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Antimicrobial Agents and Chemotherapy, November 1999, p. 2720-2725, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effects of Genes Encoding Resistance to Streptogramins A and B on the Activity of Quinupristin-Dalfopristin against Enterococcus faecium

Bülent Bozdogan1 and Roland Leclercq1,2,*

Service de Microbiologie, Hôpital Côte de Nacre, Université de Caen, 14033 Caen,1 and Service de Bactériologie-Virologie, Hôpital Henri Mondor-Université Paris XII, 94000 Créteil,2 France

Received 14 May 1999/Returned for modification 20 July 1999/Accepted 31 August 1999

Quinupristin-dalfopristin is a streptogramin combination active against multiply resistant Enterococcus faecium. Among 45 E. faecium isolated from patients in various French hospitals, only two strains were intermediate (MIC = 2 µg/ml) and one, E. faecium HM1032, was resistant (MIC = 16 µg/ml) to quinupristin-dalfopristin, according to British Society for Antimicrobial Chemotherapy and National Committee for Clinical Laboratory Standards approved breakpoints. The latter strain contained the vgb and satA genes responsible for hydrolysis or acetylation of quinupristin and dalfopristin, respectively, and an ermB gene (also previously referred to as ermAM) encoding a ribosomal methylase. The two intermediate strains had an LSA phenotype characterized by resistance to lincomycin (L), increased MICs (>= 8 µg/ml) of dalfopristin (streptogramin A [SA]), and susceptibility to erythromycin and quinupristin. This phenotype was also detected in eight other strains susceptible to quinupristin-dalfopristin. No genes already known and conferring resistance to dalfopristin by acetylation or active efflux were detected in these LSA strains. Nineteen other strains resistant to erythromycin but susceptible to the quinupristin-dalfopristin combination displayed elevated MICs of quinupristin after induction (from 16 to >128 µg/ml) and contained ermB genes. The effects of ermB, vgb, and satA genes on the activity of the streptogramin combination were tested by cloning these genes individually or in various combinations in recipient strains susceptible to quinupristin-dalfopristin, E. faecium HM1070 and Staphylococcus aureus RN4220. The presence of both the satA and vgb genes (regardless of the presence of an ermB gene) was necessary to confer full quinupristin-dalfopristin resistance to the host. The same genetic constructs were introduced into E. faecium BM4107 which displays a LSA phenotype. Addition of the satA or vgb gene to this LSA background conferred resistance to quinupristin-dalfopristin.

* Corresponding author. Mailing address: CHU de Caen, Service de Microbiologie, Avenue Côte de Nacre, 14033 Caen Cedex, France. Phone: (33) 2 31 06 45 72. Fax: (33) 2 31 06 45 73. E-mail: leclercq-r{at}chu-caen.fr.

Antimicrobial Agents and Chemotherapy, November 1999, p. 2720-2725, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.