The concomitant use of low concentration β-lactam antibiotics antagonizes the activity of vancomycin against some strains of MRSA. These strains, called β-lactam antibioticinduced vancomycin resistant MRSA (BIVR), have been increasing for a number of years. We previously reported that the combination of VCM and ceftizoxime displayed this antagonism not only in vitro, but also in vivo, in a systemic infection caused by BIVR in mice.
In the present study, we validated the antagonism in combinations of VCM with other β-lactams, i.e., flomoxef (FMOX), ampicillin (AMPC), azthreonam (AZT) and imipenem/cilastatin (IPM/CS), in systemic infections and pneumoniain in mice. The survival rate of the mice with systemic infections caused by BIVR treated with combinations of FMOX, AMPC, AZT, and IPM/CS with VCM were significantly lower than with VCM monotherapy, and the number of residual viable cells in the kidneys of mice treated with combinations of FMOX and IPM/CS with VCM were significantly higher than with VCM monotherapy The number of residual viable cells in the lungs of mice with pneumonia caused by BIVR treated with the combination of IPM/CS and VCM was significantly higher than with VCM monotherapy.
On the other hand, the survival rate with combination therapy consistings IPM/CS plus teicoplanin (TEIC) was significantly higher, and the number of residual viable cells in the kidney was significantly lower, than with TEIC monotherapy alone. In the mice with pneumonia, the number of residual viable cells in the lung after combination therapy with IPM/CS and TEIC was significantly lower than with TEIC monotherapy.
Combination therapy with P-lactams plus VCM showed antagonistic in models of systemic infection and pulmonary infection caused by BIVR, whereas combination therapy consisting of a β-lactam plus TEIC had a synergistic effect in the same models, even though VCM and TEIC are member of the same glycopeptide antibiotic class.