Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model

In the past 2 decades, multidrug-resistant Streptococcus pneumoniae has bee n encountered with increasing frequency around the world, This has led to t he need for newer agents in the treatment of S. pneumoniae infections, Orit avancin (LY333328) is a new glycopeptide antibiotic with activity against g ram-positive organisms; however, there is limited information on the pharma codynamics of oritavancin with respect to the treatment of S. pneumoniae, W e utilized an in vitro pharmacodynamic model to compare the activity of ori tavancin to that of vancomycin against two penicillin-, macrolide-, and cip rofloxacin-resistant S. pneumoniae isolates (R919 and R921) over a 48-h per iod. Both oritavancin and vancomycin achieved 99.9% (3-log) kill, with orit avancin achieving the limit of detection (10(2) CFU/ml) within 1 h and vanc omycin achieving this limit at 24 h for both isolates, Detection of resista nce was not observed for oritavancin or vancomycin during the 48-h experime nts, The key pharmacodynamic parameter for oritavancin has not been well de fined. In our experiment, the ratios of the area under the curve from 0 to 24 h to the MIC of oritavancin, oritavancin plus albumin, and vancomycin fo r both isolates were greater than 944.5, and the ratios of the maximum conc entration of drug in serum to the MIC ranged from 73.7 to 7188.5, T > MIC w as 100% for oritavancin and vancomycin for both isolates, Oritavancin is a unique and potent antimicrobial that warrants further investigation against multidrug-resistant S. pneumoniae.