Objective:
MRSA is now endemic in hospitals around the world with an estimated 1.5 million cases per year and causes significant morbidity and mortality. In this study, the in vitro activity of daptomycin, in combination with a genetically recombinant antibody targeting an ABC transporter, was examined in different isolates of epidemic methicillin resistant S. aureus (EMRSA).

Methods:
17 different isolates recovered from different outbreaks in England and Wales were selected as representatives of EMRSA isolates 1 to 17. Broth microdilution MICs and checkerboard titrations were carried out for daptomycin and the recombinant antibody alone and in combination. In addition, time-kill analysis was performed for EMRSA-16 using daptomycin in combination with various concentrations of the recombinant antibody according to the NCCLS standards M7-A7.

Results:
Checkerboard titrations showed synergistic or additive effects of the tested recombinant antibody when combined with daptomycin against all the tested EMRSA isolates. At 0.125µg/ml of daptomycin (0.5x MIC), the time-kill analysis of EMRSA-16 demonstrated that all the different concentrations (8-128ug/ml) of the tested recombinant antibody reduced the log₁₀ CFU/ml. At an antibody concentrations of 128 and 64 µg/ml, synergy were observed after 24h with 4.6 and 2.4 log₁₀ decrease in CFU/ml respectively. There were no examples of antagonism.

Conclusion:
The in vitro sensitivity of EMRSA strains to daptomycin was found to be increased when exposed to daptomycin in combination with the tested recombinant antibody. These data suggest that the combination of this recombinant antibody with daptomycin would be worth exploring in the treatment of infections due to MRSA.