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. 1997 Jun;41(6):1293–1297. doi: 10.1128/aac.41.6.1293

In vitro activities of ciprofloxacin and rifampin alone and in combination against growing and nongrowing strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

D Bahl 1, D A Miller 1, I Leviton 1, P Gialanella 1, M J Wolin 1, W Liu 1, R Perkins 1, M H Miller 1
PMCID: PMC163902  PMID: 9174186

Abstract

We characterized the effects of ciprofloxacin and rifampin alone and in combination on Staphylococcus aureus in vitro. The effects of drug combinations (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition were compared by disk approximation studies and by determining the fractional inhibitory concentrations. Bactericidal effects in log-phase bacteria and in nongrowing isolates were characterized by time-kill methods. The effect of drug combinations was dependent upon whether or not cells were growing and whether killing or growth inhibition was the endpoint used to measure drug interaction. Despite bactericidal antagonism in time-kill experiments, our in vitro studies suggest several possible explanations for the observed benefits in patients treated with a combination of ciprofloxacin and rifampin for deep-seated staphylococcal infections. Notably, when growth inhibition rather than killing was used to characterize drug interaction, indifference rather than antagonism was observed. An additive bactericidal effect was observed in nongrowing bacteria suspended in phosphate-buffered saline. While rifampin antagonized the bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the bactericidal effects of rifampin. Each antimicrobial prevented the emergence of subpopulations that were resistant to the other.

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Selected References

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  1. Akova M., Uzun O., Akalin H. E., Hayran M., Unal S., Gür D. Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin. Antimicrob Agents Chemother. 1993 Sep;37(9):1831–1834. doi: 10.1128/aac.37.9.1831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carbon C. Experimental endocarditis: a review of its relevance to human endocarditis. J Antimicrob Chemother. 1993 May;31 (Suppl 500):71–85. doi: 10.1093/jac/31.suppl_d.71. [DOI] [PubMed] [Google Scholar]
  3. Chambers H. F., Hartman B. J., Tomasz A. Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin. J Clin Invest. 1985 Jul;76(1):325–331. doi: 10.1172/JCI111965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chow R. T., Dougherty T. J., Fraimow H. S., Bellin E. Y., Miller M. H. Association between early inhibition of DNA synthesis and the MICs and MBCs of carboxyquinolone antimicrobial agents for wild-type and mutant [gyrA nfxB(ompF) acrA] Escherichia coli K-12. Antimicrob Agents Chemother. 1988 Aug;32(8):1113–1118. doi: 10.1128/aac.32.8.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Drlica K., Engle E. C., Manes S. H. DNA gyrase on the bacterial chromosome: possibility of two levels of action. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6879–6883. doi: 10.1073/pnas.77.11.6879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dworkin R. J., Lee B. L., Sande M. A., Chambers H. F. Treatment of right-sided Staphylococcus aureus endocarditis in intravenous drug users with ciprofloxacin and rifampicin. Lancet. 1989 Nov 4;2(8671):1071–1073. doi: 10.1016/s0140-6736(89)91083-0. [DOI] [PubMed] [Google Scholar]
  7. Dworkin R., Modin G., Kunz S., Rich R., Zak O., Sande M. Comparative efficacies of ciprofloxacin, pefloxacin, and vancomycin in combination with rifampin in a rat model of methicillin-resistant Staphylococcus aureus chronic osteomyelitis. Antimicrob Agents Chemother. 1990 Jun;34(6):1014–1016. doi: 10.1128/aac.34.6.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eng R. H., Padberg F. T., Smith S. M., Tan E. N., Cherubin C. E. Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria. Antimicrob Agents Chemother. 1991 Sep;35(9):1824–1828. doi: 10.1128/aac.35.9.1824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eng R. H., Smith S. M., Tillem M., Cherubin C. Rifampin resistance. Development during the therapy of methicillin-resistant Staphylococcus aureus infection. Arch Intern Med. 1985 Jan;145(1):146–148. doi: 10.1001/archinte.145.1.146. [DOI] [PubMed] [Google Scholar]
  10. Evans D. J., Allison D. G., Brown M. R., Gilbert P. Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate. J Antimicrob Chemother. 1991 Feb;27(2):177–184. doi: 10.1093/jac/27.2.177. [DOI] [PubMed] [Google Scholar]
  11. Fass R. J., Helsel V. L. In vitro antistaphylococcal activity of pefloxacin alone and in combination with other antistaphylococcal drugs. Antimicrob Agents Chemother. 1987 Oct;31(10):1457–1460. doi: 10.1128/aac.31.10.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hackbarth C. J., Chambers H. F., Sande M. A. Serum bactericidal activity of rifampin in combination with other antimicrobial agents against Staphylococcus aureus. Antimicrob Agents Chemother. 1986 Apr;29(4):611–613. doi: 10.1128/aac.29.4.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaatz G. W., Seo S. M., Barriere S. L., Albrecht L. M., Rybak M. J. Ciprofloxacin and rifampin, alone and in combination, for therapy of experimental Staphylococcus aureus endocarditis. Antimicrob Agents Chemother. 1989 Aug;33(8):1184–1187. doi: 10.1128/aac.33.8.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaatz G. W., Seo S. M., Ruble C. A. Mechanisms of fluoroquinolone resistance in Staphylococcus aureus. J Infect Dis. 1991 May;163(5):1080–1086. doi: 10.1093/infdis/163.5.1080. [DOI] [PubMed] [Google Scholar]
  15. Karchmer A. W. Staphylococcal endocarditis. Laboratory and clinical basis for antibiotic therapy. Am J Med. 1985 Jun 28;78(6B):116–127. doi: 10.1016/0002-9343(85)90374-2. [DOI] [PubMed] [Google Scholar]
  16. Lewin C. S., Amyes S. G. Conditions required for the bactericidal activity of fleroxacin and pefloxacin against Escherichia coli KL 16. J Med Microbiol. 1990 Jun;32(2):83–86. doi: 10.1099/00222615-32-2-83. [DOI] [PubMed] [Google Scholar]
  17. Miller M. H., Wexler M. A., Steigbigel N. H. Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants. Antimicrob Agents Chemother. 1978 Sep;14(3):336–343. doi: 10.1128/aac.14.3.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Neu H. C. Synergy and antagonism of combinations with quinolones. Eur J Clin Microbiol Infect Dis. 1991 Apr;10(4):255–261. doi: 10.1007/BF01966998. [DOI] [PubMed] [Google Scholar]
  19. Neu H. C. Synergy of fluoroquinolones with other antimicrobial agents. Rev Infect Dis. 1989 Jul-Aug;11 (Suppl 5):S1025–S1035. doi: 10.1093/clinids/11.supplement_5.s1025. [DOI] [PubMed] [Google Scholar]
  20. Pascual A., García I., Ramirez de Arellano E., Perea E. J. Activity of sparfloxacin on Staphylococcus epidermidis attached to plastic catheters. J Antimicrob Chemother. 1995 Aug;36(2):425–430. doi: 10.1093/jac/36.2.425. [DOI] [PubMed] [Google Scholar]
  21. Smith J. T. Wirkmechanismus der Chinolone. Infection. 1986;14 (Suppl 1):S3–15. doi: 10.1007/BF01645191. [DOI] [PubMed] [Google Scholar]
  22. Widmer A. F., Frei R., Rajacic Z., Zimmerli W. Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections. J Infect Dis. 1990 Jul;162(1):96–102. doi: 10.1093/infdis/162.1.96. [DOI] [PubMed] [Google Scholar]
  23. Widmer A. F., Gaechter A., Ochsner P. E., Zimmerli W. Antimicrobial treatment of orthopedic implant-related infections with rifampin combinations. Clin Infect Dis. 1992 Jun;14(6):1251–1253. doi: 10.1093/clinids/14.6.1251. [DOI] [PubMed] [Google Scholar]
  24. Zeiler H. J. Evaluation of the in vitro bactericidal action of ciprofloxacin on cells of Escherichia coli in the logarithmic and stationary phases of growth. Antimicrob Agents Chemother. 1985 Oct;28(4):524–527. doi: 10.1128/aac.28.4.524. [DOI] [PMC free article] [PubMed] [Google Scholar]

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