title: In vitro antimicrobial activity and MIC quality control guidelines of RPR 106972 (RPR 112808/RPR106950): a novel orally administered streptogramin combination. The Quality Control Study Group.
abstract: 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 micrograms/ml and 0.5 to 2 micrograms/ml, respectively), and coagulase-negative staphylococci were also inhibited by RPR 106972 (MIC90, < or = 0.5 microgram/ml) and quinupristin/dalfopristin (MIC90, < or = 0.25 microgram/ml). Against all streptococcal strains tested (including penicillin-resistant pneumococcus), RPR 106972 was highly active with MIC results at < or = 1 microgram/ml. RPR 106972 inhibited Corynebacterium jeikeium (MIC90, 0.5 microgram/ml). Moraxella catarrhalis (MIC90, 0.25 microgram/ml), and some Haemophilus influenzae (MIC50, 2 micrograms/ml). RPR 106972 and quinupristin/dalfopristin demonstrated little activity against Enterococcus faecalis (MIC90s, 4 to 32 micrograms/ml) as compared to Enterococcus faecium (MIC90s, 0.5 to 1 microgram/ml) and other Enterococcus ssp. (MIC90s, 1 microgram/ml). Studies to establish MIC quality-control guidelines indicated the following ranges: for E. faecalis ATCC 29212, 0.5 to 4 micrograms/ml; for S. aureus ATCC 29213, 0.25 to 1 microgram/ml; and for Streptococcus pneumoniae ATCC 49619, 0.06 to 0.5 microgram/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.
authors.affiliation: Department of Preventive Medicine and Environmental Health, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Putnam
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: D M
authors.initials: DM
authors.lastname: Johnson
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects / Q000302:isolation & purification; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006095:Gram-Positive Cocci / Q000187:drug effects* / Q000302:isolation & purification; D017408:Guidelines as Topic; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards; D011786:Quality Control; D013045:Species Specificity; D014769:Virginiamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; C099364:RPR 106972; D014769:Virginiamycin