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. 1995 Aug;39(8):1661–1666. doi: 10.1128/aac.39.8.1661

Inhibitory and bactericidal activities of levofloxacin, ofloxacin, erythromycin, and rifampin used singly and in combination against Legionella pneumophila.

A L Baltch 1, R P Smith 1, W Ritz 1
PMCID: PMC162803  PMID: 7486896

Abstract

The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were studied with buffered charcoal yeast extract (BCYE) agar (inoculum, 10(4) CFU per spot), and the susceptibilities of five isolates were studied with buffered yeast extract (BYE) broth (inoculum, 10(5) CFU/ml). The MICs inhibiting 90% of strains tested on BCYE agar were 0.125, 0.25, 1.0, and < or = 0.004 micrograms/ml for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MICs by the BYE broth dilution method were 1 to 3, 2, 1 to 2, and 1 tube lower than those by the agar dilution method for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MBCs were 1 to 2 tubes higher than the broth dilution MICs for levofloxacin, 1 to 3 tubes higher than the broth dilution MICs for ofloxacin, 1 to 3 tubes higher than the broth dilution MICs for erythromycin, and the same as the broth dilution MICs for rifampin. In kinetic time-kill curve studies, at drug concentrations of 1.0 and 2.0 times the MIC, the most active drugs were levofloxacin and rifampin. At 72 h, concentrations of levofloxacin and rifampin of 2.0 times the MIC demonstrated a bactericidal effect against L. pneumophila. In contrast, at concentrations of 1.0 and 2.0 times the MICs regrowth was observed with ofloxacin and only a gradual decrease in the numbers of CFU per milliliter was observed with erythromycin. Only a minor inhibitory effect was observed with 0.25 or 0.5 time the MICs of all drugs at 24 to 48 h, with regrowth occurring at 72 h. In contrast to erythromycin or ofloxacin plus rifampin at 0.25 time the MICs, only levofloxacin plus rifampin demonstrated synergy. Thus, levofloxacin demonstrated the best inhibitory and bactericidal effects against L. pneumophila when it was studied alone or in a combination with rifampin.

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Selected References

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  1. Bacheson M. A., Friedman H. M., Benson C. E. Antimicrobial susceptibility of intracellular Legionella pneumophila. Antimicrob Agents Chemother. 1981 Nov;20(5):691–692. doi: 10.1128/aac.20.5.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barker J. E., Farrell I. D. The effects of single and combined antibiotics on the growth of Legionella pneumophila using time-kill studies. J Antimicrob Chemother. 1990 Jul;26(1):45–53. doi: 10.1093/jac/26.1.45. [DOI] [PubMed] [Google Scholar]
  3. Chen S. C., Paul M. L., Gilbert G. L. Susceptibility of Legionella species to antimicrobial agents. Pathology. 1993 Apr;25(2):180–183. doi: 10.3109/00313029309084795. [DOI] [PubMed] [Google Scholar]
  4. Cherubin C. E., Eng R. H., Smith S. M., Tan E. N. A comparison of antimicrobial activity of ofloxacin, L-ofloxacin, and other oral agents for respiratory pathogens. Diagn Microbiol Infect Dis. 1992 Feb;15(2):141–144. doi: 10.1016/0732-8893(92)90038-u. [DOI] [PubMed] [Google Scholar]
  5. Collins L. A., Wennersten C. B., Ferraro M. J., Moellering R. C., Jr, Eliopoulos G. M. Comparative activities of piperacillin and tazobactam against clinical isolates of Legionella spp. Antimicrob Agents Chemother. 1994 Jan;38(1):144–146. doi: 10.1128/aac.38.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dubois J., Joly J. R. In vitro activity of lomefloxacin (SC 47111 or NY-198) against isolates of Legionella spp. Diagn Microbiol Infect Dis. 1989 May-Jun;12(3 Suppl):89S–91S. doi: 10.1016/0732-8893(89)90073-4. [DOI] [PubMed] [Google Scholar]
  7. Edelstein P. H., Edelstein M. A. In vitro activity of azithromycin against clinical isolates of Legionella species. Antimicrob Agents Chemother. 1991 Jan;35(1):180–181. doi: 10.1128/aac.35.1.180. [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., Gaudet E. A., Edelstein M. A. In vitro activity of lomefloxacin (NY-198 or SC 47111), ciprofloxacin, and erythromycin against 100 clinical Legionella strains. Diagn Microbiol Infect Dis. 1989 May-Jun;12(3 Suppl):93S–95S. doi: 10.1016/0732-8893(89)90074-6. [DOI] [PubMed] [Google Scholar]
  10. Edelstein P. H. Legionnaires' disease. Clin Infect Dis. 1993 Jun;16(6):741–747. doi: 10.1093/clind/16.6.741. [DOI] [PubMed] [Google Scholar]
  11. Edelstein P. H. Rifampin resistance of Legionella pneumophila is not increased during therapy for experimental Legionnaires disease: study of rifampin resistance using a guinea pig model of Legionnaires disease. Antimicrob Agents Chemother. 1991 Jan;35(1):5–9. doi: 10.1128/aac.35.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fu K. P., Foleno B., Rosenthale M. E. The postantibiotic suppressive effect of L-ofloxacin, an optically active isomer of ofloxacin. Diagn Microbiol Infect Dis. 1992 May-Jun;15(4):375–378. doi: 10.1016/0732-8893(92)90028-r. [DOI] [PubMed] [Google Scholar]
  13. Fu K. P., Lafredo S. C., Foleno B., Isaacson D. M., Barrett J. F., Tobia A. J., Rosenthale M. E. In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin. Antimicrob Agents Chemother. 1992 Apr;36(4):860–866. doi: 10.1128/aac.36.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Furneri P. M., Bazzano M., Campo L., Cesana M., Tempera G. In vitro activity of rufloxacin against Listeria monocytogenes, Legionella pneumophila, and Chlamydia trachomatis. Chemotherapy. 1994 Mar-Apr;40(2):104–108. doi: 10.1159/000239180. [DOI] [PubMed] [Google Scholar]
  15. Gump D. W., Frank R. O., Winn W. C., Jr, Foster R. S., Jr, Broome C. V., Cherry W. B. Legionnaires' disease in patients with associated serious disease. Ann Intern Med. 1979 Apr;90(4):538–542. doi: 10.7326/0003-4819-90-4-538. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Higa F., Saito A., Inadome J., Kusano N., Kitsukawa K. Influence of methylprednisolone on the intracellular antimicrobial activity of erythromycin and clindamycin against Legionella pneumophila. J Antimicrob Chemother. 1993 Jun;31(6):901–908. doi: 10.1093/jac/31.6.901. [DOI] [PubMed] [Google Scholar]
  18. Hohl P., von Graevenitz A., Zollinger-Iten J. Fleroxacin (Ro 23-6240): activity in vitro against 355 enteropathogenic and non-fermentative gram-negative bacilli and Legionella pneumophila. J Antimicrob Chemother. 1987 Sep;20(3):373–378. doi: 10.1093/jac/20.3.373. [DOI] [PubMed] [Google Scholar]
  19. Hohl P., von Graevenitz A., Zollinger-Iten J. In vitro activity of carumonam (Ro 17-2301; AMA-1080) versus enteropathogenic and nonfermentative gram-negative rods and Legionella pneumophila. Antimicrob Agents Chemother. 1988 Oct;32(10):1593–1594. doi: 10.1128/aac.32.10.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones R. N., Barry A. L. Antimicrobial activity of imipenem and SCH34343 against Legionella species. Diagn Microbiol Infect Dis. 1987 Apr;6(4):307–309. doi: 10.1016/0732-8893(87)90180-5. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Liebers D. M., Baltch A. L., Smith R. P., Hammer M. C., Conroy J. V. Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions. J Antimicrob Chemother. 1989 Jan;23(1):37–41. doi: 10.1093/jac/23.1.37. [DOI] [PubMed] [Google Scholar]
  24. Marshall A. J., Piddock L. J. Interaction of divalent cations, quinolones and bacteria. J Antimicrob Chemother. 1994 Oct;34(4):465–483. doi: 10.1093/jac/34.4.465. [DOI] [PubMed] [Google Scholar]
  25. Moffie B. G., Mouton R. P. Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics. J Antimicrob Chemother. 1988 Oct;22(4):457–462. doi: 10.1093/jac/22.4.457. [DOI] [PubMed] [Google Scholar]
  26. Morley J. N., Smith L. C., Baltch A. L., Smith R. P. Recurrent infection due to Legionella pneumophila in a patient with AIDS. Clin Infect Dis. 1994 Dec;19(6):1130–1132. doi: 10.1093/clinids/19.6.1130. [DOI] [PubMed] [Google Scholar]
  27. Nguyen M. H., Stout J. E., Yu V. L. Legionellosis. Infect Dis Clin North Am. 1991 Sep;5(3):561–584. [PubMed] [Google Scholar]
  28. Parker M. M., Macher A. M., Shelhamer J. H., Balow J. E., Gill V., Parrillo J. E. Unresponsiveness of Legionella bozemanii pneumonia to erythromycin administration despite in vitro sensitivity. Am Rev Respir Dis. 1983 Nov;128(5):955–956. doi: 10.1164/arrd.1983.128.5.955. [DOI] [PubMed] [Google Scholar]
  29. Rajagopalan-Levasseur P., Dournon E., Dameron G., Vilde J. L., Pocidalo J. J. Comparative postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against intracellular multiplication of Legionella pneumophila serogroup 1. Antimicrob Agents Chemother. 1990 Sep;34(9):1733–1738. doi: 10.1128/aac.34.9.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reda C., Quaresima T., Pastoris M. C. In-vitro activity of six intracellular antibiotics against Legionella pneumophila strains of human and environmental origin. J Antimicrob Chemother. 1994 Apr;33(4):757–764. doi: 10.1093/jac/33.4.757. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Soussy C. J., Acar J. F., Cluzel R., Courvalin P., Duval J., Fleurette J., Megraud F., Meyran M., Thabaut A. A collaborative study of the in-vitro sensitivity to RP 59500 of bacteria isolated in seven hospitals in France. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):53–58. doi: 10.1093/jac/30.suppl_a.53. [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. Takasuna K., Kasai Y., Usui C., Takahashi M., Hirohashi M., Tamura K., Takayama S. General pharmacology of the new quinolone antibacterial agent levofloxacin. Arzneimittelforschung. 1992 Mar;43(3A):408–418. [PubMed] [Google Scholar]
  35. 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]
  36. Zanetti S., Ungheri D., Castellani Pastoris M., Fadda G. Comparative in vitro susceptibility studies of FCE 22250 and rifampicin on Legionella and Chlamydia trachomatis strains. Drugs Exp Clin Res. 1987;13(10):631–634. [PubMed] [Google Scholar]

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