In vitro antimicrobial activity and MIC quality control guidelines of RPR 106972 (RPR 112808/RPR106950): A novel orally administered streptogramin combination

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RPR 106972 is a novel oral streptogramin combination with reported therapeutic potency against Gram-positive and certain respiratory tract pathogens. MICs for RPR 106972, quinupristin/dalfopristin, and seven comparison drugs were determined by the reference methods against 337 strains selected to define spectrum and potency. RPR 106972 demonstrated antimicrobial activity against oxacillin-susceptible and -resistant Staphylococcus aureus (MIC ranges of 0.12 to 2 μg/ml and 0.5 to 2 μg/ml, respectively), and coagulase-negative staphylococci were also inhibited by RPR 106972 (MIC 90′, ≤ 0.5 μg/ml) and quinupristin/dalfopristin (MIC 90′, ≤ 0.25 μg/ml). Against all streptococcal strains tested (including penicillin-resistant pneumococcus), RPR 106972 was highly active with MIC results at ≤ 1 μg/ml. RPR 106972 inhibited Corynebacterium jeikeium (MIC 90′ 0.5 μg/ml), Moraxella catarrhalis (MIC 90′, 0.25 μg/ml), and some Haemophilus influenzae (MIC 50′, 2 μg/ml). RPR 106972 and quinupristin/dalfopristin demonstrated little activity against Enterococcus faecalis (MIC 90s, 4 to 32 μg/ml) as compared to Enterococcus faecium (MIC 90s, 0.5 to 1 μg/ml) and other Enterococcus ssp. (MIC 90s, 1 μg/ml). Studies to establish MIC quality-control guidelines indicated the following ranges: for E. faecalis ATCC 29212, 0.5 to 4 μg/ml; for S. aureus ATCC 29213, 0.25 to 1 μg/ml; and for Streptococcus pneumoniae ATCC 49619, 0.06 to 0.5 μg/ml. The results of this study indicate that the in vitro activity of RPR 106972 against Gram-positive bacteria and selected Gram-negative respiratory organisms is promising and warrants additional studies of pharmacokinetics, and in vivo infection model dynamics.