Activity of a New Oral Streptogramin, XRP2868, against Gram-Positive Cocci Harboring Various Mechanisms of Resistance to Streptogramins

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Abstract
The antibacterial activity of XRP2868, a new oral streptogramin composed of a combination of RPR132552 (streptogramin A) and RPR202868 (streptogramin B), was evaluated against a collection of clinical gram-positive isolates with characterized phenotypes and genotypes of streptogramin resistance. The effects of genes for resistance to streptogramin A or B on the activity of XRP2868 and its components were also tested by cloning these genes individually or in various combinations in gram-positive recipient strains susceptible to quinupristin-dalfopristin. The species tested included Staphylococcus aureus , coagulase-negative staphylococci, Enterococcus faecalis , Enterococcus faecium , Streptococcus pneumoniae , and other species of streptococci. XRP2868 was generally fourfold more potent than quinupristin-dalfopristin against S. aureus , E. faecium , and streptococci and had activity against E. faecalis (MICs = 0.25 to 1 μg/ml). XRP2868 appeared to be affected by the same mechanisms of resistance as those to quinupristin-dalfopristin. Nevertheless, the strong activity of factor A of the oral streptogramin enabled the combination to be very potent against streptogramin-susceptible staphylococci, streptococci, and E. faecium (MICs = 0.03 to 0.25 μg/ml) and to retain low MICs against the strains harboring a mechanism of resistance to factor A or factor B of the streptogramin. However, the combination of mechanisms of resistance to factors A and B caused an increase in the MICs of XRP2868, which reached 1 to 4 μg/ml. As with the other streptogramins, there was a reduction in the bactericidal effect of XRPR2868 when the staphylococcal strains acquired a constitutively expressed erm gene.

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