Efficacy of Vancomycin-beta-lactam Combinations Against Heterogeneously Vancomycin-Resistant Staphylococcus aureus (hetero-VRSA)

Abstract

There have been conflicting data about the interactions between vancomycin and -lactam agents against Staphylococcus aureus strains with heterogeneous resistance to vancomycin. We evaluated the efficacy of these combinations against Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains which were isolated from Korean patients using a population analysis method. Antagonistic effects were observed when less than 1 g/mL of -lactam antibiotics was combined with vancomycin, whereas synergistic effects were noticed with more than 4 g/mL of -lactam antibiotics. The antagonistic effects at low concentrations of -lactams were most prominent at 2 g/mL of vancomycin, which were the vancomycin MICs of tested hetero-VRSA strains. This study showed the variable effects of vancomycin--lactam combinations depending on the concentrations of -lactam antibiotics and this property could be used to develop screening methods for hetero-VRSA strains.

Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA

“…However, previous studies 14 15 22 23 24 25 had conflicting findings regarding the combined effect of glycopeptides and various antibiotics against h-VISA/VISA isolates. In Kim et al .’s report 22 , an antagonistic effect was observed in combinations with less than 1 μg/ml β-lactam antibiotics – oxacillin and cefotaxime combined with vancomycin, whereas synergistic effects were noticed in combinations with more than 4 μg/ml β-lactams antibiotics. In Aritaka et al .’s study 23 , they noted that when combined with vancomycin, four of the seven tested β-lactams, including ampicillin, oxacillin, imipenem, and cefmetazole, exhibited an additive effect at or near their MICs; however, in contrast, all of the tested β-lactams showed an antagonistic effect at lower sub-MIC levels.…”

Relationship of Minimal Inhibitory Concentration and Bactericidal Activity to Efficacy of Antibiotics for Treatment of Ventilator-Associated Pneumonia

“…Combinations of amikacin þ sulbactam/ampicillin and b-lactams þ vancomycin have been tried or suggested for treatment of VISA or h-VRSA infections. [139][140][141][142] In addition, combinations of newer antibiotics with other antimicrobials are being investigated. [143][144][145] Among them, a couple of clinical reports have demonstrated synergy with vancomycin and Q-D in antimicrobial effect against MRSA.…”

Heteroresistance

“…It is based upon the observation that beta-lactam antibiotics (Aritaka et al, 2001; Y.S. Kim et al, 2003) and higher salinity can induce the phenotypic expression of vancomycin resistance and for this purpose aztreonam is preferred over other beta-lactam antibiotics because it has no inhibitory effect on Gram positive bacteria (Fig. 5).…”