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. 1994 Jun;38(6):1433–1438. doi: 10.1128/aac.38.6.1433

Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex.

N Rastogi 1, K S Goh 1, A Bryskier 1
PMCID: PMC188227  PMID: 8092850

Abstract

Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens such as M. chelonae and M. fortuitum. In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clofazimine for 10 clinical isolates of the M. avium complex (5 each from human immunodeficiency virus [HIV]-positive and HIV-negative patients) were determined. Roxithromycin MICs against all the isolates were below the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4. In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels. Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol, in 3 strains each by rifampin and clofazimine, in 2 strains by amikacin, and in 1 strain by ofloxacin. In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened.

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Selected References

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  1. Agins B. D., Berman D. S., Spicehandler D., el-Sadr W., Simberkoff M. S., Rahal J. J. Effect of combined therapy with ansamycin, clofazimine, ethambutol, and isoniazid for Mycobacterium avium infection in patients with AIDS. J Infect Dis. 1989 Apr;159(4):784–787. doi: 10.1093/infdis/159.4.784. [DOI] [PubMed] [Google Scholar]
  2. Baron E. J., Young L. S. Amikacin, ethambutol, and rifampin for treatment of disseminated Mycobacterium avium-intracellulare infections in patients with acquired immune deficiency syndrome. Diagn Microbiol Infect Dis. 1986 Sep;5(3):215–220. doi: 10.1016/0732-8893(86)90004-0. [DOI] [PubMed] [Google Scholar]
  3. Chiu J., Nussbaum J., Bozzette S., Tilles J. G., Young L. S., Leedom J., Heseltine P. N., McCutchan J. A. Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. California Collaborative Treatment Group. Ann Intern Med. 1990 Sep 1;113(5):358–361. doi: 10.7326/0003-4819-113-5-358. [DOI] [PubMed] [Google Scholar]
  4. Crowle A. J., Dahl R., Ross E., May M. H. Evidence that vesicles containing living, virulent Mycobacterium tuberculosis or Mycobacterium avium in cultured human macrophages are not acidic. Infect Immun. 1991 May;59(5):1823–1831. doi: 10.1128/iai.59.5.1823-1831.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Etzkorn E. T., Aldarondo S., McAllister C. K., Matthews J., Ognibene A. J. Medical therapy of Mycobacterium avium-intracellulare pulmonary disease. Am Rev Respir Dis. 1986 Sep;134(3):442–445. doi: 10.1164/arrd.1986.134.3.442. [DOI] [PubMed] [Google Scholar]
  6. Heifets L. B., Lindholm-Levy P. J., Comstock R. D. Clarithromycin minimal inhibitory and bactericidal concentrations against Mycobacterium avium. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856–858. doi: 10.1164/ajrccm/145.4_Pt_1.856. [DOI] [PubMed] [Google Scholar]
  7. Hoy J., Mijch A., Sandland M., Grayson L., Lucas R., Dwyer B. Quadruple-drug therapy for Mycobacterium avium-intracellulare bacteremia in AIDS patients. J Infect Dis. 1990 Apr;161(4):801–805. doi: 10.1093/infdis/161.4.801. [DOI] [PubMed] [Google Scholar]
  8. Rastogi N., Frehel C., Ryter A., Ohayon H., Lesourd M., David H. L. Multiple drug resistance in Mycobacterium avium: is the wall architecture responsible for exclusion of antimicrobial agents? Antimicrob Agents Chemother. 1981 Nov;20(5):666–677. doi: 10.1128/aac.20.5.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rastogi N., Goh K. S., Bryskier A. In vitro activity of roxithromycin against 16 species of atypical mycobacteria and effect of pH on its radiometric MICs. Antimicrob Agents Chemother. 1993 Jul;37(7):1560–1562. doi: 10.1128/aac.37.7.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rastogi N., Goh K. S., David H. L. Enhancement of drug susceptibility of Mycobacterium avium by inhibitors of cell envelope synthesis. Antimicrob Agents Chemother. 1990 May;34(5):759–764. doi: 10.1128/aac.34.5.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rastogi N., Goh K. S. Effect of pH on radiometric MICs of clarithromycin against 18 species of mycobacteria. Antimicrob Agents Chemother. 1992 Dec;36(12):2841–2842. doi: 10.1128/aac.36.12.2841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rastogi N., Goh K. S., Guillou N., Labrousse V. Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs? Zentralbl Bakteriol. 1992 Dec;277(4):474–484. doi: 10.1016/s0934-8840(11)80472-x. [DOI] [PubMed] [Google Scholar]
  13. Rastogi N., Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother. 1991 Mar;35(3):462–470. doi: 10.1128/aac.35.3.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rastogi N., Labrousse V., Goh K. S., De Sousa J. P. Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages. Antimicrob Agents Chemother. 1991 Dec;35(12):2473–2480. doi: 10.1128/aac.35.12.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rastogi N., McFadden J. J. Mycobacteria and AIDS: epidemiological and genetic markers, virulence factors and interactions with the immune system. Res Microbiol. 1992 May;143(4):361–362. doi: 10.1016/0923-2508(92)90046-q. [DOI] [PubMed] [Google Scholar]
  16. Rastogi N., Ross B. C., Dwyer B., Goh K. S., Clavel-Sérès S., Jeantils V., Cruaud P. Emergence during unsuccessful chemotherapy of multiple drug resistance in a strain of Mycobacterium tuberculosis. Eur J Clin Microbiol Infect Dis. 1992 Oct;11(10):901–907. doi: 10.1007/BF01962370. [DOI] [PubMed] [Google Scholar]
  17. Stauffer F., Dörtbudak O., Lahonik E. In vitro testing of clarithromycin in combination with ethambutol and rifampicin against Mycobacterium avium complex. Infection. 1991 Sep-Oct;19(5):343–345. doi: 10.1007/BF01645362. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Yajko D. M. In vitro activity of antimicrobial agents against the Mycobacterium avium complex inside macrophages from HIV1-infected individuals: the link to clinical response to treatment? Res Microbiol. 1992 May;143(4):411–419. doi: 10.1016/0923-2508(92)90055-s. [DOI] [PubMed] [Google Scholar]

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