Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 May;29(5):760–764. doi: 10.1128/aac.29.5.760

Influence of inflammation on the efficacy of antibiotic treatment of experimental pyelonephritis.

P R Meylan, G Braoudakis, M P Glauser
PMCID: PMC284150  PMID: 3524429

Abstract

An acute exudative Escherichia coli pyelonephritis rat model was used to study the influence of progressive pyelonephritis on the efficacy of antibiotic treatment. In this model, transient ureteral obstruction after E. coli bladder inoculation induces early bacterial multiplication in the kidney parenchyma, and the bacterial counts peak by 48 h. The inflammatory response (assessed by the increase in kidney weight) is somewhat delayed, starting 36 h after inoculation and peaking by 72 h. Groups of rats received 4 doses over 48 h of saline, ceftriaxone (100 mg/kg), or ceftriaxone (100 mg/kg) plus gentamicin (4 mg/kg). These treatments were initiated 24, 36, 48, or 72 h after bladder inoculation. Antibiotic treatment started at 24 h was significantly more effective in reducing bacterial counts in the kidney parenchyma than at any later therapy onset. Only when started 24 h after inoculation was the synergistic combination of ceftriaxone plus gentamicin more effective in reducing bacterial counts than ceftriaxone alone. Ceftriaxone and ceftriaxone plus gentamicin regimens started at 24 h reduced significantly (by 42 and 55%, respectively) the incidence of acute exudative pyelonephritis when compared with the incidence in saline-treated controls. Early therapy onset (24 h) strikingly reduced the development of the inflammatory response. This reduction was less marked when antibiotic therapy was started at 36 h and no longer apparent when therapy onset was delayed up to 48 or 72 h. In conclusion, the efficacy of antibiotics in eradicating bacteria from the kidney parenchyma and in preventing acute exudative pyelonephritis was markedly hampered by the development of pyelonephritis.

Full text

PDF
760

Selected References

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

  1. Barza M., Weinstein L. Penetration of antibiotics into fibrin loci in vivo. I. Comparison of penetration of ampicillin into fibrin clots, abscesses, and "interstitial fluid". J Infect Dis. 1974 Jan;129(1):59–65. doi: 10.1093/infdis/129.1.59. [DOI] [PubMed] [Google Scholar]
  2. Bergeron M. G., Trottier S., Lessard C., Beauchamp D., Gagnon P. M. Disturbed intrarenal distribution of gentamicin in experimental pyelonephritis due to Escherichia coli. J Infect Dis. 1982 Sep;146(3):436–439. doi: 10.1093/infdis/146.3.436. [DOI] [PubMed] [Google Scholar]
  3. Bille J., Glauser M. P. Protection against chronic pyelonephritis in rats by suppression of acute suppuration: effect of colchicine and neutropenia. J Infect Dis. 1982 Aug;146(2):220–226. doi: 10.1093/infdis/146.2.220. [DOI] [PubMed] [Google Scholar]
  4. Brooks S. J., Lyons J. M., Braude A. I. Immunization against retrograde pyelonephritis. I. Production of an experimental model of severe ascending Escherichia coli pyelonephritis without bacteremia in rats. Am J Pathol. 1974 Feb;74(2):345–358. [PMC free article] [PubMed] [Google Scholar]
  5. Brooks S. J., Lyons J. M., Braude A. I. Immunization against retrograde pyelonephritis. II. Prevention of retrograde Escherichia coli pyelonephritis with vaccines. Am J Pathol. 1974 Feb;74(2):359–364. [PMC free article] [PubMed] [Google Scholar]
  6. Brooks S. J., Lyons J. M., Braude A. I. Immunization against retrograde pyelonephritis. III. Vaccination against chronic pyelonephritis due to Escherichia coli. J Infect Dis. 1977 Nov;136(5):633–639. doi: 10.1093/infdis/136.5.633. [DOI] [PubMed] [Google Scholar]
  7. Bryant R. E., Hammond D. Interaction of purulent material with antibiotics used to treat Pseudomonas infections. Antimicrob Agents Chemother. 1974 Dec;6(6):702–707. doi: 10.1128/aac.6.6.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Glauser M. P., Bonard Treatment of experimental ascending Escherichia coli pyelonephritis with ceftriaxone alone and in combination with gentamicin. Chemotherapy. 1982;28(5):410–416. doi: 10.1159/000238130. [DOI] [PubMed] [Google Scholar]
  9. Glauser M. P., Francioli P. B., Bille J., Bonard M., Meylan P. Effect of indomethacin on the incidence of experimental Escherichia coli pyelonephritis. Infect Immun. 1983 May;40(2):529–533. doi: 10.1128/iai.40.2.529-533.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Glauser M. P., Lyons J. M., Braude A. I. Prevention of chronic experimental pyelonephritis by suppression of acute suppuration. J Clin Invest. 1978 Feb;61(2):403–407. doi: 10.1172/JCI108951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glauser M. P., Lyons J. M., Braude A. I. Prevention of pyelonephritis due to Escherichia coli in rats with gentamicin stored in kidney tissue. J Infect Dis. 1979 Feb;139(2):172–177. doi: 10.1093/infdis/139.2.172. [DOI] [PubMed] [Google Scholar]
  12. Glauser M. P., Lyons J. M., Braude A. I. Synergism of ampicillin and gentamicin against obstructive pyelonephritis due to Escherichia coli in rats. J Infect Dis. 1979 Feb;139(2):133–140. doi: 10.1093/infdis/139.2.133. [DOI] [PubMed] [Google Scholar]
  13. Goodell E. W., Lopez R., Tomasz A. Suppression of lytic effect of beta lactams on Escherichia coli and other bacteria. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3293–3297. doi: 10.1073/pnas.73.9.3293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gorbach S. L., Bartlett J. G. Anaerobic infections (third of three parts). N Engl J Med. 1974 Jun 6;290(23):1289–1294. doi: 10.1056/NEJM197406062902305. [DOI] [PubMed] [Google Scholar]
  15. MacArthur R. D., Jackson G. G. An evaluation of the use of statistical methodology in the Journal of Infectious Diseases. J Infect Dis. 1984 Mar;149(3):349–354. doi: 10.1093/infdis/149.3.349. [DOI] [PubMed] [Google Scholar]
  16. Miller T., Phillips S. Pyelonephritis: the relationship between infection, renal scarring, and antimicrobial therapy. Kidney Int. 1981 May;19(5):654–662. doi: 10.1038/ki.1981.65. [DOI] [PubMed] [Google Scholar]
  17. Murray T., Goldberg M. Chronic interstitial nephritis: etiologic factors. Ann Intern Med. 1975 Apr;82(4):453–459. doi: 10.7326/0003-4819-82-4-453. [DOI] [PubMed] [Google Scholar]
  18. O'Keefe J. P., Tally F. P., Barza M., Gorbach S. L. Inactivation of penicillin G during experimental infection with Bacteroides fragilis. J Infect Dis. 1978 Apr;137(4):437–442. doi: 10.1093/infdis/137.4.437. [DOI] [PubMed] [Google Scholar]
  19. O'Keefe J. P., Tally F. P., Barza M., Gorbach S. L. Penetration of cephalothin and cefoxitin into experimental infections with Bacteroides fragilis. Rev Infect Dis. 1979 Jan-Feb;1(1):106–112. doi: 10.1093/clinids/1.1.106. [DOI] [PubMed] [Google Scholar]
  20. Ransley P. G., Risdon R. A. Reflux nephropathy: effects of antimicrobial therapy on the evolution of the early pyelonephritic scar. Kidney Int. 1981 Dec;20(6):733–742. doi: 10.1038/ki.1981.204. [DOI] [PubMed] [Google Scholar]
  21. Roberts J. A., Roth J. K., Jr, Domingue G., Lewis R. W., Kaack B., Baskin G. Immunology of pyelonephritis in the primate model. VI. Effect of complement depletion. J Urol. 1983 Jan;129(1):193–196. doi: 10.1016/s0022-5347(17)51981-3. [DOI] [PubMed] [Google Scholar]
  22. Sabath L. D., Gerstein D. A., Leaf C. D., Finland M. Increasing the usefulness of antibiotics: Treatment of infections caused by gram-negative bacilli. Clin Pharmacol Ther. 1970 Mar-Apr;11(2):161–167. doi: 10.1002/cpt1970112161. [DOI] [PubMed] [Google Scholar]
  23. Slotki I. N., Asscher A. W. Prevention of scarring in experimental pyelonephritis in the rat by early antibiotic therapy. Nephron. 1982;30(3):262–268. doi: 10.1159/000182484. [DOI] [PubMed] [Google Scholar]
  24. Vaudaux P., Waldvogel F. A. Gentamicin inactivation in purulent exudates: role of cell lysis. J Infect Dis. 1980 Oct;142(4):586–593. doi: 10.1093/infdis/142.4.586. [DOI] [PubMed] [Google Scholar]
  25. Verklin R. M., Jr, Mandell G. L. Alteration of effectiveness of antibiotics by anaerobiosis. J Lab Clin Med. 1977 Jan;89(1):65–71. [PubMed] [Google Scholar]

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

RESOURCES