BACKGROUND-Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis.

BackgroundInflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.ResultsIgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.ConclusionUsing IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0604-3) contains supplementary material, which is available to authorized users.

Objectives:The incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing worldwide. We used population-based health administrative data to determine national Canadian IBD incidence, prevalence, and trends over time of childhood-onset IBD.Methods:We identified children <16 years (y) diagnosed with IBD 1999–2010 from health administrative data in five provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec), comprising 79.2% of the Canadian population. Standardized incidence and prevalence were calculated per 100,000 children. Annual percentage change (APC) in incidence and prevalence were determined using Poisson regression analysis. Provincial estimates were meta-analyzed using random-effects models to produce national estimates.Results:5,214 incident cases were diagnosed during the study period (3,462 Crohn’s disease, 1,382 ulcerative colitis, 279 type unclassifiable). The incidence in Canada was 9.68 (95% CI 9.11 to 10.25) per 100,000 children. Incidence was similar amongst most provinces, but higher in Nova Scotia. APC in incidence did not significantly change over the study period in the overall cohort (+2.06%, 95% CI −0.64% to +4.76%). However, incidence significantly increased in children aged 0–5y (+7.19%, 95% +2.82% to +11.56%). Prevalence at the end of the study period in Canada was 38.25 (95% CI 35.78 to 40.73) per 100,000 children. Prevalence increased significantly over time, APC +4.56% (95% CI +3.71% to +5.42%).Conclusions:Canada has amongst the highest incidence of childhood-onset IBD in the world. Prevalence significantly increased over time. Incidence was not statistically changed with the exception of a rapid increase in incidence in the youngest group of children.

These findings suggest an underlying defect in the UC-afflicted intestinal tract even in the absence of inflammation, implicating barrier and microbial changes as primary abnormalities in UC that may play a causative role in disease development.

Definitive clinical trials of new chemotherapies for tuberculosis (TB) treatment require following subjects until at least six months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. In this study we prospectively assessed radiographic changes using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at two months and six months (CT only) in a cohort of subjects with multidrug-resistant (MDR) TB who were treated with second-line TB therapy for two years and then followed for an additional six months. CT scans were read semi-quantitatively by radiologists and computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at six months assessed by readers were predictive of outcomes but not two months and changes in computed abnormal volumes were predictive at both time points. Quantitative changes in FDG uptake two months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging biomarkers as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.

Background French Bulldogs develop a form of granulomatous colitis (GC) with histopathological resemblance to GC of Boxer dogs (GCB). GCB is associated with mucosally invasive Escherichia coli whose eradication correlates with clinical remission. Hypothesis/Objectives To characterize the clinical and histopathological features, presence or absence of invasive colonic bacteria, and response to fluoroquinolones in French Bulldogs with GC. Animals A total of 6 French Bulldogs with a histological diagnosis of GC. Methods Retrospective study of medical records. Bacterial colonization was evaluated using 16S rRNA probes for eubacteria and E. coli. Biopsy specimens from 3 dogs were cultured for bacteria. Clinical response to fluoroquinolone antimicrobials was determined. Results All dogs were ≤1 year of age with hematochezia that was refractory to empirical therapy. Clinicopathologic and fecal analysis did not reveal abnormalities. Abdominal ultrasound revealed patchy thickening of the colon in 4/5 dogs and regional lymphadenopathy in 5/5. Colonoscopic abnormalities included irregularly thickened and ulcerated mucosa, hyperemia, and overt bleeding in 4/6 cases. Multifocal accumulations of PAS‐positive macrophages and intramucosal E. coli were present in colonic biopsies of all 6 dogs. Administration of enrofloxacin (5/6) or marbofloxacin (1/6) at 4.4–10 mg/kg (median 10 mg/kg) PO q24h for 6–10 weeks was associated with clinical improvement within 5–14 days. All dogs remained in remission over a 3–30 month follow‐up period. Conclusions Granulomatous colitis in young French Bulldogs is associated with the presence of invasive E. coli and closely parallels GCB. Treatment with fluoroquinolone antimicrobials can induce lasting clinical remission.

BackgroundDiabetes mellitus is a risk factor for tuberculosis (TB) disease. There is evidence that diabetes also influences TB severity and treatment outcomes but information is incomplete and some published results have been inconsistent.MethodsA longitudinal cohort study was conducted at the National Masan Tuberculosis Hospital in the Republic of Korea. Subjects presenting with a first episode of TB or for retreatment of TB were followed from enrollment through completion of treatment. Demographic, clinical, and microbiological variables were recorded, along with assessment of outcomes. Results were compared in TB patients with and without diabetes or smoking history. Data were adjusted for gender, age, cohort, educational level and alcohol consumption.ResultsThe combined cohorts comprised 657 subjects. Diabetes was present in 25% and was associated with greater radiographic severity and with recurrent or relapsed TB. Diabetes and cigarette smoking independently increased the risk of death in the first 12 months after enrollment. Estimating the combined impact of diabetes and smoking yielded a hazard ratio of 5.78. Only 20% of diabetic subjects were non-smokers; 54% smoked ≥1 pack daily. In this cohort, the impact of diabetes on mortality was greater in patients younger than 50 years, compared to older patients.ConclusionsIn this cohort of Korean patients, diabetes exacerbated the severity of TB disease. Diabetic subjects who smoked ≥1 pack of cigarettes daily were at particularly high risk of death from TB. Strategies to improve TB outcomes could productively focus resources for patient education and TB prevention on the vulnerable population of younger diabetics, particularly those who also smoke.

Canada has among the highest rates of childhood-onset IBD in the world. Over 7000 children and youth under 18 years old are living with IBD in Canada, and 600 to 650 children under 16 years old are diagnosed annually. While the peak age of onset of IBD is highest in the second and third decades of life, over the past two decades incidence has risen most rapidly in children under 5 years old. The treatment of children with IBD presents important challenges including therapeutic choices, risk of adverse events to medications, psychosocial impact on the child and family, increased cost of health care and the implications of the transition from pediatric to adult care. Despite the unique circumstances faced by children and their families, there is a lack of research to help understand the causes of the rising incidence and the best therapies for children with IBD. Scientific evidence—and specifically clinical trials of pharmaceuticals—are too often extrapolated from adult research. Health care providers must strive to understand the unique impact of childhood-onset IBD on patients and families, while researchers must expand work to address the important needs of this growing patient population. Highlights In 2018, there are over 7000 children and youth under 18 years old living with IBD in Canada, and 600 to 650 young children (under 16 years) diagnosed every year. The number of children in Canada living with IBD is growing rapidly, increasing 50% in the first decade of the 21st century. Inflammatory bowel disease is still rare in children younger than 5 years of age, but it is occurring in such young children more often than in the past. Children with IBD are different from adults. For example, delayed growth, extent of disease and difficulties encountered during adolescence are all unique to the pediatric experience. We must consider the psychosocial well-being of both children and their families, given that caring for a child with IBD can affect the global functioning of families. Treatment approaches in children sometimes differ from those in adults. However, to date, all effective therapies in adults have also been effective in children. There is great need for clinical trials of new therapies in children so that they have equal access to emerging treatments and optimal pediatric dosing can be established. Key Summary Points Rates of new diagnoses in children under 16 years old were increasing most rapidly in Ontario (increased 5.8% per year) and Quebec (increased 2.8% per year). Nova Scotia has the highest rate of pediatric IBD, with lower rates in Quebec and Ontario. However, even Ontario and Quebec have higher rates of pediatric IBD than most countries in the world. Inflammatory bowel disease is caused by the interaction between genes, environmental risk factors, the microbiome and t...