Vancomycin and dalbavancin exposure led to MRSA cross-resistance to dalbavancin, vancomycin, and daptomycin, but cefadroxil showed synergy with dalbavancin against resistant strains.
Long-term suppression of MRSA LVAD infections with vancomycin and dalbavancin can lead to multi-drug cross-resistance, highlighting a potential role for synergistic combination therapy with agents like cefadroxil.
Absolute Event Rate: 0% vs 0%
Abstract We present a case in which vancomycin and dalbavancin exposure preceded emergence of non-susceptibility to dalbavancin, vancomycin, and daptomycin in a strain of MRSA in the setting of a left ventricular assist device (LVAD) infection. We characterized 6 related but genetically unique isolates collected over more than 1 year of recurrent therapy and found the most resistant isolate acquired multiple walK-related mutations, which has been previously implicated in dalbavancin resistance with vancomycin and daptomycin cross-resistance. Using time-kills at subinhibitory exposures we found that cefadroxil is synergistic with dalbavancin against the susceptible and resistant strains. This is the first report of dalbavancin non-susceptibly associated with an LVAD infection, but dalbavancin resistance has been documented previously in association with treatment of endovascular infections. Combination therapy with synergistic and orally bioavailable agents like cefadroxil may be a reasonable strategy to enhance activity and possibly diminish resistance emergence to dalbavancin.
Stohs et al. (Fri,) reported a other. Vancomycin and dalbavancin exposure led to MRSA cross-resistance to dalbavancin, vancomycin, and daptomycin, but cefadroxil showed synergy with dalbavancin against resistant strains.