Abstract
The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections, always treated with vancomycin and daptomycin, has led to the emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA) and daptomycin non-susceptible (DNS) S. aureus. Even if glycopeptides and daptomycin remain the keystone for treatment of resistant S. aureus, the need for alternative therapies that target MRSA has now become imperative. The in vitro antibacterial and bactericidal activity of dalbavancin was evaluated against clinically relevant S. aureus showing raised antibiotic resistance levels, from methicillin-susceptible to Multidrug-Resistant (MDR) MRSA, including hVISA, DNS and rifampicin-resistant (RIF-R) strains. A total of 124 S. aureus strains were tested for dalbavancin susceptibility, by the broth microdilution method. Two VISA and 2 hVISA reference strains, as well as a vancomycin-resistant (VRSA) reference strain and a methicillin-susceptible Staphylococcus aureus (MSSA) reference strain, were included as controls. Time–kill curves were assayed to assess bactericidal activity. Dalbavancin demonstrated excellent in vitro antibacterial and bactericidal activity against all S. aureus resistance classes, including hVISA and DNS isolates. The RIF-R strains showed the highest percentage of isolates with non-susceptibility, reflecting the correlation between rpoB mutations and VISA/hVISA emergence. Our observations suggest that dalbavancin can be considered as an effective alternative for the management of severe MRSA infections also sustained by refractory phenotypes.
Highlights
Reduced susceptibility to glycopeptides in Staphylococcus aureus poses a great threat to antimicrobial chemotherapy worldwide, and in methicillin-resistant S. aureus (MRSA), it is seriously challenging to the therapeutic field
In only two cases we found non-susceptibility values: a hospital-associated HA-MRSA/VSSA strain belonging to the USA500-like (ST8-SCCmec IV) clone with a dalbavancin minimum inhibitory concentrations (MICs) value one dilution above the susceptibility breakpoint (MIC 0.25 mg/L), and a daptomycin non-susceptible S. aureus (DNS)/VISA
MICs in the 1–2 mg/L range, are increasingly being reported and a systematic review of the literature on hVISA reported that patients infected with these organisms had a 2.37-fold greater failure rate compared to those infected with fully susceptible (VSSA) organisms [19]
Summary
Reduced susceptibility to glycopeptides in Staphylococcus aureus poses a great threat to antimicrobial chemotherapy worldwide, and in methicillin-resistant S. aureus (MRSA), it is seriously challenging to the therapeutic field. Vancomycin-intermediate S. aureus strains with homogeneous (VISA) or heterogeneous (hVISA) phenotypes are increasingly being reported all over the world, exposing significant controversies on the present and future role of vancomycin and teicoplanin in the treatment of severe infections sustained by hVISA-MRSA isolates [1]. In these strains, often with vancomycin minimum inhibitory concentrations (MICs) in the 1–2 mg/L range, this reduced susceptibility has been attributed to various cell-wall abnormalities, evolving in a multistep fashion. Infections sustained by daptomycin non-susceptible S. aureus (DNS) and DNS-VISA phenotypes, even if rare, are increasingly associated with increased higher mortality and morbidity rates [3]
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