This Article
Right arrow Abstract Freely available
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 Goldstein, E. J. C.
Right arrow Articles by Bryskier, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldstein, E. J. C.
Right arrow Articles by Bryskier, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2005, p. 408-413, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.408-413.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative In Vitro Activities of XRP 2868, Pristinamycin, Quinupristin-Dalfopristin, Vancomycin, Daptomycin, Linezolid, Clarithromycin, Telithromycin, Clindamycin, and Ampicillin against Anaerobic Gram-Positive Species, Actinomycetes, and Lactobacilli

Ellie J. C. Goldstein,1,2* Diane M. Citron,1 C. Vreni Merriam,1 Yumi A. Warren,1 Kerin L. Tyrrell,1 Helen T. Fernandez,1 and Andre Bryskier3

R. M. Alden Research Laboratory, Santa Monica,1 UCLA School of Medicine, Los Angeles, California,2 Aventis Pharmaceuticals, Romainville, France3

Received 30 May 2004/ Returned for modification 31 August 2004/ Accepted 25 September 2004


arrow
ABSTRACT
 
A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were ≤0.5 µg/ml. XRP 2868 MICs for only two strains, one being Clostridium clostridioforme (MIC, 16 µg/ml) and the other being Clostridium difficile (MIC, 32 µg/ml), were >2 µg/ml. Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.


arrow
TEXT
 
Streptogramins are naturally occurring bacteriostatic antibiotics derived from Streptomyces pristinaspiralis and act on the 50S ribosome by inhibition of protein synthesis (6). Derivatives include pristinamycin, which has been available in Europe for >30 years, and quinupristin-dalfopristin, which is available as an injectable combination agent in the United States. While individual streptogramins are bacteriostatic, group A and B streptogramins given in combination act synergistically and may be bactericidal.

XRP 2868 is a new oral streptogramin that is comprised of a mixture of 70% RPR 132552A (group A, PII component) and 30% RPR 202868 (group B, PI component). Pankuch et al. (5) studied the activities of XRP 2868 against 261 pneumococci and 150 Haemophilus influenzae strains and found that XRP 2868 "showed potent activity" against all strains "irrespective of their susceptibility to other agents."

Barriere et al. (J. C. Barriere, E. Bacque, N. Berthaud, G. Dutruc-Rooset, G. Doerflinger, and G. Puchault, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-359, p. 207, 2001) noted that XPR 2868 has an antibacterial spectrum that "includes gram-positive cocci, fastidious gram-negative bacilli,...and anaerobes" and suggested that it was of potential value for the therapy of respiratory tract infections. Berthaud et al. (N. Berthaud, N. Diallo, B. Prevost, S. Lannier-Bonnamour, A. De Usatorre, and J. Hodgson, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-360, p. 207, 2001) noted that XRP 2868 has bactericidal activity against Staphylococcus aureus in a biofilm model.

In order to extend information about XRP 2868, we studied its comparative in vitro activities against 266 clinical isolates of anaerobic gram-positive organisms.

Strains were isolated from clinical specimens obtained from adult patients between 1996 and 2002 and identified by standard criteria (2, 3). Strains were consecutive isolates. S. aureus ATCC 29213 and Eubacterium lentum ATCC 43055 were tested simultaneously. The numbers and species of clinical isolates tested are given in Table 1.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Comparative in vitro activities of XRP 2868 against 264 recent clinical isolates of gram-positive anaerobic species, actinomycetes, and lactobacilli

Suppliers of laboratory susceptibility powders were Aventis Pharmaceuticals, Romainville, France, for XRP 2868, pristinamycin, telithromycin, and quinupristin-dalfopristin; Eli Lilly & Co., Indianapolis, Ind., for vancomyin; Cubist Pharmaceuticals, Lexington, Mass., for daptomycin; Pharmacia, Kalamazoo, Mich., for linezolid; and Sigma Chemicals, St. Louis, Mo., for ampicillin and clindamycin.

Susceptibility testing was performed according to methods in National Committee for Clinical Laboratory Standards standards (4), using an agar dilution method with brucella agar supplemented with hemin, vitamin K1, and 5% laked sheep blood and an inoculum of 105 CFU per spot. Daptomycin was supplemented with Ca2+ (50 mg/liter) as suggested by the manufacturer and in accordance with previously published findings (1). XRP 2868 was dissolved in dimethylformamide, according to the manufacturer's instructions, in a ratio of 30% RPR 202868 (PI component) and 70% RPR 132552A (PII component).

The results of our study are shown in Table 1. Overall, XRP 2868 had excellent activity against a broad range of gram-positive anaerobic bacteria, including actinomycetes, clostridia, eubacteria, Propionibacterium species, and peptostreptococci. Overall, XRP 2868 MICs for 95% (254 of 266) of isolates were ≤0.5 µg/ml. XRP 2868 MICs for only two strains, one being Clostridium difficile and the other being Clostridium clostridioforme, were >2 µg/ml. XRP 2868 was generally similar to or 1 dilution more active in vitro than pristinamycin and often 1 to 4 dilutions more active than quinupristin-dalfopristin. For the C. clostridioforme isolate for which the XRP MIC was 16 µg/ml, pristinamycin MICs were 16 µg/ml, quinupristin-dalfopristin MICs were 8 µg/ml, daptomycin MICs were 8 µg/ml, and ampicillin, clarithromycin, and telithromycin MICs were >32 µg/ml. The vancomycin MICs were 1 µg/ml, and the linezolid and clindamycin MICs were 2 µg/ml. In comparison, for the C. difficile isolate for which the XRP MIC was 32 µg/ml, pristinamycin MICs were 16 µg/ml; clarithromycin, telithromycin, and clindamycin MICs were >32 µg/ml; linezolid MICs were 8 µg/ml; ampicillin and quinupristin-dalfopristin MICs were 2 µg/ml; daptomycin MICs were 1 µg/ml; and vancomycin MICs were 0.5 µg/ml.

Daptomycin had decreased activity (MIC > 4 µg/ml) against 14 strains of Actinomyces spp. and all Clostridium ramosum, E. lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC, 4 µg/ml) against all strains of C. ramosum, 2 strains of C. difficile, and 15 strains of Lactobacillus spp. Ampicillin MICs were >1 µg/ml for eight strains of Clostridium spp. and three strains of Lactobacillus casei.

Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.


arrow
ACKNOWLEDGMENTS
 
We thank Alice E. Goldstein and Judee H. Knight for various forms of assistance.

We acknowledge support from Aventis Pharmaceuticals, Romainville, France.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: 2021 Santa Monica Blvd., Suite 740 East, Santa Monica, CA 90404. Phone: (310) 315-1511. Fax: (310) 315-3662. E-mail: ejcgmd{at}aol.com. Back


arrow
REFERENCES
 
    1
  1. Goldstein, E. J. C., D. M. Citron, C. V. Merriam, Y. A. Warren, K. L. Tyrrell, and H. T. Fernandez. 2003. In vitro activity of daptomycin, vancomycin, quinupristin-dalfopristin, linezolid, and five other antimicrobials against 307 gram-positive anaerobic and 31 Corynebacterium clinical isolates. Antimicrob. Agents Chemother. 47:337-341.[Abstract/Free Full Text]
    2. 2
  2. Jousimies-Somer, H. R., P. Summanen, D. M. Citron, E. J. Baron, H. M. Wexler, and S. M. Finegold. 2002. Wadsworth-KTL anaerobic bacteriology manual, 6th ed. Star Publishing Company, Belmont, Calif.
    3. 3
  3. Murray, P. R., E. J. Baron, J. H. Jorgensen, M. A. Pfaller, and R. H. Yolken. 2003. Manual of clinical microbiology, 8th ed. ASM Press, Washington, D.C.
    4. 4
  4. National Committee for Clinical Laboratory Standards. 2001. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 5th ed. Approved standard M11-A5. National Committee for Clinical Laboratory Standards, Wayne, Pa.
    5. 5
  5. Pankuch, G. A., L. M. Kelly, G. Lin, A. Bryskier, C. Couturier, M. R. Jacobs, and P. C. Appelbaum. 2003. Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and Haemophilus species. Antimicrob. Agents Chemother. 47:3270-3274.[Abstract/Free Full Text]
    6. 6
  6. Rybak, M. J., and J. R. Aeschlimann. 1998. Streptogramins, p. 963-972. In V. L. Yu, T. C. Merrigan, Jr., and S. L. Barriere (ed.), Antimicrobial therapy and vaccines. Williams & Wilkins, Baltimore, Md.

Antimicrobial Agents and Chemotherapy, January 2005, p. 408-413, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.408-413.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pankuch, G. A., Hoellman, D., Bryskier, A., Lowther, J., Appelbaum, P. C. (2006). Effects of Various Media on the Activity of NXL103 (Formerly XRP 2868), a New Oral Streptogramin, against Haemophilus influenzae. Antimicrob. Agents Chemother. 50: 3914-3916 [Abstract] [Full Text]  
  • Tyrrell, K. L., Citron, D. M., Warren, Y. A., Fernandez, H. T., Merriam, C. V., Goldstein, E. J. C. (2006). In Vitro Activities of Daptomycin, Vancomycin, and Penicillin against Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes.. Antimicrob. Agents Chemother. 50: 2728-2731 [Abstract] [Full Text]  
  • Dupuis, M., Leclercq, R. (2006). Activity of a New Oral Streptogramin, XRP2868, against Gram-Positive Cocci Harboring Various Mechanisms of Resistance to Streptogramins. Antimicrob. Agents Chemother. 50: 237-242 [Abstract] [Full Text]  
  • Andes, D., Craig, W. A. (2006). Pharmacodynamics of a New Streptogramin, XRP 2868, in Murine Thigh and Lung Infection Models. Antimicrob. Agents Chemother. 50: 243-249 [Abstract] [Full Text]  
  • Eliopoulos, G. M., Ferraro, M. J., Wennersten, C. B., Moellering, R. C. Jr. (2005). In Vitro Activity of an Oral Streptogramin Antimicrobial, XRP2868, against Gram-Positive Bacteria. Antimicrob. Agents Chemother. 49: 3034-3039 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
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 Goldstein, E. J. C.
Right arrow Articles by Bryskier, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldstein, E. J. C.
Right arrow Articles by Bryskier, A.

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