Relationship Between Clarithromycin MICs and Treatment Responses in Mycobacterium avium Complex Pulmonary Disease

Abstract

Background Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear.Methods We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into 4 groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the likelihood of microbiological cure. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis.Results Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs <= 0.5, 1-2, 4-8, and >= 32 mu g/mL, respectively (P = .181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (<= 8 mu g/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs >= 32 mu g/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval [CI]: 0.06-1.07; P = .06).Conclusions Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range but were likely to be worse for patients with strains having MICs >= 32 mu g/mL. We analyzed 436 patients with Mycobacterium avium complex pulmonary disease and found a similar likelihood of microbiological cure for strains with clarithromycin minimum inhibitory concentrations (MICs) <= 8 mu g/mL, while strains with MICs >= 32 mu g/mL showed a trend toward worse outcomes.