Impact of exposure of methicillin-resistant Staphylococcus aureus to polyhexanide in vitro and in vivo.

Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increase the need to develop alternative decolonization molecules. The absence of reported adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as topical antiseptic. In the present study we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced-susceptibility to polyhexanide by prolonged-stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes, and with concomitant decreased susceptibility to daptomycin and other cell-wall active antibiotics. However, the in vitro emergence of reduced-susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine antiseptic. During in vivo polyhexanide clinical decolonization treatment, neither polyhexanide reduced-susceptibility nor chlorhexidine cross-resistance were observed. Together, these observations suggest that polyhexanide could be used safely for decolonisation of carriers of chlorhexidine-resistant S. aureus strains but highlight the need for careful use of polyhexanide at low antiseptic concentrations

Nouvelles voies de synthèse stéréosélectives de monofluoroalcènes

Parmi les différentes fonctionnalités contenant un atome de fluor, les fluoroalcènes sont des motifs particulièrement intéressants, possédant de nombreuses applications dans le domaine de la chimie médicinale, des sciences des matériaux, et en synthèse organique. Pourtant, il existe peu de méthodes efficaces pour la synthèse stereoselective de ces molécules, et certaines classes de monofluoroalcènes sont encore difficiles d'accès avec les stratégies actuelles. Le sujet de cette thèse porte donc sur le développement de nouvelles voies de synthèse stéréosélectives de monofluoroalcènes diversement substitués. Les propriétés de l'atome de fluor, et leurs effets sur le profil pharmacologique de molécules bioactives (lipophilie, solubilité, stabilité métabolique, etc.), seront exposés dans le premier chapitre de cette thèse. Des travaux exploratoires sur la préparation d'alcynes fluorés seront ensuite présentés dans le chapitre 2 ; ils ont mené à la découverte de la réactivité particulière des β, β-difluorostyrènes silylés vis-à-vis de certains nucléophiles (organolithiens, hydrure). Les β, β-difluorostyrènes silylés ont alors pu être utilisés comme précurseurs communs pour la synthèse stereoselective de monofluoroalcènes tétrasubstitués (chapitre 3), trisubstitués (chapitre 4), et disubstitués (chapitre 5). Pour terminer, ces nouvelles méthodologies ont été appliquées à la synthèse de composés bioactifs (chapitres 3 et 4)

Tri- and difluoromethoxylated N-based heterocycles − Synthesis and insecticidal activity of novel F3CO- and F2HCO-analogues of Imidacloprid and Thiacloprid

International audienc

Considerations for de-escalating universal masking in healthcare centers

Three years after the beginning of the COVID-19 pandemic, better knowledge on the transmission of respiratory viral infections (RVI) including the contribution of asymptomatic infections encouraged most healthcare centers to implement universal masking. The evolution of the SARS-CoV-2 epidemiology and improved immunization of the population call for the infection and prevention control community to revisit the masking strategy in healthcare. In this narrative review, we consider factors for de-escalating universal masking in healthcare centers, addressing compliance with the mask policy, local epidemiology, the level of protection provided by medical face masks, the consequences of absenteeism and presenteeism, as well as logistics, costs, and ecological impact. Most current national and international guidelines for mask use are based on the level of community transmission of SARS-CoV-2. Actions are now required to refine future recommendations, such as establishing a list of the most relevant RVI to consider, implement reliable local RVI surveillance, and define thresholds for activating masking strategies. Considering the epidemiological context (measured via sentinel networks or wastewater analysis), and, if not available, considering a time period (winter season) may guide to three gradual levels of masking: (i) standard and transmission-based precautions and respiratory etiquette, (ii) systematic face mask wearing when in direct contact with patients, and (iii) universal masking. Cost-effectiveness analysis of the different strategies is warranted in the coming years. Masking is just one element to be considered along with other preventive measures such as staff and patient immunization, and efficient ventilation