Hypervirulent Clostridium difficile PCR-Ribotypes Exhibit Resistance to Widely Used Disinfectants

The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon®, Newgenn®, Proceine 40® and Hibiscrub®. Whereas, for Steri7® and Biocleanse® the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe® was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR-ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings

Can better prescribing turn the tide of resistance?

In the wake of concerns about the level of antibiotic resistance, governments worldwide are pressing for reduced antibiotic use, hoping thereby to reverse resistance trends. Is success likely? The evidence is mixed, and expectations should be tempered by the growing realization that many resistant bacteria are biologically fit, making them difficult to displace. If resistance is unlikely to be reduced significantly by changing prescription practices, how can clinicians outpace increased resistance, particularly when much of 'big pharma' is abandoning antibiotic development

Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with incorporation of MAPK signals in Smad1

Alterations in the signaling pathways of bone morphogenetic proteins (BMPs) and activation of the ERK/MAP kinase (MAPK) pathway by growth factors have been implicated in the development and progression of prostate cancer. Smad1 acts as a substrate for MAPKs and also performs a central role in transmitting signals from BMPs. We found that BMPs/Smad1 signaling inhibits the growth of androgen-sensitive prostate cancer cells. Upon the incorporation of ERK/MAPK signals at its linker region, Smad1 physically interacts with androgen-activated androgen receptor (AR) and suppresses its functions. BMPs induce the function of Smad1 as an AR transcriptional corepressor. We demonstrated in vivo that Smad1 signaling is low in androgen-regulated growth of prostate cancer, is activated after castration, and also is decreased in hormone-independent tumors. The activation status of ERK/MAPK parallels Smad1 in the progression of prostate cancer; thus, our findings indicate a molecular basis for the integration of signals of MAPK and Smad1 in the progression and androgen regulation of prostate cancer