Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature

KIAA2022 is an X‐linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19‐years‐old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café‐au‐lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10‐years‐old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café‐au‐lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.     

Preliminary study on the protective effect of vitamin C on monosodium glutamate-induced hepatotoxicity in rats

Monosodium glutamate (MSG) is a food additive with a wide range of biological effects but its high dose and prolonged use can cause a toxic effect on the liver. Therefore, the present study was aimed at investigating the role of vitamin C in MSG-induced hepatotoxicity in rats. MSG was administered to rats (by gavage) at a dose of 6 mg/g body weight for 10 days to induce hepatotoxicity, and vitamin C at a dose of 500 mg/kg body weight was coadministered to evaluate its ameliorating effect by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum; superoxide dismutase (SOD) and catalase activities in liver fraction; lipid peroxidation; and liver weight. It was found that MSG significantly (P?<?0.05) induced lipid peroxidation (LPO), increased liver weight, and increased activity of SOD and catalase in the liver of animals. The activity of ALT and AST was also increased in the serum on MSG administration. Vitamin C (500 mg/kg) coadministered with MSG significantly reduced LPO and liver weight and decreased the hepatic activity of catalase, but the activity of SOD was not reduced significantly. Also, a significant reduction in ALT and AST activity was observed. MSG induced oxidative stress and hepatic toxicity in the experimental animals at a dose of 6 mg/g body weight. Vitamin C significantly reduced the oxidative stress and hepatic toxicity induced by MSG, thereby providing a protective effect against the MSG-induced hepatotoxicity. The protective effect is associated with decreased LPO and liver weight and decreased activities of catalase, ALT, and AST.     

Accuracy of glycated haemoglobin in screening for pre‐diabetes in Asian Indians—a community survey: the Chandigarh Urban Diabetes Study (CUDS)

Aim To compare American Diabetes Association and International Expert Committee recommended cut‐off values of HbA_1c for detecting the presence of pre‐diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. Methods A cross‐sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA_1c was measured on a Bio‐Rad 10 system in 1972 subjects. Results Of the 1972 subjects studied, 329 were detected to have pre‐diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA_1c cut‐off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre‐diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA_1c cut‐off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA_1c cut‐offs underdiagnosed the presence of pre‐diabetes in 38 and 64% of these subjects, respectively. Conclusions The American Diabetes Association and the International Expert Committee recommended HbA_1c cut‐off values and oral glucose tolerance tests identify different pre‐diabetes cohorts. Long‐term prospective studies are required to define the usefulness of one over the other.