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Antimicrobial Agents and Chemotherapy, January 2006, p. 237-242, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.237-242.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Michel Dupuis and Roland Leclercq*

Service de Microbiologie and EA 2128 Relations Hôte et Microorganismes des Épithéliums, Hôpital Côte de Nacre, Université de Caen, 14033 Caen cedex, France

Received 1 September 2005/ Returned for modification 21 September 2005/ Accepted 16 October 2005

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.

* Corresponding author: Mailing address: CHU de Caen, Service de Microbiologie, Avenue Côte de Nacre, 14033 Caen Cedex, France. Phone: (33) 02 31 06 45 72. Fax: (33) 02 31 06 45 73. E-mail: leclercq-r{at}chu-caen.fr.

Antimicrobial Agents and Chemotherapy, January 2006, p. 237-242, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.237-242.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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