Newin vitroandin vivomodels to evaluate antibiotic efficacy inStaphylococcus aureusprosthetic vascular graft infection

Abstract

Despite the heterogeneity of results according to bacterial strains, these innovative models represent an option to better evaluate the in vitro efficacy of antibiotics on Dacron(®)-related biofilm S. aureus infections, and to screen different antibiotic regimens in a mouse model of PVGIs.

New Insight into Daptomycin Bioavailability and Localization in Staphylococcus aureus Biofilms by Dynamic Fluorescence Imaging

“…In conclusion, consistently with the previous in vivo study aiming at evaluating the antibiotic efficacy in S. aureus prosthetic vascular graft infections (18), we demonstrated in the present in vitro model a strain-dependent lack of daptomycin activity toward biofilms. Dynamic fluorescence microscopy allowed discarding a lack of antibiotic availability and interaction with bacteria.…”

“…Two distinctive findings in this study concern the BCB8 clinical isolate, which discriminated itself by a twofold-higher penetration coefficient compared to the other strains tested and a greater susceptibility as revealed by the observation of a larger proportion of dead cells over the whole biofilm thickness, including the basal layer in contact with the substratum. These results are in line with those obtained in vivo (18), which demonstrated a strain-dependent activity of daptomycin against S. aureus biofilms. In view of the antibiotic mechanism of action which is supposed to target the plasma membrane, the observed variable response depending on the bacterial strain may be due to a change in membrane composition or conformation from a strain to another.…”

“…In this context, the ambivalence of the published results on daptomycin activity is a relevant example. Despite increasing data about daptomycin as an option to treat implant-associated S. aureus infections, as many failures (18,27) as successes (7-9, 12) have been reported both in clinical practice and in laboratory models. This highlights that S. aureus BAI resistance/tolerance mechanisms to antimicrobials deserve more attention.…”

“…To obtain a realistic representation of daptomycin action against S. aureus biofilms, we developed an in vitro model built on the basis of our recently published in vivo study on S. aureus prosthetic vascular graft infections using the same strains (18). The interest of this approach was the possibility to use fluorescence imaging techniques that cannot be employed in vivo (confocal laser scanning microscopy [CLSM], time-lapse microscopy, and fluorescence recovery after photobleaching [FRAP]) to examine the penetration, diffusion, bioavailability, and localization of the fluorescently labeled antibiotic inside the biofilms.…”

“…To validate this approach, we monitored for 72 h the activity of daptomycin against biofilms formed by methicillin-susceptible and methicillin-resistant clinical and collection strains. In addition, we enriched the culture medium with proteins and calcium to mimic the in vivo physiological conditions of our mouse model (18). The same experiments were performed in the presence of rifampin, an antibiotic that can be combined with daptomycin for recalcitrant S. aureus BAI.…”