a Service des Maladies Infectieuses et Tropicales, Hôpital de lArchet I, BP 79, 06202 Nice cedex 3; b Laboratoires Marcel Mérieux, BP 7322, 69357 Lyon cedex 07, France
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Abstract |
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Introduction |
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Materials and methods |
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Results |
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Antibacterial efficacy is shown in the Table. All patients but one with associated highly active antiretroviral therapy (HAART) had a CD4 % T-cell count recovery of <150/µL. Duration of parenteral therapy was 29 ± 13 days according to tolerance and patients request. After parenteral therapy, treatment consisted of a macrolide plus ethambutol in 11 cases and a macrolide plus ciprofloxacin in one case of intolerance to ethambutol. Eleven patients (73%) had negative blood cultures by the end of the first 2 weeks of treatment and 13/15 (86%) patients achieved negative blood cultures by the end of their parenteral therapy. No catheter-related complications were observed. Five patients had adverse effects during the period of clinical follow-up that resulted in therapeutic discontinuation (one cutaneous allergy and one digestive adverse effect with clarithromycin; one altered colour vision with ethambutol; one serum creatinine increase with amikacin and one thrombocytopenia with ciprofloxacin). All adverse effects resolved after drug discontinuation. Four relapses were diagnosed at days 60, 105, 160 and 330. The median survival time was 12 ± 10 months (range 1-30 months) and 10 patients died during the study period.
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Discussion |
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Our study shows that the combination of an initial parenteral regimen with a macrolide for therapy of disseminated MAC infection results in early mycobacterial blood culture negativity, in 11/15 cases in <2 weeks of treatment. In another pilot study using oral clarithromycin and ciprofloxacin plus parenteral amikacin (7.5 mg/kg/day), the first negative culture was obtained within 4.3 ± 1.4 weeks. 6 Chiu et al. 3 reported resolution of bacteraemia in only 3/10 patients after 12 weeks of a four-drug regimen including oral ciprofloxacin, ethambutol and rifampicin together with parenteral amikacin (7.5 mg/kg/day). In this study, the commonest reason for early drug withdrawal was gastrointestinal intolerance. Two of our patients clearly required longer treatment to achieve blood culture negativity; this could have been caused by a higher mycobacterial blood load in these patients. One limitation of our study is that we did not perform quantitative blood cultures to determine mycobacterial load.
Adverse drug effects were mild and disappeared with drug discontinuation. Survival was comparable to that for other treatments, 1,3 although 80% of our patients presented with AIDS disease. When we looked for late relapse of disseminated MAC infection, which is not undertaken in most studies, 1,3 only four patients showed relapse. For prevention of relapse with clarithromycin-resistant isolates, preliminary studies have shown that a macrolide plus ethambutol is an effective combination. 7
Our regimen is not much more expensive than the standard treatment. In December 1996 in France, the cost of parenteral therapy followed by a two-drug regimen for 1 year, including a nurse at home, was estimated to be FF 33,000, as compared with FF 28,500 for the treatment proposed by Shafran et al. 1 (with the lower dose of rifabutin).
Drugs used to treat mycobacterial diseases in patients with AIDS are associated with frequent side effects, and changes to therapeutic regimens are often required. Our 15 enrolled patients accounted for nearly 15% of all patients with a new diagnosis of disseminated MAC infection during the period of clinical follow-up attending our department. For most of these patients, our therapeutic regimen appeared to be safe and effective.
In conclusion, our therapeutic regimen is useful with current antiretroviral therapies. It improves quality of life for HIV-infected patients with gastrointestinal disorders and seems to improve antibacterial efficacy. Use of clinical parameters as well as bacteriological determination of mycobacterial blood load for a better determination of bacterial efficacy are needed to define precisely the role of this therapeutic approach.
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Notes |
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References |
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2
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Heifets, L. (1996). Susceptibility testing of
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3 . Chiu, J., Nussbaum, J., Bozette, S., Tilles, J. G., Young, L. S., Leedom, J. et al. (1990). Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin and ciprofloxacin. Annals of Internal Medicine 113 , 35861.[ISI][Medline]
4 . Gordon, S. M., Horsburgh, C. R., Peloquin, C. A., Havlik, J. A., Metchock, B., Heifets, L. et al. (1993). Low serum levels of oral antimycobacterial agents in patients with disseminated Mycobacterium avium complex disease. Journal of Infectious Diseases 168, 1559 62.[ISI][Medline]
5 . Jacobson, M. A. & French, M. (1998). Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy. AIDS 12, Suppl. A, S15763.[Medline]
6 . De Lalla, F., Maserati, R., Scarpellini, P., Marone, P., Nicolin, R., Caccamo F. et al. (1992). Clarithromycin-ciprofloxacin-amikacin for therapy of Mycobacterium avium-Mycobacterium intracellulare bacteremia in patients with AIDS. Antimicrobial Agents and Chemotherapy 36, 1567 9.[Abstract]
7 . Bermudez, L. E., Nash, K. A., Petrofsky, M., Young, L. S. & Inderlied, C. B. (1996). Effect of ethambutol on emergence of clarithromycin-resistant Mycobacterium avium complex in the beige mouse model. Journal of Infectious Diseases 174, 121822.[ISI][Medline]
Received 19 May 1998; returned 16 September 1998; revised 26 October 1998; accepted 30 January 1999