Evaluation of quinupristin/dalfopristin (Synercid (R)) and RPR 106 972 stability in susceptibility testing media

ln response to conflicting reports on the chemical stability of quinupristi n/dalfopristin. a study was designed to assess the in vitro longevity and e ffects of media and storage conditions on this streptogramin combination. B roth microdilution trays containing parenteral (quinupristin/dalfopristin) and oral (RPR 106972) streptogramin combinations as well as pristinomycin c omponents (P-I and P-II) were preincubated at 35 degrees C for 12-72 h befo re inoculation with control strains (Strepyococcus pneumoniae ATCC 49 619, Haemophilus influenzae ATCC 49247, Enterococcus faecalis ATCC 29212, Staphy lococcus aureus ATCC 29313) and five clinical isolates with various drug re sistance phenotypes. Overall, the mean quinupristin/dalfopristin activity l oss was 24%/12 h, 41%/18 h, 43%/24 h, 69%/48 h and 79%/72 h with no detecte d loss of potency when measured by E. faecalis until 18 h. RPR 106972 mean activity loss was 6%/12 h, 19%/18 h, 19%/24 h, 56%/48 h and 71%/72 h with n o loss of potency as measured by S. aureus until 48 h. Overall, P-I compone nts had greater stability as compared with P-II for both drug combinations. Bioassays showed similar trends in decreased activity. Bioassay difference s among media types were only significant (> 3 mm; greater loss of potency) for haemophilus test media for both P-II components at 72 h. The presence of an organism in the medium had no effect on stability assay results. The effect of storage temperature (4, 25 degrees C) on quinnpristin/dalfopristi n and RPR 106972 stability was also detrimental to drug potency indicating the requirement for rigid quality assurance for streptogramin diagnostic re agents when determining activity by reference or standardized susceptibilit y tests. (C) 2000 Elsevier Science B.V. and International Society of Chemot herapy. All rights reserved.