The Clarithromycin Susceptibility Genotype Affects the Treatment Outcome of Patients with Mycobacterium abscessus Lung Disease.

Qi Guo,Bing Li,Zhemin Zhang,Shiyi Yang,Wei Ma,Fangyou Yu,Meiping Ye,Haiqing Chu

doi:10.1128/aac.02360-17

Abstract

ABSTRACTMycobacterium abscessus accounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria. The association between clarithromycin sensitivity and treatment outcome is clear. However, M. abscessus culture and antibiotic susceptibility testing are time-consuming. Clarithromycin susceptibility genotyping offers an alternate, rapid approach to predicting the efficacy of clarithromycin-based antibiotic therapy. M. abscessus lung disease patients were divided into two groups based upon the clarithromycin susceptibility genotype of the organism isolated. A retrospective analysis was conducted to compare the clinical features, microbiological characteristics, and treatment outcomes of the two groups. Several other potential predictors of the response to treatment were also assessed. Sixty-nine patients were enrolled in the clarithromycin-resistant genotype group, which included 5 infected with rrl 2058-2059 mutants and 64 infected with erm(41)T28-type M. abscessus; 31 were in the clarithromycin-sensitive group, i.e., 6 and 25 patients infected with genotypes erm(41)C28 and erm(41) M type, respectively. The results showed that lung disease patients infected with clarithromycin-sensitive and -resistant M. abscessus genotypes differed significantly in clarithromycin-based combination treatment outcomes. Patients infected with the clarithromycin-sensitive genotype exhibited higher initial and final sputum-negative conversion and radiological improvement rates and better therapeutic outcomes. Multivariate analysis demonstrated that genotyping was a reliable and, more importantly, rapid means of predicting the efficacy of clarithromycin-based antibiotic treatment for M. abscessus lung disease.

Highlights

Mycobacterium abscessus accounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria
One hundred M. abscessus lung disease patients who conformed to our recruitment criteria were enrolled and divided into CLA-resistant and -sensitive genotype groups according to the rrl and erm(41) sequevar
A significantly greater incidence of cavity-like manifestations occurred in computed tomography (CT) scans of patients infected with isolates with the CLA-resistant genotype than in patients infected with isolates with the CLA-sensitive genotype (50/69 versus 8/31; P Ͻ 0.001)

Summary

Introduction

Mycobacterium abscessus accounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria. M. abscessus lung disease patients were divided into two groups based upon the clarithromycin susceptibility genotype of the organism isolated. The results showed that lung disease patients infected with clarithromycin-sensitive and -resistant M. abscessus genotypes differed significantly in clarithromycin-based combination treatment outcomes. Multivariate analysis demonstrated that genotyping was a reliable and, more importantly, rapid means of predicting the efficacy of clarithromycin-based antibiotic treatment for M. abscessus lung disease. M. abscessus accounts for 65 to 80% of the cases of lung disease caused by rapidly growing mycobacteria and has emerged as an important pathogen for patients with bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis (6–11). Mycin (CLA) exhibits convincing evidence of clinical efficacy for treatment of M. abscessus lung disease (8). Deletion of erm(41) nucleotides 64 and 65, or deletion of nucleotides 159 to 432, results in the loss of erm(41) gene function (M type) and a gain in CLA sensitivity (14, 16)

Methods

Results

Conclusion