This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allen, G. P.
Right arrow Articles by Rybak, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allen, G. P.
Right arrow Articles by Rybak, M. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2002, p. 2606-2612, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2606-2612.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Quinupristin-Dalfopristin and Cefepime, Alone and in Combination with Various Antimicrobials, against Multidrug-Resistant Staphylococci and Enterococci in an In Vitro Pharmacodynamic Model

George P. Allen,1,2,{dagger} Raymond Cha,1,2 and Michael J. Rybak1,2,3*

College of Pharmacy and Allied Health Professions,2 School of Medicine, Wayne State University,3 Anti-Infective Research Laboratory, Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center, Detroit, Michigan 482011

Received 4 September 2001/ Returned for modification 11 February 2002/ Accepted 10 April 2002

Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional synergistic drug combinations for these bacteria is magnified. We evaluated a number of antimicrobial combinations, with a focus on quinupristin-dalfopristin (Q-D), cefepime, and linezolid, using a previously described in vitro pharmacodynamic model. The combination of Q-D with either linezolid or vancomycin, as well as the combination of cefepime-vancomycin, resulted in enhanced killing (>=2-log10 increase in killing versus the most-active single agent) against methicillin-resistant Staphylococcus aureus (MRSA) 494. An improved effect (<2 log10 kill increase in kill) against MRSA 494 was noted for cefepime plus either Q-D or linezolid, as well as linezolid-vancomycin. Similar relationships were observed for a methicillin-susceptible S. aureus isolate (isolate 1199). Against methicillin-resistant S. epidermidis R444, enhanced killing was achieved with the combination of cefepime-linezolid, while improvement was noted for vancomycin with either cefepime or linezolid. The combination of cefepime and vancomycin also achieved enhanced killing against a glycopeptide-intermediate-susceptible S. aureus isolate (isolate 992). The combination of linezolid and doxycycline achieved an enhanced effect against vancomycin-resistant Enterococcus faecalis (VREFc) and E. faecium. Q-D plus ampicillin or linezolid resulted in similar enhancement of activity against the VREFc isolate. The results of this study suggest a number of novel antimicrobial combinations that may be useful against staphylococci and enterococci. Combination regimens including cefepime, Q-D, and/or linezolid warrant further investigation for the treatment of refractive infections due to multidrug-resistant gram-positive pathogens.

* Corresponding author. Mailing address: Anti-Infective Research Laboratory, Department of Pharmacy Services (1B), Detroit Receiving Hospital and University Health Center, 4201 St. Antoine Blvd., Detroit, MI 48201. Phone: (313) 577-4376. Fax: (313) 577-8915. E-mail: m.rybak{at}wayne.edu.

{dagger} Present address: Oregon State College of Pharmacy at OHSU, Portland, OR 97201-3098.

Antimicrobial Agents and Chemotherapy, August 2002, p. 2606-2612, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2606-2612.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nguyen, H. M., Graber, C. J. (2009). Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?. J Antimicrob Chemother 0: dkp377v1-dkp377 [Abstract] [Full Text]  
  • Zinner, S. H., Gilbert, D., Lubenko, I. Yu., Greer, K., Firsov, A. A. (2008). Selection of linezolid-resistant Enterococcus faecium in an in vitro dynamic model: protective effect of doxycycline. J Antimicrob Chemother 61: 629-635 [Abstract] [Full Text]  
  • Scheetz, M. H., Qi, C., Warren, J. R., Postelnick, M. J., Zembower, T., Obias, A., Noskin, G. A. (2007). In Vitro Activities of Various Antimicrobials Alone and in Combination with Tigecycline against Carbapenem-Intermediate or -Resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51: 1621-1626 [Abstract] [Full Text]  
  • Boak, L. M., Li, J., Rayner, C. R., Nation, R. L. (2007). Pharmacokinetic/Pharmacodynamic Factors Influencing Emergence of Resistance to Linezolid in an In Vitro Model. Antimicrob. Agents Chemother. 51: 1287-1292 [Abstract] [Full Text]  
  • Tsuji, B. T., Rybak, M. J., Lau, K. L., Sakoulas, G. (2007). Evaluation of Accessory Gene Regulator (agr) Group and Function in the Proclivity towards Vancomycin Intermediate Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 51: 1089-1091 [Abstract] [Full Text]  
  • Tsuji, B. T., Rybak, M. J. (2005). Short-Course Gentamicin in Combination with Daptomycin or Vancomycin against Staphylococcus aureus in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob. Agents Chemother. 49: 2735-2745 [Abstract] [Full Text]  
  • Huang, V., Rybak, M. J. (2005). Pharmacodynamics of Cefepime Alone and in Combination with Various Antimicrobials against Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Infection Model. Antimicrob. Agents Chemother. 49: 302-308 [Abstract] [Full Text]  
  • LaPlante, K. L., Rybak, M. J. (2004). Impact of High-Inoculum Staphylococcus aureus on the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model. Antimicrob. Agents Chemother. 48: 4665-4672 [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]  
  • Krueger, W. A., Kottler, B., Will, B. E., Heininger, A., Guggenberger, H., Unertl, K. E. (2004). Treatment of Meningitis Due to Methicillin-Resistant Staphylococcus epidermidis with Linezolid. J. Clin. Microbiol. 42: 929-932 [Abstract] [Full Text]  
  • Cha, R., Brown, W. J., Rybak, M. J. (2003). Bactericidal Activities of Daptomycin, Quinupristin-Dalfopristin, and Linezolid against Vancomycin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob. Agents Chemother. 47: 3960-3963 [Abstract] [Full Text]  
  • Kuklin, N. A., Pancari, G. D., Tobery, T. W., Cope, L., Jackson, J., Gill, C., Overbye, K., Francis, K. P., Yu, J., Montgomery, D., Anderson, A. S., McClements, W., Jansen, K. U. (2003). Real-Time Monitoring of Bacterial Infection In Vivo: Development of Bioluminescent Staphylococcal Foreign-Body and Deep-Thigh-Wound Mouse Infection Models. Antimicrob. Agents Chemother. 47: 2740-2748 [Abstract] [Full Text]  
  • Cha, R., Rybak, M. J. (2003). Linezolid and Vancomycin, Alone and in Combination with Rifampin, Compared with Moxifloxacin against a Multidrug-Resistant and a Vancomycin-Tolerant Streptococcus pneumoniae Strain in an In Vitro Pharmacodynamic Model. Antimicrob. Agents Chemother. 47: 1984-1987 [Abstract] [Full Text]  
  • Jacqueline, C., Caillon, J., Le Mabecque, V., Miegeville, A.-F., Donnio, P.-Y., Bugnon, D., Potel, G. (2003). In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time-kill curve methods. J Antimicrob Chemother 51: 857-864 [Abstract] [Full Text]  
  • Moyenuddin, M., Ohl, C. A., Williamson, J. C., Peacock, J. E. (2003). Disseminated oxacillin-resistant Staphylococcus aureus infection responsive to vancomycin and quinupristin-dalfopristin combination therapy. J Antimicrob Chemother 51: 202-203 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»