Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1988 Sep;32(9):1392–1395. doi: 10.1128/aac.32.9.1392

Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

D M Yajko 1, J Kirihara 1, C Sanders 1, P Nassos 1, W K Hadley 1
PMCID: PMC175874  PMID: 3196000

Abstract

Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.

Full text

PDF
1392

Selected References

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

  1. Armstrong D., Gold J. W., Dryjanski J., Whimbey E., Polsky B., Hawkins C., Brown A. E., Bernard E., Kiehn T. E. Treatment of infections in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):738–743. doi: 10.7326/0003-4819-103-5-738. [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. Berenbaum M. C. A method for testing for synergy with any number of agents. J Infect Dis. 1978 Feb;137(2):122–130. doi: 10.1093/infdis/137.2.122. [DOI] [PubMed] [Google Scholar]
  4. Hallander H. O., Dornbusch K., Gezelius L., Jacobson K., Karlsson I. Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method. Antimicrob Agents Chemother. 1982 Nov;22(5):743–752. doi: 10.1128/aac.22.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Hoffner S. E., Svenson S. B., Källenius G. Synergistic effects of antimycobacterial drug combinations on Mycobacterium avium complex determined radiometrically in liquid medium. Eur J Clin Microbiol. 1987 Oct;6(5):530–535. doi: 10.1007/BF02014241. [DOI] [PubMed] [Google Scholar]
  7. Horsburgh C. R., Jr, Cohn D. L., Roberts R. B., Masur H., Miller R. A., Tsang A. Y., Iseman M. D. Mycobacterium avium-M. intracellulare isolates from patients with or without acquired immunodeficiency syndrome. Antimicrob Agents Chemother. 1986 Dec;30(6):955–957. doi: 10.1128/aac.30.6.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kiehn T. E., Edwards F. F., Brannon P., Tsang A. Y., Maio M., Gold J. W., Whimbey E., Wong B., McClatchy J. K., Armstrong D. Infections caused by Mycobacterium avium complex in immunocompromised patients: diagnosis by blood culture and fecal examination, antimicrobial susceptibility tests, and morphological and seroagglutination characteristics. J Clin Microbiol. 1985 Feb;21(2):168–173. doi: 10.1128/jcm.21.2.168-173.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Masur H., Tuazon C., Gill V., Grimes G., Baird B., Fauci A. S., Lane H. C. Effect of combined clofazimine and ansamycin therapy on Mycobacterium avium-Mycobacterium intracellulare bacteremia in patients with AIDS. J Infect Dis. 1987 Jan;155(1):127–129. doi: 10.1093/infdis/155.1.127. [DOI] [PubMed] [Google Scholar]
  10. Wollschlager C. M., Khan F. A., Chitkara R. K., Shivaram U. Pulmonary manifestations of the acquired immunodeficiency syndrome (AIDS). Chest. 1984 Feb;85(2):197–202. doi: 10.1378/chest.85.2.197. [DOI] [PubMed] [Google Scholar]
  11. Woods G. L., Washington J. A., 2nd Mycobacteria other than Mycobacterium tuberculosis: review of microbiologic and clinical aspects. Rev Infect Dis. 1987 Mar-Apr;9(2):275–294. doi: 10.1093/clinids/9.2.275. [DOI] [PubMed] [Google Scholar]
  12. Yajko D. M., Nassos P. S., Hadley W. K. Broth microdilution testing of susceptibilities to 30 antimicrobial agents of Mycobacterium avium strains from patients with acquired immune deficiency syndrome. Antimicrob Agents Chemother. 1987 Oct;31(10):1579–1584. doi: 10.1128/aac.31.10.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Yajko D. M., Nassos P. S., Hadley W. K. Therapeutic implications of inhibition versus killing of Mycobacterium avium complex by antimicrobial agents. Antimicrob Agents Chemother. 1987 Jan;31(1):117–120. doi: 10.1128/aac.31.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zimmer B. L., DeYoung D. R., Roberts G. D. In vitro synergistic activity of ethambutol, isoniazid, kanamycin, rifampin, and streptomycin against Mycobacterium avium-intracellulare complex. Antimicrob Agents Chemother. 1982 Jul;22(1):148–150. doi: 10.1128/aac.22.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES