Association between antibiotic exposure and adverse outcomes of children and pregnant women: evidence from an umbrella review

Background Antibiotics are widely prescribed among children and pregnant women,but their safety profile is controversial.This study aimed to summarize and appraise current evidence for the potential impact of antibiotic exposure on pregnancy outcomes and children’s health.Methods PubMed,Embase,Web of Science and the Cochrane Database of Systematic Reviews were searched from inception to June 2022.Meta-analyses of any study design comparing the impact of antibiotic exposure with nonexposure among children,pregnant women and prepregnant women on adverse health outcomes of children and pregnancy were retrieved.The quality of evidence was assessed by a Measurement Tool to Assess Systematic Reviews 2(AMSTAR2)and the Grading of Recommendations,Assessment,Development and Evaluation(GRADE).Data were reanalyzed,and the credibility of the evidence was determined.Results Out of 2956 studies identified,19 articles with 39 associations were included.Totally 19 of the associations(48.72%)were statistically significant with a P value≤0.05,while only six were supported by highly suggestive evidence.Children with postnatal antibiotic exposure had a higher risk of developing asthma odds ratio(OR):1.95,95%confidence interval(CI):1.76–2.17,wheezing(OR:1.81,95%CI 1.65–1.97)and allergic rhinoconjunctivitis(OR:1.66,95%CI 1.51–1.83),with prediction intervals excluding the nulls.Quality assessed by both AMSTAR2 and GRADE of included meta-analyses were very low in general.Conclusions Antibiotic exposure in early life was associated with children’s long-term health,especially in cases of allergic diseases.Prenatal exposure might also influence children’s health in some aspects but requires more high-quality evidence.Potential adverse effects of antibiotics on pregnancy outcomes were not observed in our study.Studies with higher quality and better quantification of antibiotic exposure are needed in the future.

The association between radiological spreading pattern and clinical outcomes in necrotizing external otitis

Objectives: Necrotizing external otitis(NEO) is a rare infectious disease of the skull base. The purpose of this study was to determine whether clinical outcomes of NEO can be correlated to different infectious spread patterns.Methods: Retrospective chart review from 2010 to 2019 with NEO patients, who were divided into two cohorts: single spreading patterns(group A) or complex spreading patterns(group B) as diagnosed by CT.Clinical symptoms, diagnostic and treatment delay, course of disease, complications, and duration of antibiotic exposure were retrospectively collected from patient records.Results: 41 NEO patients were included, of which 27 patients belonged to group A(66%). The diseaserelated mortality rate was 12.2% among the entire cohort, no differences were found between group A and B. Higher rates of N.VII(42.9% vs 14.8% P = 0.047) and N. IX palsies were found in group B compared to group A(28.6% vs 3.7%, P = 0.039). The median duration of antibiotic use was significantly different for a complex spreading pattern, clinical recovery and hospitalizations. Complications were associated with higher diagnostic delay and with a complex spread pattern. The median duration of follow-up was 12.0(IQR 6.0-19.5) months.Conclusion: NEO is a severe disease, with significant mortality and morbidity(cranial nerve palsies). The radiological spread pattern may assist in predicting clinical outcome. Furthermore, complex spread patterns are associated with higher rates of clinical nerve palsies(N. VII and N.IX), complications, surgery rates and longer duration of antibiotic use. Diagnostic delay was associated with mortality, complications and facial palsies.

Gut microbiota controls the development of chronic pancreatitis:A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota.Recently,accumulating evidence has supported a correlation between gut dysbiosis and CP development.However,whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear.Herein,an experimental CP was induced by repeated high-dose caerulein injections.The broad-spectrum antibiotics(ABX)and ABX targeting Gram-positive(G+)or Gram-negative bacteria(G-)were applied to explore the specific roles of these bacteria.Gut dysbiosis was observed in both mice and in CP patients,which was accompanied by a sharply reduced abundance for short-chain fatty acids(SCFAs)-producers,especially G+bacteria.Broad-spectrum ABX exacerbated the severity of CP,as evidenced by aggravated pancreatic fibrosis and gut dysbiosis,especially the depletion of SCFAs-producing G+bacteria.Additionally,depletion of SCFAs-producing G+bacteria rather than G-bacteria intensified CP progression independent of TLR4,which was attenuated by supplementation with exogenous SCFAs.Finally,SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching.The study supports a critical role for SCFAs-producing G+bacteria in CP.Therefore,modulation of dietary-derived SCFAs or G+SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Intestinal microbiota and juvenile idiopathic arthritis:current understanding and future prospective

Background Juvenile idiopathic arthritis(JIA)characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease,caused by both host genetic factors and environmental triggers.Recent evidence has mounted to focus on the intestinal microbiota,a potentially recognized set of environmental triggers affecting JIA development.Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA.Data sources We searched PubMed for animal and human studies publications with the search terms"intestinal microbiota or gut microbiota"and"juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis".Results Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis.Alternatively,a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization,including cesarean section,formula feeding,and antibiotic exposure.Aberrant intestinal microbiota may influence the development of JIA by mediating host immune programming and by altering mucosal permeability.Conclusions Specific microbial factors may contribute to the pathogenesis of JIA.Intensive studies,however,are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships.Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.