Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Apr;40(4):886–890. doi: 10.1128/aac.40.4.886

Intracellular activities of RP 59500 (quinupristin-dalfopristin) and sparfloxacin against Enterococcus faecium.

I Herrera-Insúa 1, K Jacques-Palaz 1, B E Murray 1, R M Rakita 1
PMCID: PMC163224  PMID: 8849245

Abstract

RP 59500, a combination of the streptogramins quinupristin and dalfopristin, and sparfloxacin are new antibiotics with good in vitro activities against Enterococcus faecium, which is an increasingly important nosocomial pathogen with resistance to multiple antimicrobials. Since fluoroquinolones and related macrolides have displayed high intracellular concentrations inside host cells, we evaluated the intracellular activities of these agents inside neutrophils against three strains each of vancomycin-susceptible E. faecium (VSEF) and vancomycin-resistant E. faecium (VREF). At concentrations equal to four times the MIC, RP 59500 and sparfloxacin decreased the number of intracellular VSEF organisms, while both antibiotics were at best bacteriostatic against intracellular VREF strains. At concentrations equal to one-fourth of the MIC, both antibiotics were bacteriostatic against intracellular VSEF strains but were ineffective in inhibiting the growth of VREF strains. Despite their anticipated markedly higher intracellular human neutrophil (PMN) concentrations, RP 59500 and sparfloxacin activities in medium alone were equal to or greater than those inside PMNs against almost all strains. We conclude that the intracellular PMN concentrations of these antibiotics may not be directly related to their intracellular activities in our assay. The reason for the differences in their activities against VSEF versus VREF remains undefined.

Full Text

The Full Text of this article is available as a PDF (201.3 KB).

Selected References

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

  1. Arduino R. C., Jacques-Palaz K., Murray B. E., Rakita R. M. Resistance of Enterococcus faecium to neutrophil-mediated phagocytosis. Infect Immun. 1994 Dec;62(12):5587–5594. doi: 10.1128/iai.62.12.5587-5594.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arthur M., Courvalin P. Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1563–1571. doi: 10.1128/aac.37.8.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bouanchaud D. H. In-vitro and in-vivo synergic activity and fractional inhibitory concentration (FIC) of the components of a semisynthetic streptogramin, RP 59500. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):95–99. doi: 10.1093/jac/30.suppl_a.95. [DOI] [PubMed] [Google Scholar]
  4. Brumfitt W., Hamilton-Miller J. M., Shah S. In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):29–37. doi: 10.1093/jac/30.suppl_a.29. [DOI] [PubMed] [Google Scholar]
  5. Clark N. C., Cooksey R. C., Hill B. C., Swenson J. M., Tenover F. C. Characterization of glycopeptide-resistant enterococci from U.S. hospitals. Antimicrob Agents Chemother. 1993 Nov;37(11):2311–2317. doi: 10.1128/aac.37.11.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collins L. A., Malanoski G. J., Eliopoulos G. M., Wennersten C. B., Ferraro M. J., Moellering R. C., Jr In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms. Antimicrob Agents Chemother. 1993 Mar;37(3):598–601. doi: 10.1128/aac.37.3.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Desnottes J. F., Diallo N. Cellular uptake and intracellular bactericidal activity of RP 59500 in murine macrophages. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):107–115. doi: 10.1093/jac/30.suppl_a.107. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Fass R. J. In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci. Antimicrob Agents Chemother. 1991 Mar;35(3):553–559. doi: 10.1128/aac.35.3.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. García I., Pascual A., Guzman M. C., Perea E. J. Uptake and intracellular activity of sparfloxacin in human polymorphonuclear leukocytes and tissue culture cells. Antimicrob Agents Chemother. 1992 May;36(5):1053–1056. doi: 10.1128/aac.36.5.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goto S., Miyazaki S., Kaneko Y. The in-vitro activity of RP 59500 against gram-positive cocci. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):25–28. doi: 10.1093/jac/30.suppl_a.25. [DOI] [PubMed] [Google Scholar]
  12. Hand W. L., King-Thompson N. L. Contrasts between phagocyte antibiotic uptake and subsequent intracellular bactericidal activity. Antimicrob Agents Chemother. 1986 Jan;29(1):135–140. doi: 10.1128/aac.29.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Handwerger S., Raucher B., Altarac D., Monka J., Marchione S., Singh K. V., Murray B. E., Wolff J., Walters B. Nosocomial outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin. Clin Infect Dis. 1993 Jun;16(6):750–755. doi: 10.1093/clind/16.6.750. [DOI] [PubMed] [Google Scholar]
  14. Ishiguro M., Koga H., Kohno S., Hayashi T., Yamaguchi K., Hirota M. Penetration of macrolides into human polymorphonuclear leucocytes. J Antimicrob Chemother. 1989 Nov;24(5):719–729. doi: 10.1093/jac/24.5.719. [DOI] [PubMed] [Google Scholar]
  15. Megran D. W. Enterococcal endocarditis. Clin Infect Dis. 1992 Jul;15(1):63–71. doi: 10.1093/clinids/15.1.63. [DOI] [PubMed] [Google Scholar]
  16. Miranda A. G., Singh K. V., Murray B. E. DNA fingerprinting of Enterococcus faecium by pulsed-field gel electrophoresis may be a useful epidemiologic tool. J Clin Microbiol. 1991 Dec;29(12):2752–2757. doi: 10.1128/jcm.29.12.2752-2757.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mtairag E. M., Abdelghaffar H., Douhet C., Labro M. T. Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides. Antimicrob Agents Chemother. 1995 Aug;39(8):1676–1682. doi: 10.1128/aac.39.8.1676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Perri M. B., Chow J. W., Zervos M. J. In vitro activity of sparfloxacin and clinafloxacin against multidrug-resistant enterococci. Diagn Microbiol Infect Dis. 1993 Aug-Sep;17(2):151–155. doi: 10.1016/0732-8893(93)90026-4. [DOI] [PubMed] [Google Scholar]
  19. Rakita R. M., Jacques-Palaz K., Murray B. E. Intracellular activity of azithromycin against bacterial enteric pathogens. Antimicrob Agents Chemother. 1994 Sep;38(9):1915–1921. doi: 10.1128/aac.38.9.1915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Retsema J. A., Brennan L. A., Girard A. E. Effects of environmental factors on the in vitro potency of azithromycin. Eur J Clin Microbiol Infect Dis. 1991 Oct;10(10):834–842. doi: 10.1007/BF01975836. [DOI] [PubMed] [Google Scholar]
  21. Richard P., Gutmann L. Sparfloxacin and other new fluoroquinolones. J Antimicrob Chemother. 1992 Dec;30(6):739–744. doi: 10.1093/jac/30.6.739. [DOI] [PubMed] [Google Scholar]
  22. Rosen H., Michel B. R., Chait A. Phagocytosis of opsonized oil droplets by neutrophils. Adaptation to a microtiter plate format. J Immunol Methods. 1991 Nov 5;144(1):117–125. doi: 10.1016/0022-1759(91)90237-a. [DOI] [PubMed] [Google Scholar]
  23. Spera R. V., Jr, Farber B. F. Multiply-resistant Enterococcus faecium. The nosocomial pathogen of the 1990s. JAMA. 1992 Nov 11;268(18):2563–2564. [PubMed] [Google Scholar]
  24. Steinberg T. H. Cellular transport of drugs. Clin Infect Dis. 1994 Nov;19(5):916–921. doi: 10.1093/clinids/19.5.916. [DOI] [PubMed] [Google Scholar]
  25. Tenover F. C., Arbeit R. D., Goering R. V., Mickelsen P. A., Murray B. E., Persing D. H., Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995 Sep;33(9):2233–2239. doi: 10.1128/jcm.33.9.2233-2239.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tulkens P. M. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):100–106. doi: 10.1007/BF01964420. [DOI] [PubMed] [Google Scholar]
  27. Van der Auwera P., Matsumoto T., Husson M. Intraphagocytic penetration of antibiotics. J Antimicrob Chemother. 1988 Aug;22(2):185–192. doi: 10.1093/jac/22.2.185. [DOI] [PubMed] [Google Scholar]
  28. van den Broek P. J. Antimicrobial drugs, microorganisms, and phagocytes. Rev Infect Dis. 1989 Mar-Apr;11(2):213–245. doi: 10.1093/clinids/11.2.213. [DOI] [PubMed] [Google Scholar]

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

RESOURCES