Article Summaries

PI-TB Article Summaries


Is a Clofazimine-containing regimen effective for the treatment of Mycobacterium abscessus lung disease?


Bumhee Yang, Byung Woo Jhun, Seong Mi Moon, Hyun Lee, Hye Yun Park, Kyeongman Jeon, Dae Hun Kim, Su-Young Kim, Sung Jae Shin, Charles L. Daley, Won-Jung Koha. A Clofazimine-containing regimen for the treatment of Mycobacterium abscessus Lung Disease. Antimicrob Agents Chemother 24; (61)6. 2017


Mycobacterium abscessus subspecies abscessus (Mab) is a rapidly growing mycobacteria (RGM) well known as the most difficult to treat mycobacterial lung disease in patients with CF and non-CF bronchiectasis.  As per ATS/IDSA guidelines, macrolide-based antibiotic therapy combined with intravenous amikacin (AMK) with either cefoxitin or imipenem has poor outcomes. Clofazimine (CFZ) which is mainly used in the treatment of leprosy has been recently introduced for the treatment of multidrug-resistant or extensively drug-resistant tuberculosis and had shown clinical efficacy in treating M avium complex lung disease. Although both US and European Cystic Fibrosis Foundation recently recommended that the continuation phase of Mab lung disease treatment should include CFZ, current published evidence lacks data on clinical efficacy of CFZ on Mab lung disease.

In this study, the authors retrospectively reviewed the clinical, radiologic, and microbiologic responses of 42 patients treated with CFZ-containing regimens and found that these regimens were moderately effective. Of these 42 patients, 15 (36%) were commenced on a CFZ-containing regimen at the beginning of treatment, while 27 (64%) had CFZ added to their treatment regimen following failure of sputum culture conversion after a median 113.6 weeks of therapy. Among these 2 groups, Mab isolates demonstrated similar initial rates of inducible resistance to clarithromycin (CLR) at 87% and 85% respectively.

All patients in the initial treatment group received initial 4-week intravenous combination antibiotic therapy. 13 patients in the salvage treatment group received 4-week intravenous combination antibiotic therapy after rehospitalisation, while 14 received CFZ in addition to their continuing oral regimen. Surgical intervention was performed on 3 patients.

Treatment response after 12 months of a CFZ-containing regimen was assessed. There was an overall 81% treatment response rate based on symptoms and a 31% response rate based on radiographic findings. This rate may be suboptimal as CXR was used to document progression of Mab lung disease in 9 patients. Sputum culture conversion was achieved in 40% (6/15) of patients in the initial treatment group which is higher than previously reported rates of 25% to 34% after 12 months of antibiotic treatment without CFZ. The culture conversion rate was only 15% in the salvage treatment group, and this did not differ between those started on CFZ with intravenous combination antibiotic therapy and those started on CFZ in addition to ongoing oral regimens. 23 (55%) patients experienced adverse effects from CFZ, primarily GI upset and skin discoloration, resulting either in its discontinuation (18 patients) or in a dose reduction (5 patients). In conclusion, this study demonstrates moderate efficacy of CFZ-containing regimens in the treatment of Mab lung disease. However, small sample size, retrospective nature of the study, treatment heterogeneity within groups and lack of a CFZ-free control group warrant a prospective evaluation of CFZ in Mab lung disease.