body, the composition of the ocular surface microbiome (OSM) in children has yet to be thoroughly explored. Our goal was to evaluate the OSM in young infants and compare its composition to older children using both culture dependent and independent methodologies to assess for differences with age.MethodsProspective, observational, cross-sectional study of children <18 years of age at a university-based institution. The mucosal surfaces of both eyes, nose and throat were swabbed with a forensic-quality swab. Half of the swab was plated for culture and the other half underwent 16S sequencing. Culture results and microbiome diversity were analyzed.ResultsFifty patients (mean age 37 months, range 1-168 months) were enrolled. Forty-seven eyes of 30 patients had positive cultures; four eyes grew >1 species. Culture positive patients were older (43 vs. 29 months, P = 0.19). Additionally, older children had greater diversity than children under 6 months of age by 16S sequencing (P = 0.05). Staphylococcus species were predominant by culture (35/52 isolates) and by 16S sequencing. The OSM was fairly similar to the nose microbiome, whereas the throat microbiome differed significantly and had a higher abundance of Streptococcaceae (P = 0.001).ConclusionsThe OSM is predominantly composed of Staphylococcus species in children, as demonstrated by both culture dependent and culture independent methods. Older children were more likely to have growth on culture and have more a complex bacterial milieu with 16S sequencing.Translational relevance16S sequencing provides more robust information regarding the composition of the microbiomes than culture dependent methods.
| S-EPMC6269136 | biostudies-literature
Project description:This cross-sectional, age- and gender-matched study included 20 eyes of non-diabetic subjects (non-DM group) and 60 eyes of type 2 diabetes mellitus (DM group). Subgroups of DM were classified by diabetic retinopathy (DR) staging into no DR (DM-no DR), non-proliferative DR (DM-NPDR), proliferative DR (DM-PDR), and by glycemic control (well-controlled DM; HbA1c < 7%, poorly controlled DM; HbA1c ≥ 7%). Conjunctival swabs were performed for ocular surface microbiome analysis using conventional culture and next-generation sequencing analysis (NGS). A higher culture-positive rate was found in DM (15%) than in non-DM group (5%) (p value = 0.437). Pathogenic organisms and antibiotic-resistant strains were detected in the DR groups (DM-NPDR and DM-PDR). The NGS analysis showed that potentially pathogenic bacteria such as Enterobacteriaceae, Neisseriaceae, Escherichia-Shigella, and Pseudomonas predominated in DM, especially in DR. There was dissimilarity in the ocular surface microbiome between DM and non-DM groups. The subgroup analysis showed that the DR group had significantly different microbial community from DM-no DR and non-DM groups (p value < 0.05). The microbial community in the poorly controlled DM was also significantly different from well-controlled DM and non-DM groups (p < 0.001). Using the NGS method, our study is the first to signify the importance of DR and glycemic control status, which affect the changes in the ocular surface microbiome.
| S-EPMC9747965 | biostudies-literature
Project description:The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.
| S-EPMC3139980 | biostudies-literature
Project description:Ocular surface microbiome in dupilumab associated ocular surface disease
| PRJEB57775 | ENA
Project description:BackgroundMass 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's gut microbiome at 6 months after the last distribution.MethodsIn 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's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo 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 registrationNCT02048007.
| S-EPMC6101535 | biostudies-literature