The turning point in antimicrobial therapy of Mycobacterium avium infections 
came with the development of two new macrolides, clarithromycin and 
azithromycin. Controlled clinical trials, the first ever conducted with any 
agent among patients with M. avium infection, indicated the high efficiency of 
clarithromycin, in either acquired immune deficiency syndrome (AIDS) patients 
having a disseminated infection or non-AIDS patients with localized pulmonary 
disease. Monotherapy with clarithromycin resulted in elimination of bacteremia 
in almost all patients with disseminated infection, which is inevitably followed 
by a relapse of bacteremia in patients who survived long enough to reach this 
event. The strains susceptible to clarithromycin isolated before therapy 
contained 10(-8) or 10(-9) resistant mutants, and the relapses of bacteremia 
were caused by multiplication of these pre-existing mutants. 
Clarithromycin-resistance was associated with a mutation in the 23S rRNA gene. 
Cross-resistance between clarithromycin and azithromycin was confirmed with 
laboratory mutants and clinical isolates. At least two methods for determining 
the susceptibility of the M. avium isolates to clarithromycin are available: one 
is minimum inhibitory concentration (MIC) determination on Mueller-Hinton agar 
(pH 7.4) supplemented with 10% Oleic acid-albumin-dextrose catalase, the other 
is MIC determination in 7H12 broth, also at pH 7.4. The breakpoints for 
'susceptible' for these methods are < or = 8.0 micrograms/ml and < or = 2.0 
micrograms/ml, respectively. The breakpoints for 'resistant' are > 128 
micrograms/ml for the agar method and > 32.0 micrograms/ml for the broth method. 
The predictability value of MIC determination was confirmed by comparing the 
test results with the patients' clinical and bacteriological response to 
therapy. The remaining major problem in the therapy of the M. avium infections 
is a selection of companion drugs to be used in combination with clarithromycin 
(or azithromycin) to prevent the emergence of the macrolide-resistance. A number 
of clinical trials are now in progress to find a solution to this problem.