Abstract

Staphylococcus aureus infections associated with implanted medical devices are difficult to treat and require long-lasting antibiotic therapies, especially when device removal is not possible or easy such as in the case of joint prostheses. Biofilm formation is a major cause of treatment failure and infection recurrence. This study aimed to test, for the first time, the in vitro combination of tedizolid plus rifampicin on methicillin-sensitive (MSSA ATCC 6538) and methicillin-resistant (MRSA ATCC 43300) S. aureus mature biofilm. Here, we demonstrated that the combination of tedizolid with rifampicin significantly disaggregated pre-formed biofilm of both strains, reduced their metabolic activity and exerted bactericidal activity at clinically meaningful concentrations. Notably, tedizolid was able to completely prevent the emergence of resistance to rifampicin. Moreover these effects were similar to those obtained with daptomycin plus rifampicin, a well-known and widely used combination. Preliminary results on some MRSA clinical isolates confirmed the efficacy of this combination in reducing biofilm biomass and preventing rifampicin resistance onset. Further in vivo studies are needed to confirm the validity of this promising therapeutic option that can be useful against biofilm-associated S. aureus infections.

Highlights

  • Staphylococcus aureus is one of most frequently encountered bacterial species forming biofilms on medical devices, such as venous central or peripheral catheters, bladder catheters, and joint and valve prostheses

  • The strains were found to be susceptible to tedizolid and daptomycin and both these drugs had the same minimal inhibitory concentrations (MICs) of 0.25 mg/L

  • ATCC reference strains and methicillin-resistant S. aureus (MRSA) clinical isolates were all susceptible to tedizolid, rifampicin and daptomycin (EUCAST, 2019)

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Summary

Introduction

Staphylococcus aureus is one of most frequently encountered bacterial species forming biofilms on medical devices, such as venous central or peripheral catheters, bladder catheters, and joint and valve prostheses. It causes difficult to treat infections especially when it is not possible, or not easy, to remove the device, such as in the case of joint or heart valves prostheses (Figueiredo et al, 2017). S. aureus is the most frequent pathogen responsible for early-onset infections that occur 12 months after surgery) are generally the result of bloodstream dissemination. In all these cases, antibiotic therapy exerts

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