Evaluation of quinupristin/dalfopristin (Synercid) and RPR 106972 stability in susceptibility testing media

In response to conflicting reports on the chemical stability of quinupristin/dalfopristin, a study was designed to assess the in vitro longevity and effects of media and storage conditions on this streptogramin combination. Broth microdilution trays containing parenteral (quinupristin/dalfopristin) and oral (RPR 106972) streptogramin combinations as well as pristinomycin components (P-I and P-II) were preincubated at 35 degrees C for 12-72 h before inoculation with control strains (Streptococcus pneumoniae ATCC 49619, Haemophilus influenzae ATCC 49247, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213) and five clinical isolates with various drug resistance phenotypes. Overall, the mean quinupristin/dalfopristin activity loss was 24%/12 h, 41%/18 h, 43%/24 h, 69%/48 h and 79%/72 h with no detected 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 no loss of potency as measured by S. aureus until 48 h. Overall, P-I components had greater stability as compared with P-II for both drug combinations. Bioassays showed similar trends in decreased activity. Bioassay differences 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 quinupristin/dalfopristin and RPR 106972 stability was also detrimental to drug potency indicating the requirement for rigid quality assurance for streptogramin diagnostic reagents when determining activity by reference or standardized susceptibility tests.