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Antimicrobial Agents and Chemotherapy, May 2002, p. 1319-1324, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1319-1324.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antimicrobial Activity of Quinupristin-Dalfopristin Combined with Other Antibiotics against Vancomycin-Resistant Enterococci

G. M. Eliopoulos^1,2* and C. B. Wennersten¹

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215,¹ Harvard Medical School, Boston, Massachusetts 02115²

Received 4 May 2001/ Returned for modification 19 November 2001/ Accepted 6 February 2002

Interactions between quinupristin-dalfopristin and six other antimicrobials were examined by checkerboard arrays against 50 clinical isolates of vancomycin-resistant Enterococcus faecium selected to represent a range of susceptibilities to individual agents. Unequivocal synergistic or antagonistic interactions at clinically relevant concentrations were infrequently encountered when the streptogramin was combined with chloramphenicol, ampicillin, imipenem, vancomycin, or teicoplanin. Combinations with doxycycline resulted in synergistic inhibition in 36% of checkerboards. Against 10 strains of Enterococcus faecalis, synergistic interactions were found when quinupristin-dalfopristin was combined with doxycycline (four strains), either glycopeptide (three strains), or ampicillin (two strains). Combination with quinupristin-dalfopristin increased the ampicillin MIC from 1 to 4 µg/ml for one strain. For 10 strains of E. faecium, interactions were also assessed by time-kill methods using concentrations of the agents attainable in human serum. Most of these antimicrobials augmented killing by quinupristin-dalfopristin to a minor degree. Against 2 of the 12 strains in this collection that were not highly resistant to gentamicin, the combination of quinupristin-dalfopristin (2 µg/ml) plus gentamicin (5 µg/ml) resulted in killing approaching 3 log₁₀ CFU/ml. With the exception of doxycycline, inhibitory interactions between quinupristin-dalfopristin and other agents tested against vancomycin-resistant strains of E. faecium were uncommon at clinically relevant concentrations.

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* Corresponding author. Mailing address: Department of Medicine, Beth Israel Deaconess Medical Center, One Deaconess Rd., Boston, MA 02215. Phone: (617) 632-8586. Fax: (617) 632-7442. E-mail: geliopou{at}caregroup.harvard.edu.

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Antimicrobial Agents and Chemotherapy, May 2002, p. 1319-1324, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1319-1324.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Bethea, J A., Walko, C. M, Targos, P. A (2004). Treatment of Vancomycin-Resistant Enterococcus with Quinupristin/Dalfopristin and High-Dose Ampicillin. The Annals of Pharmacotherapy 38: 989-991 [Abstract] [Full Text]  
• Brown, J., Freeman, B. B III (2004). Combining Quinupristin/Dalfopristin with Other Agents for Resistant Infections. The Annals of Pharmacotherapy 38: 677-685 [Abstract] [Full Text]