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Clarithromycin against Mycobacterium avium complex infections
1Department of Microbiology, University of Colorado Health Sciences Center, USA.
Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
|February 1, 1996
Summary
New macrolides like clarithromycin are effective against Mycobacterium avium infections. However, pre-existing resistant mutants can cause treatment relapse, highlighting the need for combination therapies to prevent clarithromycin resistance.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Mycobacterium avium infections pose a significant therapeutic challenge.
- The advent of macrolides, clarithromycin and azithromycin, marked a turning point in treatment.
- Controlled clinical trials were essential for evaluating these new agents.
Purpose of the Study:
- To assess the efficacy of clarithromycin and azithromycin in treating Mycobacterium avium infections.
- To investigate the mechanisms of clarithromycin resistance in M. avium.
- To evaluate methods for determining clarithromycin susceptibility in M. avium isolates.
Main Methods:
- Controlled clinical trials were conducted in acquired immune deficiency syndrome (AIDS) and non-AIDS patients.
- Minimum inhibitory concentration (MIC) determination using agar and broth methods were employed.
- Susceptibility testing breakpoints were established for both methods.
Main Results:
- Clarithromycin demonstrated high efficiency, eliminating bacteremia in most disseminated infection cases.
- Relapses of bacteremia were attributed to pre-existing clarithromycin-resistant mutants (10^-8 or 10^-9).
- Clarithromycin resistance was linked to a mutation in the 23S rRNA gene, with cross-resistance observed with azithromycin.
Conclusions:
- Clarithromycin and azithromycin represent significant advancements in treating M. avium infections.
- The emergence of resistant mutants is a critical issue necessitating combination therapy.
- Ongoing clinical trials aim to identify effective companion drugs to prevent macrolide resistance.