Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 May;39(5):1038–1044. doi: 10.1128/aac.39.5.1038

Combination effect of fosfomycin and ofloxacin against Pseudomonas aeruginosa growing in a biofilm.

H Kumon 1, N Ono 1, M Iida 1, J C Nickel 1
PMCID: PMC162679  PMID: 7625785

Abstract

We examined the combined effect of fosfomycin and ofloxacin against Pseudomonas aeruginosa in biofilms by using an in vitro experimental system with a modified Robbins device. Sessile cells in a mature or immature biofilm, developed on a silicon disk, were used, and an ATP bioluminescence assay was employed to assess antibacterial effects. A synergistic effect of fosfomycin and ofloxacin was clearly detected when concentrations at which each drug independently produced no detectable decrease in the bioactivity of sessile cells were used. Exposure of the cells in a mature biofilm to fosfomycin at concentrations of one-eighth of the MIC to 10 times the MIC (6.25 to 500 micrograms/ml) and ofloxacin at three or 10 times the MIC (18.75 or 62.5 micrograms/ml) resulted in reduction of the bioactivity to 1.5 to 4.5% after 72 h. Young sessile cells in an immature biofilm were more susceptible to this combination therapy. With a combination of fosfomycin at three times the MIC and ofloxacin at three times the MIC, complete eradication was confirmed by both ATP assay and scanning electron microscopy.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

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

  1. Anwar H., Costerton J. W. Enhanced activity of combination of tobramycin and piperacillin for eradication of sessile biofilm cells of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1990 Sep;34(9):1666–1671. doi: 10.1128/aac.34.9.1666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anwar H., van Biesen T., Dasgupta M., Lam K., Costerton J. W. Interaction of biofilm bacteria with antibiotics in a novel in vitro chemostat system. Antimicrob Agents Chemother. 1989 Oct;33(10):1824–1826. doi: 10.1128/aac.33.10.1824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bergan T. Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives. Chemotherapy. 1990;36 (Suppl 1):10–18. doi: 10.1159/000238809. [DOI] [PubMed] [Google Scholar]
  4. Borowski J., Linda H. Combined action of fosfomycin with beta-lactam and aminoglycoside antibiotics. Chemotherapy. 1977;23 (Suppl 1):82–85. doi: 10.1159/000222030. [DOI] [PubMed] [Google Scholar]
  5. Costerton J. W., Lam J., Lam K., Chan R. The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S867–S873. doi: 10.1093/clinids/5.supplement_5.s867. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Figueredo V. M., Neu H. C. Synergy of ciprofloxacin with fosfomycin in vitro against Pseudomonas isolates from patients with cystic fibrosis. J Antimicrob Chemother. 1988 Jul;22(1):41–50. doi: 10.1093/jac/22.1.41. [DOI] [PubMed] [Google Scholar]
  8. Gordon C. A., Hodges N. A., Marriott C. Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa. J Antimicrob Chemother. 1988 Nov;22(5):667–674. doi: 10.1093/jac/22.5.667. [DOI] [PubMed] [Google Scholar]
  9. Gristina A. G. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science. 1987 Sep 25;237(4822):1588–1595. doi: 10.1126/science.3629258. [DOI] [PubMed] [Google Scholar]
  10. Hendlin D., Stapley E. O., Jackson M., Wallick H., Miller A. K., Wolf F. J., Miller T. W., Chaiet L., Kahan F. M., Foltz E. L. Phosphonomycin, a new antibiotic produced by strains of streptomyces. Science. 1969 Oct 3;166(3901):122–123. doi: 10.1126/science.166.3901.122. [DOI] [PubMed] [Google Scholar]
  11. Hoyle B. D., Costerton J. W. Bacterial resistance to antibiotics: the role of biofilms. Prog Drug Res. 1991;37:91–105. doi: 10.1007/978-3-0348-7139-6_2. [DOI] [PubMed] [Google Scholar]
  12. Kahan F. M., Kahan J. S., Cassidy P. J., Kropp H. The mechanism of action of fosfomycin (phosphonomycin). Ann N Y Acad Sci. 1974 May 10;235(0):364–386. doi: 10.1111/j.1749-6632.1974.tb43277.x. [DOI] [PubMed] [Google Scholar]
  13. Koch C., Høiby N. Pathogenesis of cystic fibrosis. Lancet. 1993 Apr 24;341(8852):1065–1069. doi: 10.1016/0140-6736(93)92422-p. [DOI] [PubMed] [Google Scholar]
  14. Kumon H., Kaneshige T., Ohmori H. T4-labeling technique and its applications with particular reference to blood group antigens in bladder tumors. Scan Electron Microsc. 1983;(Pt 2):939–948. [PubMed] [Google Scholar]
  15. Kumon H., Tomochika K., Matunaga T., Ogawa M., Ohmori H. A sandwich cup method for the penetration assay of antimicrobial agents through Pseudomonas exopolysaccharides. Microbiol Immunol. 1994;38(8):615–619. doi: 10.1111/j.1348-0421.1994.tb01831.x. [DOI] [PubMed] [Google Scholar]
  16. Lode H., Höffken G., Olschewski P., Sievers B., Kirch A., Borner K., Koeppe P. Pharmacokinetics of ofloxacin after parenteral and oral administration. Antimicrob Agents Chemother. 1987 Sep;31(9):1338–1342. doi: 10.1128/aac.31.9.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Minuth J. N., Musher D. M., Thorsteinsson S. B. Inhibition of the antibacterial activity of gentamicin by urine. J Infect Dis. 1976 Jan;133(1):14–21. doi: 10.1093/infdis/133.1.14. [DOI] [PubMed] [Google Scholar]
  18. Nichols W. W., Dorrington S. M., Slack M. P., Walmsley H. L. Inhibition of tobramycin diffusion by binding to alginate. Antimicrob Agents Chemother. 1988 Apr;32(4):518–523. doi: 10.1128/aac.32.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nickel J. C., Costerton J. W. Coagulase-negative staphylococcus in chronic prostatitis. J Urol. 1992 Feb;147(2):398–401. doi: 10.1016/s0022-5347(17)37247-6. [DOI] [PubMed] [Google Scholar]
  20. Nickel J. C., Olson M. E., Barabas A., Benediktsson H., Dasgupta M. K., Costerton J. W. Pathogenesis of chronic bacterial prostatitis in an animal model. Br J Urol. 1990 Jul;66(1):47–54. doi: 10.1111/j.1464-410x.1990.tb14864.x. [DOI] [PubMed] [Google Scholar]
  21. Nickel J. C., Ruseska I., Wright J. B., Costerton J. W. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Antimicrob Agents Chemother. 1985 Apr;27(4):619–624. doi: 10.1128/aac.27.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Takenaka T. [An ATP bioluminescence assay for the analysis of bacterial biofilms]. Kansenshogaku Zasshi. 1994 Jun;68(6):759–766. doi: 10.11150/kansenshogakuzasshi1970.68.759. [DOI] [PubMed] [Google Scholar]

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

RESOURCES