Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 May;41(5):931–935. doi: 10.1128/aac.41.5.931

Influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B-type antibiotics in Enterococcus faecium on activity of quinupristin-dalfopristin in vitro and in rabbits with experimental endocarditis.

B Fantin 1, R Leclercq 1, L Garry 1, C Carbon 1
PMCID: PMC163828  PMID: 9145847

Abstract

The influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B (MLS(B)) type antibiotics (inducible MLS(B) phenotype) on the activity of quinupristin-dalfopristin was investigated against Enterococcus faecium in vitro and in rabbits with experimental endocarditis. In vitro, quinupristin-dalfopristin displayed bacteriostatic and bactericidal activities against a MLS(B)-susceptible strain similar to those against two strains with the inducible MLS(B) phenotype. In addition, induction of the two MLS(B)-resistant strains with quinupristin (0.016 to 1 microg/ml) or quinupristin-dalfopristin (0.08 to 0.25 microg/ml) increased the MICs of quinupristin from 8 microg/ml to 32 to > 128 microg/ml, but did not modify the MIC of dalfopristin (2 microg/ml) or quinupristin-dalfopristin (0.5 microg/ml). In a rabbit endocarditis model, quinupristin-dalfopristin was as active as amoxicillin against the MLS(B)-susceptible E. faecium strain. In contrast, the activity of quinupristin-dalfopristin was significantly decreased in animals infected with either of the two inducible MLS(B)-resistant strains (P < 0.05), although no mutants resistant to quinupristin-dalfopristin were detected. Against the clinical strain with the inducible MLS(B) phenotype, quinupristin-dalfopristin was not effective and was less active than amoxicillin (P < 0.001); however, the activity of the combination of amoxicillin and dalfopristin-quinupristin was superior to that of amoxicillin (P < 0.01). The different impact of the inducible MLS(B) phenotype in E. faecium on the activity of quinupristin-dalfopristin in vitro and in experimental endocarditis may be related to the reduced diffusion of dalfopristin compared with that of quinupristin into cardiac vegetations that we previously reported. This result emphasizes the importance of the constant presence of dalfopristin at the site of infection to ensure synergism with quinupristin.

Full Text

The Full Text of this article is available as a PDF (236.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Awada A., van der Auwera P., Meunier F., Daneau D., Klastersky J. Streptococcal and enterococcal bacteremia in patients with cancer. Clin Infect Dis. 1992 Jul;15(1):33–48. doi: 10.1093/clinids/15.1.33. [DOI] [PubMed] [Google Scholar]
  2. Chabbert Y. A., Courvalin P. Synergie des composants des antibiotiques du groupe de la streptogramine. Pathol Biol (Paris) 1971 Jun-Jul;19(11):613–619. [PubMed] [Google Scholar]
  3. Entenza J. M., Drugeon H., Glauser M. P., Moreillon P. Treatment of experimental endocarditis due to erythromycin-susceptible or -resistant methicillin-resistant Staphylococcus aureus with RP 59500. Antimicrob Agents Chemother. 1995 Jul;39(7):1419–1424. doi: 10.1128/aac.39.7.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Etienne S. D., Montay G., Le Liboux A., Frydman A., Garaud J. J. A phase I, double-blind, placebo-controlled study of the tolerance and pharmacokinetic behaviour of RP 59500. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):123–131. doi: 10.1093/jac/30.suppl_a.123. [DOI] [PubMed] [Google Scholar]
  5. Fantin B., Leclercq R., Merlé Y., Saint-Julien L., Veyrat C., Duval J., Carbon C. Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus. Antimicrob Agents Chemother. 1995 Feb;39(2):400–405. doi: 10.1128/aac.39.2.400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fantin B., Leclercq R., Ottaviani M., Vallois J. M., Maziere B., Duval J., Pocidalo J. J., Carbon C. In vivo activities and penetration of the two components of the streptogramin RP 59500 in cardiac vegetations of experimental endocarditis. Antimicrob Agents Chemother. 1994 Mar;38(3):432–437. doi: 10.1128/aac.38.3.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Horinouchi S., Byeon W. H., Weisblum B. A complex attenuator regulates inducible resistance to macrolides, lincosamides, and streptogramin type B antibiotics in Streptococcus sanguis. J Bacteriol. 1983 Jun;154(3):1252–1262. doi: 10.1128/jb.154.3.1252-1262.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kang S. L., Rybak M. J. Pharmacodynamics of RP 59500 alone and in combination with vancomycin against Staphylococcus aureus in an in vitro-infected fibrin clot model. Antimicrob Agents Chemother. 1995 Jul;39(7):1505–1511. doi: 10.1128/aac.39.7.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Leclercq R., Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother. 1991 Jul;35(7):1267–1272. doi: 10.1128/aac.35.7.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leclercq R., Nantas L., Soussy C. J., Duval J. Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):67–75. doi: 10.1093/jac/30.suppl_a.67. [DOI] [PubMed] [Google Scholar]
  11. Pankuch G. A., Jacobs M. R., Appelbaum P. C. MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci. Antimicrob Agents Chemother. 1996 Sep;40(9):2071–2074. doi: 10.1128/aac.40.9.2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Soussy C. J., Acar J. F., Cluzel R., Courvalin P., Duval J., Fleurette J., Megraud F., Meyran M., Thabaut A. A collaborative study of the in-vitro sensitivity to RP 59500 of bacteria isolated in seven hospitals in France. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):53–58. doi: 10.1093/jac/30.suppl_a.53. [DOI] [PubMed] [Google Scholar]
  14. Weisblum B. Inducible resistance to macrolides, lincosamides and streptogramin type B antibiotics: the resistance phenotype, its biological diversity, and structural elements that regulate expression--a review. J Antimicrob Chemother. 1985 Jul;16 (Suppl A):63–90. doi: 10.1093/jac/16.suppl_a.63. [DOI] [PubMed] [Google Scholar]
  15. el Solh N., Allignet J., Bismuth R., Buret B., Fouace J. M. Conjugative transfer of staphylococcal antibiotic resistance markers in the absence of detectable plasmid DNA. Antimicrob Agents Chemother. 1986 Jul;30(1):161–169. doi: 10.1128/aac.30.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES