Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1987 Oct;31(10):1529–1534. doi: 10.1128/aac.31.10.1529

Effect of quinolones and other antimicrobial agents on cell-associated Legionella pneumophila.

D Havlichek 1, L Saravolatz 1, D Pohlod 1
PMCID: PMC174984  PMID: 3435101

Abstract

We evaluated the in vitro susceptibility of Legionella pneumophila ATCC 33152 (serogroup I) to 13 antibiotics alone and in combination with rifampin (0.1 mg/liter) by three methods. Extracellular susceptibility was determined by MIC determinations and time kill curves in buffered yeast extract broth, while intracellular susceptibility was determined by peripheral human monocytes in RPMI 1640 culture medium. Antibiotic concentrations equal to or greater than the broth dilution MIC inhibited or killed L. pneumophila by the time kill method, except this was not the case for trimethoprim-sulfamethoxazole. Antibiotic concentrations below the broth dilution MIC did not inhibit Legionella growth. The only antibiotic-rifampin combinations which produced improved killing of L. pneumophila by the time kill method were those in which the logarithmic growth of L. pneumophila occurred during the experiment (rosoxacin, amifloxacin, cinoxacin, trimethoprim-sulfamethoxazole, clindamycin, and doxycycline). Neither direct MICs nor time kill curve assays accurately predicted intracellular L. pneumophila susceptibility. Rifampin, erythromycin, ciprofloxacin, rosoxacin, enoxacin, amifloxacin, gentamicin, clindamycin, and doxycycline all inhibited intracellular L. pneumophila growth at readily achievable concentrations in serum. Cefoxitin and thienamycin showed no inhibition of growth, although they were present extracellularly at concentrations that were 20 to 1,000 times their broth dilution MICs. Clindamycin was the only antibiotic that was able to inhibit intracellular L. pneumophila growth at an extracellular concentration below its MIC. The gentamicin (5 mg/liter)-rifampin combination was the only antibiotic-rifampin combination which demonstrated decreased cell-associated Legionella survival in this model of in vitro susceptibility.

Full text

PDF
1529

Selected References

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

  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. De Simone C., Baldinelli L., Ferrazzi M., De Santis S., Pugnaloni L., Sorice F. Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and pipemidic acid on human gamma-interferon production and blastogenesis. J Antimicrob Chemother. 1986 Jun;17(6):811–814. doi: 10.1093/jac/17.6.811. [DOI] [PubMed] [Google Scholar]
  3. Desnottes J. F., Jacotot F., Bruel J., Bassoullet M. T., Niel G. Effects of pefloxacin on phagocytosis function of rat macrophages and polymorphonuclear leucocytes. J Antimicrob Chemother. 1986 Apr;17 (Suppl B):53–57. doi: 10.1093/jac/17.suppl_b.53. [DOI] [PubMed] [Google Scholar]
  4. Easmon C. S., Crane J. P. Uptake of ciprofloxacin by macrophages. J Clin Pathol. 1985 Apr;38(4):442–444. doi: 10.1136/jcp.38.4.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Fitzgeorge R. B., Gibson D. H., Jepras R., Baskerville A. Studies on ciprofloxacin therapy of experimental Legionnaires' disease. J Infect. 1985 May;10(3):194–203. doi: 10.1016/s0163-4453(85)92438-7. [DOI] [PubMed] [Google Scholar]
  8. Fitzgeorge R. B. The effect of antibiotics on the growth of Legionella pneumophila in guinea-pig alveolar phagocytes infected in vivo by an aerosol. J Infect. 1985 May;10(3):189–193. doi: 10.1016/s0163-4453(85)92413-2. [DOI] [PubMed] [Google Scholar]
  9. Fraser D. W., Tsai T. R., Orenstein W., Parkin W. E., Beecham H. J., Sharrar R. G., Harris J., Mallison G. F., Martin S. M., McDade J. E. Legionnaires' disease: description of an epidemic of pneumonia. N Engl J Med. 1977 Dec 1;297(22):1189–1197. doi: 10.1056/NEJM197712012972201. [DOI] [PubMed] [Google Scholar]
  10. Fraser D. W., Wachsmuth I., Bopp C., Feeley J. C., Tsai T. F. Antibiotic treatment of guinea-pigs infected with agent of Legionnaires' disease. Lancet. 1978 Jan 28;1(8057):175–178. doi: 10.1016/s0140-6736(78)90611-6. [DOI] [PubMed] [Google Scholar]
  11. Gmünder F. K., Seger R. A. Chronic granulomatous disease: mode of action of sulfamethoxazole/trimethoprim. Pediatr Res. 1981 Dec;15(12):1533–1537. doi: 10.1203/00006450-198112000-00017. [DOI] [PubMed] [Google Scholar]
  12. Gollapudi S. V., Vayuvegula B., Gupta S., Fok M., Thadepalli H. Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen-induced human mononuclear cell proliferation. Antimicrob Agents Chemother. 1986 Sep;30(3):390–394. doi: 10.1128/aac.30.3.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodhart G. L. Effect of aminoglycosides on the chemotactic response of human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1977 Oct;12(4):540–542. doi: 10.1128/aac.12.4.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hand W. L., Corwin R. W., Steinberg T. H., Grossman G. D. Uptake of antibiotics by human alveolar macrophages. Am Rev Respir Dis. 1984 Jun;129(6):933–937. doi: 10.1164/arrd.1984.129.6.933. [DOI] [PubMed] [Google Scholar]
  15. Horwitz M. A., Silverstein S. C. Activated human monocytes inhibit the intracellular multiplication of Legionnaires' disease bacteria. J Exp Med. 1981 Nov 1;154(5):1618–1635. doi: 10.1084/jem.154.5.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Horwitz M. A., Silverstein S. C. Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin. J Clin Invest. 1983 Jan;71(1):15–26. doi: 10.1172/JCI110744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Horwitz M. A., Silverstein S. C. Legionnaires' disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes. J Clin Invest. 1980 Sep;66(3):441–450. doi: 10.1172/JCI109874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jacobs R. F., Locksley R. M., Wilson C. B., Haas J. E., Klebanoff S. J. Interaction of primate alveolar macrophages and Legionella pneumophila. J Clin Invest. 1984 Jun;73(6):1515–1523. doi: 10.1172/JCI111357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnson J. D., Hand W. L., Francis J. B., King-Thompson N., Corwin R. W. Antibiotic uptake by alveolar macrophages. J Lab Clin Med. 1980 Mar;95(3):429–439. [PubMed] [Google Scholar]
  20. Meyer R. D. Legionella infections: a review of five years of research. Rev Infect Dis. 1983 Mar-Apr;5(2):258–278. doi: 10.1093/clinids/5.2.258. [DOI] [PubMed] [Google Scholar]
  21. Nash T. W., Libby D. M., Horwitz M. A. Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J Clin Invest. 1984 Sep;74(3):771–782. doi: 10.1172/JCI111493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Saito A., Sawatari K., Fukuda Y., Nagasawa M., Koga H., Tomonaga A., Nakazato H., Fujita K., Shigeno Y., Suzuyama Y. Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs. Antimicrob Agents Chemother. 1985 Jul;28(1):15–20. doi: 10.1128/aac.28.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Wolfson J. S., Hooper D. C. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985 Oct;28(4):581–586. doi: 10.1128/aac.28.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yoshida S., Mizuguchi Y. Antibiotic susceptibility of Legionella pneumophia Philadelphia-1 in cultured guinea-pig peritoneal macrophages. J Gen Microbiol. 1984 Apr;130(4):901–906. doi: 10.1099/00221287-130-4-901. [DOI] [PubMed] [Google Scholar]

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

RESOURCES