Abstract
Combination antimicrobial therapy against Legionella species has not been well studied. Several quinolones have activity against Legionella strains, which prompted this in vitro search for a synergistic combination with the macrolides. By a checkerboard assay, erythromycin, clarithromycin, and azithromycin, each in combination with ciprofloxacin and levofloxacin, were tested for synergy against 46 isolates of Legionella. The agar dilution method was employed using buffered charcoal-yeast extract media. A final inoculum of 10(4) CFU per spot was prepared from 24-h growth of each isolate. Plates were incubated at 35 degrees C for 48 h. Synergy, partial synergy, additive effect, or indifference was observed for all combinations of antibiotics tested. There was no antagonism observed. Synergy occurred to a significantly greater extent for the clarithromycin-levofloxacin (P = 0.0001) and azithromycin-levofloxacin (P = 0.003) combinations versus erythromycin-levofloxacin. The azithromycin-ciprofloxacin combination demonstrated significantly greater synergy than did either erythromycin-ciprofloxacin (P = 0.003) or clarithromycin-ciprofloxacin (P = 0.001). The newer macrolides clarithromycin and azithromycin may be more active in combination with a fluoroquinolone than is erythromycin.
Full Text
The Full Text of this article is available as a PDF (212.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bornstein N., Roudier C., Fleurette J. Determination of the activity on Legionella of eight macrolides and related agents by comparative testing on three media. J Antimicrob Chemother. 1985 Jan;15(1):17–22. doi: 10.1093/jac/15.1.17. [DOI] [PubMed] [Google Scholar]
- 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]
- Gooding B. B., Erwin M. E., Barrett M. S., Johnson D. M., Jones R. N. Antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) against over 100 Legionella sp. isolates. Antimicrob Agents Chemother. 1992 Sep;36(9):2049–2050. doi: 10.1128/aac.36.9.2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardy D. J., Hensey D. M., Beyer J. M., Vojtko C., McDonald E. J., Fernandes P. B. Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides. Antimicrob Agents Chemother. 1988 Nov;32(11):1710–1719. doi: 10.1128/aac.32.11.1710. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones R. N. Activity of sparfloxacin (AT-4140), PD127391 and PD131628 against Legionella spp. J Antimicrob Chemother. 1991 Mar;27(3):389–390. doi: 10.1093/jac/27.3.389. [DOI] [PubMed] [Google Scholar]
- Jones R. N., Erwin M. E., Barrett M. S. In vitro activity of clarithromycin (TE-031, A-67268) and 14OH-clarithromycin alone and in combination against Legionella species. Eur J Clin Microbiol Infect Dis. 1990 Nov;9(11):846–848. doi: 10.1007/BF01967390. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Salord J. M., Matsiota-Bernard P., Staïkowsky F., Kirstetter M., Frottier J., Nauciel C. Unsuccessful treatment of Legionella pneumophila infection with a fluoroquinolone. Clin Infect Dis. 1993 Sep;17(3):518–519. doi: 10.1093/clinids/17.3.518. [DOI] [PubMed] [Google Scholar]
- Unertl K. E., Lenhart F. P., Forst H., Vogler G., Wilm V., Ehret W., Ruckdeschel G. Ciprofloxacin in the treatment of legionellosis in critically ill patients including those cases unresponsive to erythromycin. Am J Med. 1989 Nov 30;87(5A):128S–131S. doi: 10.1016/0002-9343(89)90041-7. [DOI] [PubMed] [Google Scholar]