RESUMO
Disinfection in the hospital environment remains challenging, especially for wide and structurally complex objects such as beds or wheelchairs. Indeed, the regular disinfection of these objects with chemicals is manually carried out by healthcare workers and is fastidious and time-consuming. Alternative antibacterial techniques were thus proposed in the past decades, including the use of naturally antimicrobial UVC. Here, the antibacterial efficiency of a large UVC box built to accommodate wheelchairs was investigated through testing bacterial burden reductions on various parts of a wheelchair, with various support types and with several treatment durations. The results demonstrate a time-dependent antibacterial effect, with a strong burden reduction at only five minutes of treatment (>3-log median reduction in Escherichia coli and Staphylococcus epidermidis). The UVC flux and residual bacterial burden both significantly varied depending on the spatial location on the wheelchair. However, the nature of the support impacted the antibacterial efficiency even more, with residual bacterial burdens being the lowest on rigid materials (steel, plastics) and being the highest on tissue. On metallic samples, the nature of the alloy and surface treatment had various impacts on the antibacterial efficiency of the UVC. This study highlights the efficiency of the tested UVC box to efficiently and quickly decontaminate complex objects such as wheelchairs, but also gives rise to the warning to focus on rigid materials and avoid porous materials in the conception of objects, so as to ensure the efficiency of UVC decontamination.
RESUMO
OBJECTIVES: Iclaprim is a novel 2,4-diaminopyrimidine that exhibits potent, rapid bactericidal activity against major Gram-positive pathogens, including methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus, and is currently in clinical development for the treatment of complicated skin and skin structure infections. An understanding of the known mechanism of resistance to trimethoprim led to the design of this new inhibitor, with improved affinity towards dihydrofolate reductase (DHFR) from S. aureus and clinically useful activity against S. aureus including isolates resistant to trimethoprim. The objective of this study was to characterize the mode of action of iclaprim and its inhibitory properties against DHFR. METHODS: The mode of action of iclaprim was assessed by enzymatic analysis, direct binding studies, macromolecular synthesis profiles, synergy and antagonism studies to define its role as an inhibitor of DHFR. The binding properties of iclaprim to DHFR were compared with those of trimethoprim by X-ray crystallography. RESULTS: The enzymatic properties, direct binding and X-ray crystallographic studies delineated the mode of interaction with DHFR and the reason for the increased affinity of iclaprim towards the enzyme. The effect of iclaprim on bacterial physiology suggests that iclaprim behaves as a classical antibacterial DHFR inhibitor, as previously documented for trimethoprim. CONCLUSIONS: Iclaprim binds and inhibits bacterial DHFR in a similar manner to trimethoprim. However, the increased hydrophobic interactions between iclaprim and DHFR account for increased affinity and, unlike trimethoprim, enable iclaprim to inhibit even the resistant enzyme with nanomolar affinity, thus overcoming the mechanism of trimethoprim resistance. The increased antibacterial activity and lower propensity for resistance make iclaprim a clinically promising and useful inhibitor.
Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Pirimidinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Tetra-Hidrofolato Desidrogenase/metabolismo , Antibacterianos/metabolismo , Cristalografia por Raios X , Inibidores Enzimáticos/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Pirimidinas/metabolismo , Trimetoprima/metabolismo , Trimetoprima/farmacologiaRESUMO
In this paper, we report the successful combination of macroscopic uniaxial tensile testing of bulk specimen combined with In situ dislocation-scale observations of the evolution of deformation microstructures during loading at several stress states. The dislocation-scale observations were performed by Accurate Electron Channeling Contrast Imaging in order to follow the defects evolution and their interactions with grain boundaries for several regions of interest during macroscopic loading. With this novel in situ procedure, the slip systems governing the deformation in polycrystalline bulk ß-Ti21S are tracked during the macroscopic uniaxial tensile test. For instance, curved slip lines that are associated with "pencil glide" phenomenon and tangled dislocation networks are evidenced.