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. 1991 Nov;35(11):2388–2394. doi: 10.1128/aac.35.11.2388

Antibiotic-induced release of endotoxin in chronically bacteriuric patients.

J C Hurley 1, W J Louis 1, F A Tosolini 1, J B Carlin 1
PMCID: PMC245390  PMID: 1804012

Abstract

A novel in vivo model for the study of antibiotic-induced release of endotoxin from gram-negative bacteria is described. The model uses the chronically colonized urinary tracts of patients whose spinal cords have been injured. At baseline, the organisms were present in the range of 1 x 10(3) to 2 x 10(7) CFU/ml, and the concentration of endotoxin ranged from 2 x 10(-1) to 1 x 10(3) ng/ml in 44 studies. In 10 control studies, the concentration of endotoxin and the numbers of viable gram-negative bacteria over time changed by an average of less than 0.15 log10 units from the baseline values. At 2 h after antibiotic administration, the average decrease in CFU was 0.93 log10 units, and because antibiotics cause the release of endotoxin, an average increase in endotoxin concentration of 0.59 log10 units was noted in 21 studies with susceptible bacteria. Similar changes in response to antibiotic exposure were seen in studies with susceptible Pseudomonas bacteria in comparison with those seen in studies with susceptible members of the family Enterobacteriaceae. These results provide evidence that this novel model may be useful for comparing the effects of antibiotics with different modes of action, both as single agents and in combination, on the concentration of endotoxin in relation to changes in the numbers of bacteria, under conditions of bacterial replication and antibiotic exposure more closely resembling those found in vivo than is possible in other models.

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Selected References

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

  1. Andersen B. M., Solberg O. The endotoxin-liberating effect of antibiotics on meningococci in vitro. Acta Pathol Microbiol Scand B. 1980 Aug;88(4):231–236. doi: 10.1111/j.1699-0463.1980.tb02633.x. [DOI] [PubMed] [Google Scholar]
  2. COLLINS F. M. THE EFFECT OF THE GROWTH RATE ON THE COMPOSITION OF S. ENTERITIDIS CELL WALLS. Aust J Exp Biol Med Sci. 1964 Apr;42:255–262. doi: 10.1038/icb.1964.27. [DOI] [PubMed] [Google Scholar]
  3. Cattell W. R., Fry I. K., Spiro F. I., Sardeson J. M., Sutcliffe M. B., O'Grady F. Effect of diuresis and frequent micturition on the bacterial content of infected urine: a measure of competence of intrinsic hydrokinetic clearance mechanisms. Br J Urol. 1970 Jun;42(3):290–295. doi: 10.1111/j.1464-410x.1970.tb11922.x. [DOI] [PubMed] [Google Scholar]
  4. Cohen J., McConnell J. S. Release of endotoxin from bacteria exposed to ciprofloxacin and its prevention with polymyxin B. Eur J Clin Microbiol. 1986 Feb;5(1):13–17. doi: 10.1007/BF02013454. [DOI] [PubMed] [Google Scholar]
  5. Cosio F. G., Innes J. T., Nahman N. S., Jr, Mahan J. D., Ferguson R. M. Combined nephrotoxic effects of cyclosporine and endotoxin. Transplantation. 1987 Sep;44(3):425–428. doi: 10.1097/00007890-198709000-00020. [DOI] [PubMed] [Google Scholar]
  6. Cozens R. M., Tuomanen E., Tosch W., Zak O., Suter J., Tomasz A. Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat. Antimicrob Agents Chemother. 1986 May;29(5):797–802. doi: 10.1128/aac.29.5.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davis B. B. The lethal action of aminoglycosides. J Antimicrob Chemother. 1988 Jul;22(1):1–3. doi: 10.1093/jac/22.1.1. [DOI] [PubMed] [Google Scholar]
  8. Demonty J., De Graeve J. Release of endotoxic lipopolysaccharide by sensitive strains of Escherichia coli submitted to the bactericidal action of human serum. Med Microbiol Immunol. 1982;170(4):265–277. doi: 10.1007/BF02123317. [DOI] [PubMed] [Google Scholar]
  9. Fierer J., Finley F., Braude A. I. Release of 51Cr-endotoxin from bacteria as an assay of serum bactericidal activity. J Immunol. 1974 Jun;112(6):2184–2192. [PubMed] [Google Scholar]
  10. Flynn P. M., Shenep J. L., Gigliotti F., Davis D. S., Hildner W. K. Immunolabeling of lipopolysaccharide liberated from antibiotic-treated Escherichia coli. Infect Immun. 1988 Oct;56(10):2760–2762. doi: 10.1128/iai.56.10.2760-2762.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galanos C., Freudenberg M. A., Lüderitz O., Rietschel E. T., Westphal O. Chemical, physicochemical and biological properties of bacterial lipopolysaccharides. Prog Clin Biol Res. 1979;29:321–332. [PubMed] [Google Scholar]
  12. Gilbert P., Collier P. J., Brown M. R. Influence of growth rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy, and stringent response. Antimicrob Agents Chemother. 1990 Oct;34(10):1865–1868. doi: 10.1128/aac.34.10.1865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goto H., Nakamura S. Liberation of endotoxin from Escherichia coli by addition of antibiotics. Jpn J Exp Med. 1980 Feb;50(1):35–43. [PubMed] [Google Scholar]
  14. Greenwood D. In vitro veritas? Antimicrobial susceptibility tests and their clinical relevance. J Infect Dis. 1981 Oct;144(4):380–385. doi: 10.1093/infdis/144.4.380. [DOI] [PubMed] [Google Scholar]
  15. Levner M., Wiener F. P., Rubin B. A. Induction of Escherichia coli and Vibrio cholerae enterotoxins by an inhibitor of protein synthesis. Infect Immun. 1977 Jan;15(1):132–137. doi: 10.1128/iai.15.1.132-137.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mattsby-Baltzer I., Lindgren K., Lindholm B., Edebo L. Endotoxin shedding by enterobacteria: free and cell-bound endotoxin differ in Limulus activity. Infect Immun. 1991 Feb;59(2):689–695. doi: 10.1128/iai.59.2.689-695.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morse S. A., Mintz C. S., Sarafian S. K., Bartenstein L., Bertram M., Apicella M. A. Effect of dilution rate on lipopolysaccharide and serum resistance of Neisseria gonorrhoeae grown in continuous culture. Infect Immun. 1983 Jul;41(1):74–82. doi: 10.1128/iai.41.1.74-82.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ngeleka M., Beauchamp D., Tardif D., Auclair P., Gourde P., Bergeron M. G. Endotoxin increases the nephrotoxic potential of gentamicin and vancomycin plus gentamicin. J Infect Dis. 1990 Apr;161(4):721–727. doi: 10.1093/infdis/161.4.721. [DOI] [PubMed] [Google Scholar]
  19. Pearson A. D., Ellwood D. C. Growth environment and bacterial toxicity. J Med Microbiol. 1974 Aug;7(3):391–393. doi: 10.1099/00222615-7-3-391. [DOI] [PubMed] [Google Scholar]
  20. Ramsey R. B., Hamner M. B., Alving B. M., Finlayson J. S., Alving C. R., Evatt B. L. Effects of lipid A and liposomes containing lipid A on platelet and fibrinogen production in rabbits. Blood. 1980 Aug;56(2):307–310. [PubMed] [Google Scholar]
  21. Richardson E. C., Banerji B., Seid R. C., Jr, Levin J., Alving C. R. Interactions of lipid a and liposome-associated lipid A with Limulus polyphemus amoebocytes. Infect Immun. 1983 Mar;39(3):1385–1391. doi: 10.1128/iai.39.3.1385-1391.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Røkke O., Revhaug A., Osterud B., Giercksky K. E. Increased plasma levels of endotoxin and corresponding changes in circulatory performance in a porcine sepsis model: the effect of antibiotic administration. Prog Clin Biol Res. 1988;272:247–262. [PubMed] [Google Scholar]
  23. Shand G. H., Anwar H., Kadurugamuwa J., Brown M. R., Silverman S. H., Melling J. In vivo evidence that bacteria in urinary tract infection grow under iron-restricted conditions. Infect Immun. 1985 Apr;48(1):35–39. doi: 10.1128/iai.48.1.35-39.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shenep J. L., Barton R. P., Mogan K. A. Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis. J Infect Dis. 1985 Jun;151(6):1012–1018. doi: 10.1093/infdis/151.6.1012. [DOI] [PubMed] [Google Scholar]
  25. Shenep J. L., Flynn P. M., Barrett F. F., Stidham G. L., Westenkirchner D. F. Serial quantitation of endotoxemia and bacteremia during therapy for gram-negative bacterial sepsis. J Infect Dis. 1988 Mar;157(3):565–568. doi: 10.1093/infdis/157.3.565. [DOI] [PubMed] [Google Scholar]
  26. Smith H. Microbial surfaces in relation to pathogenicity. Bacteriol Rev. 1977 Jun;41(2):475–500. doi: 10.1128/br.41.2.475-500.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taylor P. W. Bactericidal and bacteriolytic activity of serum against gram-negative bacteria. Microbiol Rev. 1983 Mar;47(1):46–83. doi: 10.1128/mr.47.1.46-83.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tesh V. L., Morrison D. C. The interaction of Escherichia coli with normal human serum: factors affecting the capacity of serum to mediate lipopolysaccharide release. Microb Pathog. 1988 Mar;4(3):175–187. doi: 10.1016/0882-4010(88)90068-x. [DOI] [PubMed] [Google Scholar]
  29. Tune B. M., Hsu C. Y. Augmentation of antibiotic nephrotoxicity by endotoxemia in the rabbit. J Pharmacol Exp Ther. 1985 Aug;234(2):425–430. [PubMed] [Google Scholar]
  30. Täuber M. G., Shibl A. M., Hackbarth C. J., Larrick J. W., Sande M. A. Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits. J Infect Dis. 1987 Sep;156(3):456–462. doi: 10.1093/infdis/156.3.456. [DOI] [PubMed] [Google Scholar]
  31. Vanhaecke E., De Muynck C., Remon J. P., Colardyn F. Endotoxin removal by end-line filters. J Clin Microbiol. 1989 Dec;27(12):2710–2712. doi: 10.1128/jcm.27.12.2710-2712.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wright S. D., Levine R. P. How complement kills E. coli. II. The apparent two-hit nature of the lethal event. J Immunol. 1981 Sep;127(3):1152–1156. [PubMed] [Google Scholar]
  33. Yoh M., Yamamoto K., Honda T., Takeda Y., Miwatani T. Effects of lincomycin and tetracycline on production and properties of enterotoxins of enterotoxigenic Escherichia coli. Infect Immun. 1983 Nov;42(2):778–782. doi: 10.1128/iai.42.2.778-782.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zinner S. H., Husson M., Klastersky J. An artificial capillary in vitro kinetic model of antibiotic bactericidal activity. J Infect Dis. 1981 Dec;144(6):583–587. doi: 10.1093/infdis/144.6.583. [DOI] [PubMed] [Google Scholar]

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