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. 1994 Feb;38(2):200–204. doi: 10.1128/aac.38.2.200

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species.

P H Edelstein 1, M A Edelstein 1
PMCID: PMC284426  PMID: 8192443

Abstract

The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml). Erythromycin (1 microgram/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.

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Selected References

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  1. Dournon E., Mayaud C., Wolff M., Schlemmer B., Samuel D., Sollet J. P., Levasseur-Rajagopalan P. Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease. J Antimicrob Chemother. 1990 Oct;26 (Suppl B):129–139. doi: 10.1093/jac/26.suppl_b.129. [DOI] [PubMed] [Google Scholar]
  2. Dournon E., Rajagopalan P., Vilde J. L., Pocidalo J. J. Efficacy of pefloxacin in comparison with erythromycin in the treatment of experimental guinea pig legionellosis. J Antimicrob Chemother. 1986 Apr;17 (Suppl B):41–48. doi: 10.1093/jac/17.suppl_b.41. [DOI] [PubMed] [Google Scholar]
  3. Edelstein P. H., Beer K. B., DeBoynton E. D. Influence of growth temperature on virulence of Legionella pneumophila. Infect Immun. 1987 Nov;55(11):2701–2705. doi: 10.1128/iai.55.11.2701-2705.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Edelstein P. H., Calarco K., Yasui V. K. Antimicrobial therapy of experimentally induced Legionnaires' disease in guinea pigs. Am Rev Respir Dis. 1984 Nov;130(5):849–856. doi: 10.1164/arrd.1984.130.5.849. [DOI] [PubMed] [Google Scholar]
  5. Edelstein P. H., Edelstein M. A., Holzknecht B. In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother. 1992 Nov;36(11):2387–2391. doi: 10.1128/aac.36.11.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edelstein P. H., Edelstein M. A. In vitro activity of Ro 23-9424 against clinical isolates of Legionella species. Antimicrob Agents Chemother. 1992 Nov;36(11):2559–2561. doi: 10.1128/aac.36.11.2559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Edelstein P. H., Edelstein M. A. WIN 57273 is bactericidal for Legionella pneumophila grown in alveolar macrophages. Antimicrob Agents Chemother. 1989 Dec;33(12):2132–2136. doi: 10.1128/aac.33.12.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edelstein P. H., Edelstein M. A., Weidenfeld J., Dorr M. B. In vitro activity of sparfloxacin (CI-978; AT-4140) for clinical Legionella isolates, pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother. 1990 Nov;34(11):2122–2127. doi: 10.1128/aac.34.11.2122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edelstein P. H., Meyer R. D. Legionnaires' disease. A review. Chest. 1984 Jan;85(1):114–120. doi: 10.1378/chest.85.1.114. [DOI] [PubMed] [Google Scholar]
  10. Fitzgeorge R. B., Featherstone A. S., Baskerville A. Efficacy of azithromycin in the treatment of guinea pigs infected with Legionella pneumophila by aerosol. J Antimicrob Chemother. 1990 Jan;25 (Suppl A):101–108. doi: 10.1093/jac/25.suppl_a.101. [DOI] [PubMed] [Google Scholar]
  11. Fitzgeorge R. B., Gibson D. H., Jepras R. I., Baskerville A. Efficacy of imipenem in experimental Legionnaires' disease. Lancet. 1985 Mar 16;1(8429):633–634. doi: 10.1016/s0140-6736(85)92164-6. [DOI] [PubMed] [Google Scholar]
  12. Havlichek D., Saravolatz L., Pohlod D. Effect of quinolones and other antimicrobial agents on cell-associated Legionella pneumophila. Antimicrob Agents Chemother. 1987 Oct;31(10):1529–1534. doi: 10.1128/aac.31.10.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hohl P., Buser U., Frei R. Fatal Legionella pneumophila pneumonia: treatment failure despite early sequential oral-parenteral amoxicillin-clavulanic acid therapy. Infection. 1992 Mar-Apr;20(2):99–100. doi: 10.1007/BF01711076. [DOI] [PubMed] [Google Scholar]
  14. Jones R. N., Thornsberry C., Wilson H. W., McDougal L. K. The in vitro activity of sulphones alone and in combination with ampicillin or amoxicillin against Legionella pneumophila and other Legionella spp. including beta-lactamase studies. Diagn Microbiol Infect Dis. 1985 Mar;3(2):179–183. doi: 10.1016/0732-8893(85)90029-x. [DOI] [PubMed] [Google Scholar]
  15. Kirby B. D., Snyder K. M., Meyer R. D., Finegold S. M. Legionnaires' disease: report of sixty-five nosocomially acquired cases of review of the literature. Medicine (Baltimore) 1980 May;59(3):188–205. [PubMed] [Google Scholar]
  16. Kitsukawa K., Hara J., Saito A. Inhibition of Legionella pneumophila in guinea pig peritoneal macrophages by new quinolone, macrolide and other antimicrobial agents. J Antimicrob Chemother. 1991 Mar;27(3):343–353. doi: 10.1093/jac/27.3.343. [DOI] [PubMed] [Google Scholar]
  17. Kurz R. W., Graninger W., Egger T. P., Pichler H., Tragl K. H. Failure of treatment of legionella pneumonia with ciprofloxacin. J Antimicrob Chemother. 1988 Sep;22(3):389–391. doi: 10.1093/jac/22.3.389. [DOI] [PubMed] [Google Scholar]
  18. Mandell G. L. Interaction of intraleukocytic bacteria and antibiotics. J Clin Invest. 1973 Jul;52(7):1673–1679. doi: 10.1172/JCI107348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Myburgh J., Nagel G. J., Petschel E. The efficacy and tolerance of a three-day course of azithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother. 1993 Jun;31 (Suppl E):163–169. doi: 10.1093/jac/31.suppl_e.163. [DOI] [PubMed] [Google Scholar]
  20. Nowicki M., Paucod J. C., Bornstein N., Meugnier H., Isoard P., Fleurette J. Comparative efficacy of five antibiotics on experimental airborne legionellosis in guinea-pigs. J Antimicrob Chemother. 1988 Oct;22(4):513–519. doi: 10.1093/jac/22.4.513. [DOI] [PubMed] [Google Scholar]
  21. Pasculle A. W., Dowling J. N., Frola F. N., McDevitt D. A., Levi M. A. Antimicrobial therapy of experimental Legionella micdadei pneumonia in guinea pigs. Antimicrob Agents Chemother. 1985 Dec;28(6):730–734. doi: 10.1128/aac.28.6.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pohlod D. J., Saravolatz L. D., Quinn E. L., Somerville M. M. Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila. Antimicrob Agents Chemother. 1980 Aug;18(2):353–354. doi: 10.1128/aac.18.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramirez J. A., Summersgill J. T., Miller R. D., Meyers T. L., Raff M. J. Bactericidal activity of imipenem compared to erythromycin against intracellular Legionella pneumophila. Drugs Exp Clin Res. 1992;18(10):407–410. [PubMed] [Google Scholar]
  24. Ramirez J. A., Summersgill J. T., Miller R. D., Meyers T. L., Raff M. J. Comparative study of the bactericidal activity of ampicillin/sulbactam and erythromycin against intracellular Legionella pneumophila. J Antimicrob Chemother. 1993 Jul;32(1):93–99. doi: 10.1093/jac/32.1.93. [DOI] [PubMed] [Google Scholar]
  25. Ruckdeschel G., Ehret W., Ahl A. Susceptibility of Legionella spp. to imipenem and 27 other beta-lactam antibiotics. Eur J Clin Microbiol. 1984 Oct;3(5):463–467. doi: 10.1007/BF02017376. [DOI] [PubMed] [Google Scholar]
  26. Schwab J. C., Mandell G. L. The importance of penetration of antimicrobial agents into cells. Infect Dis Clin North Am. 1989 Sep;3(3):461–467. [PubMed] [Google Scholar]
  27. Smith G. M., Abbott K. H., Sutherland R. Bactericidal effects of co-amoxiclav (amoxycillin clavulanic acid) against a Legionella pneumophila pneumonia in the immunocompromised weanling rat. J Antimicrob Chemother. 1992 Oct;30(4):525–534. doi: 10.1093/jac/30.4.525. [DOI] [PubMed] [Google Scholar]
  28. Smith G. M., Abbott K. H., Wilkinson M. J., Beale A. S., Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against a Legionella pneumophila pneumonia in the weanling rat. J Antimicrob Chemother. 1991 Jan;27(1):127–136. doi: 10.1093/jac/27.1.127. [DOI] [PubMed] [Google Scholar]
  29. Smith G. M., Abbott K. H., Wilkinson M. J., Beale A. S., Sutherland R. Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats. Antimicrob Agents Chemother. 1991 Jul;35(7):1423–1429. doi: 10.1128/aac.35.7.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith G. M., Sutherland R. Activity of amoxycillin-clavulanic acid against Legionella pneumophila in vitro and in an experimental respiratory infection model. J Hosp Infect. 1992 Nov;22 (Suppl A):61–67. doi: 10.1016/s0195-6701(05)80008-8. [DOI] [PubMed] [Google Scholar]
  31. Staikowsky F., Haziza F., Guidet B., Vassal T., Offenstadt G. Accès de torsades de pointes au cours d'une maladie des légionnaires:un accident exceptionnel de l'érythromycine. Rev Pneumol Clin. 1991;47(2):92–94. [PubMed] [Google Scholar]
  32. Stokes D. H., Slocombe B., Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against Legionella pneumophila. J Antimicrob Chemother. 1989 Jan;23(1):43–51. doi: 10.1093/jac/23.1.43. [DOI] [PubMed] [Google Scholar]
  33. Stokes D. H., Wilkinson M. J., Tyler J., Slocombe B., Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against intracellular Legionella pneumophila in tissue culture studies. J Antimicrob Chemother. 1989 Apr;23(4):547–556. doi: 10.1093/jac/23.4.547. [DOI] [PubMed] [Google Scholar]
  34. Toro J., Sawatari K., Kanda T., Saito A., Hara K. New beta-lactamase-resistant cephem treatment of guinea pigs infected with Legionella pneumophila. Microbiol Immunol. 1983;27(8):649–654. doi: 10.1111/j.1348-0421.1983.tb00627.x. [DOI] [PubMed] [Google Scholar]
  35. Tulkens P. M. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):100–106. doi: 10.1007/BF01964420. [DOI] [PubMed] [Google Scholar]
  36. Vildé J. L., Dournon E., Rajagopalan P. Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents. Antimicrob Agents Chemother. 1986 Nov;30(5):743–748. doi: 10.1128/aac.30.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van den Broek P. J. Antimicrobial drugs, microorganisms, and phagocytes. Rev Infect Dis. 1989 Mar-Apr;11(2):213–245. doi: 10.1093/clinids/11.2.213. [DOI] [PubMed] [Google Scholar]

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