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Journal of Antimicrobial Chemotherapy (1996) 37, 501-510
© 1996 The British Society for Antimicrobial Chemotherapy

research-article

Activity of rifabutin, clarithromycin, ethambutol, sparfloxacin and amikacin, alone and in combination, against Mycobacterium avium complex in human macrophages

Isabelle Pellegrina, Jeanne Maugeina, Catherine Lapeyrea, Pascal Barbeaub, Bernard Lengb and Jean-Luc Pellegrinb,*

aLaboratoire de Bactériologie, Hôpital Haut-Léveque (CHR Bordeaux) 33604 Pessac, France bClinique de Médecine Interne et Maladies Infectieuses, Hôpital Haut-Léveque (CHR Bordeaux) 33604 Pessac, France

Received 11 July 1995; returned 4 September 1995; accepted 11 October 1995

*Corresponding author

Disseminated infection with Mycobacterium avium complex (MAC) in patients with AIDS is currently treated with a combination of antimycobacterial agents in order to prevent the selection of resistant mutant strains. Although clinical and microbiological responses can generally be achieved within a few weeks, relapses are common and require modification of the combination regimen or identification of effective alternate therapies. In this study we investigated the activities of rifabutin 0.5 mg/L, sparfloxacin 1 mg/L, clarithromycin 4 mg/L, amikacin 16mg/L and ethambutol 2 mg/L, alone and in combination, against nine strains of M. avium isolated from the blood of patients with AIDS in order to identify regimens with the greatest therapeutic potential. Macrophages derived from human monocytes were infected with M. avium and inoculated with a single drug or a combination of drugs; cfu counts were performed at 0, 4 and 7 days after infection. At day 4 and at day 7, the combination of rifabutin, clarithromycin, amikacin and sparfloxacin displayed the highest degree of activity. However, the activity did not differ significantly from that of the combination of rifabutin, clarithromycin and ethambutol. The results of this study confirm the activity of combinations including rifabutin and clarithromycin (± ethambutol) in human monocyte-derived macrophages and suggest potentially useful associations in incorporating sparfloxacin and amikacin.


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