Emergence of teicoplanin resistance during therapy of Staphylococcus aureus endocarditis

Serial isolates of Staphylococcus aureus showing two- to eightfold increases in teicoplanin minimum inhibitory concentrations (MICs) and twofold or less increases in MICs of other glycopeptides were recovered from the blood of a patient with endocarditis in whom drug therapy was unsuccessful. Comparable resistance emerged during teicoplanin treatment of rabbits with endocarditis caused by the original susceptible parent strain. For the parent strain, spontaneous resistance to teicoplanin at concentrations of 2-10 times the MIC was detected in vitro at frequencies of 10(-7) to 10(-9). Similar results were found for isolates of S. aureus from other geographic locations. Resistance was constitutive and not plasmid mediated, and its acquisition was not associated with changes in cytoplasmic membrane proteins. Teicoplanin was less effective than vancomycin at inhibiting peptidoglycan synthesis in resistant strains, suggesting that there is differential interference with the access of teicoplanin to or interaction with its target(s). Alternatively, teicoplanin and vancomycin may differ in some detail(s) of their mechanism of action against S. aureus.