MIC distribution and inoculum effect of LY333328: A study of vancomycin-susceptible and VanA-type and VanC-type enterococci obtained from intensive care unit patient surveillance cultures

Abstract

Objective: To determine the in vitro activity and inoculum effect of LY333328, a semisynthetic glycopeptide, against vancomycin-susceptible and vancomycin-resistant enterococcal isolates. Methods: One hundred and seventy-six enterococcal isolates (117 vancomycin-susceptible, 29 VanA-type and 30 VanC-type isolates) obtained from surveillance cultures of 139 intensive care unit patients were studied by the standard agar dilution method. Vancomycin resistance determinants were characterized by PCR. Results: The activity of LY333328 was comparable (MIC range, 0.1-2 mg/L) to those of vancomycin (0.1-4 mg/L) and teicoplanin (0.06-1 mg/L) for vancomycin-susceptible isolates. LY333328 was more active (0.1-8 mg/L) than vancomycin (256 to > 1024 mg/L) and teicoplanin (32-512 mg/L) against VanA-type isolates, and similar (0.2-1 mg/L) to teicoplanin (0.1-0.5 mg/L) against VanC-type isolates. The MIC distribution of LY333328 displayed a narrower range than that of vancomycin, with no clear distinction between susceptible and resistant populations. The increment in the inoculum size, from 104 to 106 CFU/spot, of susceptible isolates increased the MIC values of LY333328, vancomycin and teicoplanin by factors of 11.4, 1.6 and 3.8, respectively. The corresponding factors for LY333328 for VanA-type and VanC-type isolates were 3.5 and 6.4, respectively. Conclusions: LY333328 displays an excellent in vitro activity against vancomycin-susceptible and -resistant enterococci. Nevertheless, the inoculum size used in susceptibility tests should be carefully controlled.