Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1988 Dec;32(12):1869–1874. doi: 10.1128/aac.32.12.1869

Norfloxacin binds to human fecal material.

C Edlund 1, L Lindqvist 1, C E Nord 1
PMCID: PMC176035  PMID: 2854456

Abstract

Earlier studies have reported very high (120 to 2,700 mg/kg) concentrations of norfloxacin in feces after therapeutic doses. MICs for fecal microorganisms are with few exceptions far below these levels. Nevertheless, clinical investigations show that the main part of the aerobic gram-positive and the anaerobic microflora remains unaffected after norfloxacin administration. In this study, the binding of [14C]norfloxacin to fecal material was analyzed. The binding of a group of nonlabeled quinolones to feces and the interactions between Enterococcus faecium, Bacteroides fragilis, and norfloxacin were also investigated. The results showed that norfloxacin has the ability to bind to feces. The specific binding was reversible, saturated after 90 min of incubation at 37 degrees C, and increased linearly with fecal concentration. Scatchard plots and nonlinear regression computer analyses revealed two different binding classes. The primary specific binding had a dissociation constant (KD) of 1.0 microM and a maximal binding capacity (Bmax) of 0.12 mumol/g of feces. The KD and Bmax of the secondary, more unspecific binding were 450 microM and 11.8 mumol/g of feces, respectively. The binding of unlabeled ciprofloxacin, enoxacin, ofloxacin, pefloxacin, and norfloxacin to feces was comparable to that of [14C]norfloxacin. The results of norfloxacin binding to suspensions of B. fragilis suggested that the main part of the binding is to the bacterial fraction of feces. In the presence of 8.0 g (dry weight) of B. fragilis per liter, the MBC of norfloxacin for E. faecium increased from 8 to 256 micrograms/ml. The finding of the present study indicated that binding of norfloxacin to feces may explain the paradox of high fecal concentrations of norfloxacin versus the actual effect on the normal gastrointestinal microflora.

Full text

PDF
1869

Selected References

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

  1. Bedard J., Wong S., Bryan L. E. Accumulation of enoxacin by Escherichia coli and Bacillus subtilis. Antimicrob Agents Chemother. 1987 Sep;31(9):1348–1354. doi: 10.1128/aac.31.9.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boerema J. B., Olthof B. J., van Saene H. K. Effects of norfloxacin on the faecal flora in patients with complicated urinary tract infections. Scand J Infect Dis Suppl. 1986;48:27–31. [PubMed] [Google Scholar]
  3. Borobio M. V., Perea E. J. Effect of inoculum, pH, and medium on the activity of ciprofloxacin against anaerobic bacteria. Antimicrob Agents Chemother. 1984 Mar;25(3):342–343. doi: 10.1128/aac.25.3.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chapman J. S., Georgopapadakou N. H. Routes of quinolone permeation in Escherichia coli. Antimicrob Agents Chemother. 1988 Apr;32(4):438–442. doi: 10.1128/aac.32.4.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cofsky R. D., duBouchet L., Landesman S. H. Recovery of norfloxacin in feces after administration of a single oral dose to human volunteers. Antimicrob Agents Chemother. 1984 Jul;26(1):110–111. doi: 10.1128/aac.26.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen S. P., Hooper D. C., Wolfson J. S., Souza K. S., McMurry L. M., Levy S. B. Endogenous active efflux of norfloxacin in susceptible Escherichia coli. Antimicrob Agents Chemother. 1988 Aug;32(8):1187–1191. doi: 10.1128/aac.32.8.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crumplin G. C., Kenwright M., Hirst T. Investigations into the mechanism of action of the antibacterial agent norfloxacin. J Antimicrob Chemother. 1984 May;13 (Suppl B):9–23. doi: 10.1093/jac/13.suppl_b.9. [DOI] [PubMed] [Google Scholar]
  8. Edlund C., Bergan T., Josefsson K., Solberg R., Nord C. E. Effect of norfloxacin on human oropharyngeal and colonic microflora and multiple-dose pharmacokinetics. Scand J Infect Dis. 1987;19(1):113–121. doi: 10.3109/00365548709032386. [DOI] [PubMed] [Google Scholar]
  9. Edlund C., Nord C. E. A review on the impact of 4-quinolones on the normal oropharyngeal and intestinal human microflora. Infection. 1988;16(1):8–12. doi: 10.1007/BF01646921. [DOI] [PubMed] [Google Scholar]
  10. Edlund C., Nord C. E. Comparative in vitro activities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against Bacteroides fragilis and Clostridium difficile. Scand J Infect Dis. 1986;18(2):149–151. doi: 10.3109/00365548609032321. [DOI] [PubMed] [Google Scholar]
  11. Goldstein E. J., Citron D. M., Corrado M. L. Effect of inoculum size on in vitro activity of norfloxacin against fecal anaerobic bacteria. Rationale for selective decontamination of the digestive tract. Am J Med. 1987 Jun 26;82(6B):84–87. doi: 10.1016/0002-9343(87)90625-5. [DOI] [PubMed] [Google Scholar]
  12. Hazenberg M. P., Pennock-Schröder A. M., van de Merwe J. P. Binding to and antibacterial effect of aztreonam, temocillin, gentamicin and tobramycin on human faeces. J Hyg (Lond) 1985 Oct;95(2):255–263. doi: 10.1017/s0022172400062689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hazenberg M. P., Pennock-Schröder A. M., van de Merwe J. P. Reversible binding of polymyxin B and neomycin to the solid part of faeces. J Antimicrob Chemother. 1986 Mar;17(3):333–339. doi: 10.1093/jac/17.3.333. [DOI] [PubMed] [Google Scholar]
  14. Hirai K., Aoyama H., Irikura T., Iyobe S., Mitsuhashi S. Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob Agents Chemother. 1986 Mar;29(3):535–538. doi: 10.1128/aac.29.3.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hooper D. C., Wolfson J. S. Mode of action of the quinolone antimicrobial agents. Rev Infect Dis. 1988 Jan-Feb;10 (Suppl 1):S14–S21. doi: 10.1093/clinids/10.supplement_1.s14. [DOI] [PubMed] [Google Scholar]
  16. Karp J. E., Merz W. G., Hendricksen C., Laughon B., Redden T., Bamberger B. J., Bartlett J. G., Saral R., Burke P. J. Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1987 Jan;106(1):1–7. doi: 10.7326/0003-4819-106-1-1. [DOI] [PubMed] [Google Scholar]
  17. Norrby S. R., Jonsson M. Antibacterial activity of norfloxacin. Antimicrob Agents Chemother. 1983 Jan;23(1):15–18. doi: 10.1128/aac.23.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reeves D. S. The effect of quinolone antibacterials on the gastrointestinal flora compared with that of other antibacterials. J Antimicrob Chemother. 1986 Nov;18 (Suppl 500):89–102. doi: 10.1093/jac/18.supplement_d.89. [DOI] [PubMed] [Google Scholar]
  19. Shen L. L., Pernet A. G. Mechanism of inhibition of DNA gyrase by analogues of nalidixic acid: the target of the drugs is DNA. Proc Natl Acad Sci U S A. 1985 Jan;82(2):307–311. doi: 10.1073/pnas.82.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stephen A. M., Cummings J. H. The microbial contribution to human faecal mass. J Med Microbiol. 1980 Feb;13(1):45–56. doi: 10.1099/00222615-13-1-45. [DOI] [PubMed] [Google Scholar]
  21. Zweerink M. M., Edison A. Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986 Apr;29(4):598–601. doi: 10.1128/aac.29.4.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. van Saene J. J., van Saene H. K., Stoutenbeek C. P., Lerk C. F. Influence of faeces on the activity of antimicrobial agents used for decontamination of the alimentary canal. Scand J Infect Dis. 1985;17(3):295–300. [PubMed] [Google Scholar]

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

RESOURCES