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A Reference Broth Microdilution Method for Dalbavancin In Vitro Susceptibility Testing of Bacteria that Grow Aerobically
Published on: September 9, 2015
In Vitro Activity of Dalbavancin against Refractory Multidrug-Resistant (MDR) Staphylococcus aureus Isolates
Dafne Bongiorno1, Lorenzo Mattia Lazzaro1, Stefania Stefani1
1Department of Biomedical and Biotechnological Sciences (BIOMETEC)-Medical Molecular Microbiology and Antibiotic Resistance Laboratory (MMARLab), University of Catania, 95123 Catania, Italy.
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.
Insights
Dalbavancin shows strong antibacterial and bactericidal activity against resistant Staphylococcus aureus strains, including vancomycin-intermediate (VISA) and daptomycin non-susceptible (DNS) types. This makes dalbavancin a promising alternative for treating difficult MRSA infections.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections necessitates alternative treatments.
- Emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA), and daptomycin non-susceptible (DNS) S. aureus strains challenges current therapies.
- Glycopeptides and daptomycin are key treatments, but alternative options targeting resistant MRSA are crucial.
Purpose of the Study:
- To evaluate the in vitro antibacterial and bactericidal activity of dalbavancin.
- To assess dalbavancin's efficacy against a wide range of S. aureus resistance levels, including MDR, hVISA, DNS, and rifampicin-resistant (RIF-R) strains.
- To determine dalbavancin's potential as an alternative therapy for severe MRSA infections.
Main Methods:
- Tested susceptibility of 124 S. aureus strains to dalbavancin using broth microdilution.
- Included VISA, hVISA, vancomycin-resistant (VRSA), and methicillin-susceptible S. aureus (MSSA) reference strains.
- Assayed time-kill curves to evaluate bactericidal activity.
Main Results:
- Dalbavancin exhibited excellent in vitro antibacterial and bactericidal activity against all tested S. aureus resistance classes.
- Activity was confirmed against hVISA and DNS isolates.
- Rifampicin-resistant (RIF-R) strains showed the highest non-susceptibility, correlating with rpoB mutations and VISA/hVISA emergence.
Conclusions:
- Dalbavancin demonstrates significant in vitro efficacy against diverse S. aureus resistance phenotypes.
- The drug is a potential effective alternative for managing severe MRSA infections, including those with refractory resistance.
- Dalbavancin offers a viable option against challenging MRSA strains like hVISA and DNS.

