Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early <i>erm</i>B Gene Expression, Metabolic Activity and Growth of an <i>erm</i>(B)-Expressing Macrolide-Resistant Strain of <i>Streptococcus pneumoniae</i>

Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.

Tailoring lifestyle programmes for diabetes prevention for US South Asians

Objective The purpose of this study was to develop and test the feasibility of a culturally tailored Diabetes Prevention Programme(DPP)for US South Asians,a large population with high diabetes risk.Design The South Asian Health and Prevention Education(SHAPE)study included:(1)focus group discussions with South Asian adults to understand views of lifestyle behaviours and diabetes prevention;(2)modification of the US DPP for South Asians and(3)a pilot,pre-post study to test the feasibility and impact of delivering the culturally tailored programme.Setting The study was conducted in Atlanta,Georgia,USA.Focus group discussions and intervention classes were held at locations within the community(eg,South Asian restaurants,a public library,university classrooms,a South Asian owned physical therapy studio).Participants The focus group discussions(n=17 with 109 individuals)included adults aged 25 years of older who self-identified as South Asian.Groups were stratified by age(25-40 years or older than 40 years)and sex.The SHAPE pilot study included 17(76.5%male with a mean age of 46.9±12 years)South Asian adults aged 25 years or older with pre-diabetes and body mass index(BMI)>22 kg/m2.results Formative data from 17 focus group discussions and a community board guided the modification of the DPP curriculum to reflect cultural food preferences and include tools to leverage social support,create a stronger foundation in exercise and overcome culturally specific barriers.The SHAPE pilot study included 17 South Asian adults with pre-diabetes and BMI>22 kg/m2.There were positive changes in participants’weight,waist circumference,blood pressure,plasma lipids,HbA1c and other cardiometabolic markers postintervention and 55%of participants regressed to normoglycaemia.Conclusion These results provide important information on the barriers faced by US South Asians in participating in‘standard’lifestyle change programs,indicate the feasibility of culturally tailored programmes and show positive impact of a culturally tailored programme for diabetes prevention in the South Asian population.