Minimal Inhibitory Concentration of Clofazimine Among Clinical Isolates of Nontuberculous Mycobacteria and Its Impact on Treatment Outcome

Background Clofazimine has been regarded as a promising agent for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD). However, its overall effectiveness in vitro and in the clinic remains unknown. Research Question What is the minimal inhibitory concentration (MIC) of clofazimine in clinical isolates and the association between MICs and treatment outcome? Study Design and Methods MICs for clofazimine were measured in clinical isolates from NTM-PD patients who participated in a prospective study at Seoul National University Hospital. The MIC was determined by using the broth microdilution concentration method. Correlation between MIC and conversion to negative of sputum culture with clofazimine was determined. Results Of a total 189 isolates, 133 strains were Mycobacterium avium complex (MAC) and 40 strains were M abscessus. Although the clofazimine MICs for MAC ranged from 0.031 mg/L to 8 mg/L, the values obtained for M abscessus ranged from 0.031 mg/L to 16 mg/L. Of 20 patients who were treated with a regimen including clofazimine, eight achieved negative conversion of sputum culture. All patients with isolates exhibiting clofazimine MIC values ≤ 0.25 mg/L achieved culture conversion. The likelihood of culture conversion in patients with MIC value ≤ 0.25 mg/L was much higher than that of patients with MIC value > 0.5 mg/L (OR, 39.3; P = .021). Interpretation The MICs of clofazimine varied widely in clinical isolates from patients with NTM-PD. Negative conversion of sputum culture with clofazimine use was associated with a lower MIC value. Clofazimine use could be considered in patients with NTM-PD when the MIC value is ≤ 0.25 mg/L. Trial REGISTRY ClinicalTrials.gov; No.: NCT01616745; URL: www.clinicaltrials.gov. Clofazimine has been regarded as a promising agent for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD). However, its overall effectiveness in vitro and in the clinic remains unknown. What is the minimal inhibitory concentration (MIC) of clofazimine in clinical isolates and the association between MICs and treatment outcome? MICs for clofazimine were measured in clinical isolates from NTM-PD patients who participated in a prospective study at Seoul National University Hospital. The MIC was determined by using the broth microdilution concentration method. Correlation between MIC and conversion to negative of sputum culture with clofazimine was determined. Of a total 189 isolates, 133 strains were Mycobacterium avium complex (MAC) and 40 strains were M abscessus. Although the clofazimine MICs for MAC ranged from 0.031 mg/L to 8 mg/L, the values obtained for M abscessus ranged from 0.031 mg/L to 16 mg/L. Of 20 patients who were treated with a regimen including clofazimine, eight achieved negative conversion of sputum culture. All patients with isolates exhibiting clofazimine MIC values ≤ 0.25 mg/L achieved culture conversion. The likelihood of culture conversion in patients with MIC value ≤ 0.25 mg/L was much higher than that of patients with MIC value > 0.5 mg/L (OR, 39.3; P = .021). The MICs of clofazimine varied widely in clinical isolates from patients with NTM-PD. Negative conversion of sputum culture with clofazimine use was associated with a lower MIC value. Clofazimine use could be considered in patients with NTM-PD when the MIC value is ≤ 0.25 mg/L. ClinicalTrials.gov; No.: NCT01616745; URL: www.clinicaltrials.gov. ResponseCHESTVol. 160Issue 1PreviewWe appreciate the comments from Drs Aksamit and Marras on our article, which reported the correlation between the minimal inhibitory concentration (MIC) of clofazimine and its clinical impact among patients with Mycobacterium avium complex and M abscessus pulmonary disease.1 The authors raised several crucial issues. Full-Text PDF Clofazimine Drug Susceptibility Testing for Nontuberculous Mycobacteria: A Call to ArmsCHESTVol. 160Issue 1PreviewWe read with interest the study in CHEST (February 2021) by Kwak et al1 regarding the association between clofazimine minimal inhibitory concentration (MIC) and treatment outcomes for Mycobacterium avium complex (MAC) and M abscessus. Full-Text PDF