Clarithromycin-resistant Mycobacterium avium is still susceptible to treatment with clarithromycin and is virulent in mice

Resistance to clarithromycin in breakthrough Mycobacterium avium complex (M AC) isolates typically occurs 3 to 4 months after the initiation of monothe rapy in bacteremic AIDS patients, It has been suggested that continuation o f clarithromycin therapy still results in clinical and microbiological impr ovement. To study this paradox, C57BL/6 beige mice were infected with a cla rithromycin-resistant (MIC, greater than or equal to 128 mu g/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg o f body weight/day alone or in combination with ethambutol (100 mg/kg/day) f or 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 1 01 had bacterial loads reduced by 90% in the liver and 91% in the spleen (P < 0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (P = 0.009) and a 71% reduction in the spleen (P = 0.009), compared with the results f or the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within inf ected tissues.