Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 g/ml, respectively) and to low levels of teicoplanin (4 g/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 g/ml) and susceptible to teicoplanin (0.25 g/ml), were studied. Prior to the late 1980s, Enterococcus faecium and Enterococcus faecalis were considered uniformly susceptible to vancomycin, which was often the only antibiotic effective against multiresistant strains. Therefore, reports of vancomycin resistance in enterococci from Europe in 1988 (32, 48) and subsequently from the United States raised considerable concern (19). Since then, vancomycin-resistant enterococci have become increasingly prevalent.Glycopeptide resistance in enterococci results from the production of modified peptidoglycan precursors ending in D-Ala-D-Lac (VanA, VanB, and VanD) or D-Ala-D-Ser (VanC, VanE, and VanG), to which glycopeptides exhibit low binding affinities, and from the elimination of the high-affinity D-Ala-D-Ala-ending precursors synthesized by the host Ddl ligase (10,20,22,44). Acquired resistance to glycopeptides in the three D-Ala-D-Lac types, VanA, VanB, and VanD, can be classified depending on the levels of resistance to vancomycin and susceptibility or resistance to teicoplanin (10,22). VanA-type strains display high-level inducible resistance to both vancomycin and teicoplanin, whereas VanB-type strains have various levels of inducible resistance to vancomycin only, since teicoplanin is not an inducer (10). VanD-type strains are characterized by constitutive resistance to moderate levels of both glycopeptides (22)

The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e. duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae. Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA). Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period. SBA was determined, using the microdilution method. SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h). For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h). One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h. Two strains with two mutations (parC and gyrA) did not display any SBA. For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher). In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.