In Vitro Activity of Dalbavancin against Refractory Multidrug-Resistant (MDR) Staphylococcus aureus Isolates

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.

Cell wall thickness and the molecular mechanism of heterogeneous vancomycin‐intermediateStaphylococcus aureus

“…Cell wall thickness hVISA is rare in the clinic and the mechanism underlying the reduced sensitivity to VAN of this strain has not been elucidated (Bongiorno et al 2020). The hVISA strain investigated in this study was derived from a patient in our hospital and the patient who had not exposed to VAN before.…”

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

“…It is widely used for the treatment of skin and soft tissue infections. 97 In vivo and in vitro studies have shown that dalbavancin has antimicrobial activity against GPB, including MRSA, MSSA, coagulase-negative staphylococci (CoNS), and Streptococcus . 98 Dalbavancin is the first antibiotic approved by the FDA for the treatment of GPB (including MRSA) infection.…”

Dalbavancin for the Treatment of Prosthetic Joint Infections: A Narrative Review

“…Since almost all S. aureus strains that are vancomycin-susceptible are also DAL-susceptible, vancomycin susceptibility can be considered a surrogate marker of DAL activity. Consequently, vancomycin-resistant S. aureus (VRSA) is also resistant to DAL, and its usefulness against heteroresistant vancomycin-intermediate S. aureus (hVISA) is currently a matter for debate [26]. The loss of susceptibility against other anti-Gram-positive antibiotics (i.e., teicoplanin, telavancin, daptomycin, and linezolid) does not correlate with a decrease in DAL activity [27].…”