Clarithromycin Resistance in Mycobacterium abscessus

We read with interest the article by Sanguinetti et al. titled “Fatal Pulmonary Infection Due to Multidrug-Resistant Mycobacterium abscessus in a Patient with Cystic Fibrosis,” which appeared in the February 2001 issue (5). We would like to point out some additional information relating to the authors' comment, “to our knowledge, this is the first evidence of true resistance to clarithromycin, which is considered the most active drug against M. chelonae.” First, the case report involves Mycobacterium abscessus, not M. chelonae. The two names are not synonymous and should not be used interchangeably (10). The organisms have different biologies, are readily differentiated in the laboratory, and have different drug susceptibilities (2, 3, 6, 8). (Essentially all cases of chronic lung disease caused by rapidly growing mycobacteria in the setting of cystic fibrosis are due to M. abscessus [3].)

Second, there have been several previous reports of acquired clarithromycin resistance in isolates of M. abscessus and the closely related M. chelonae, and the genetics of this resistance have been well characterized (7, 9, 11). We would especially call the authors' attention to an article describing the study of clarithromycin resistance in a series of 800 isolates of M. chelonae and M. abscessus. Eighteen of 800 clinical isolates (2.3%) submitted for susceptibility testing between 1990 and 1995 were found to be resistant to clarithromycin; 10 of these isolates were M. abscessus (9). The underlying conditions most commonly associated with the development of macrolide resistance in M. abscessus following clarithromycin therapy were cystic fibrosis (as in the case reported by the authors) and disseminated cutaneous disease. Sequencing studies of the 23S rRNA gene revealed that 94% of the clarithromycin-resistant isolates had a mutation involving the adenine at position 2058 or 2059 (Escherichia coli numbering system). Selected laboratory mutants resistant to clarithromycin had the same mutations, as have other species of mycobacteria and bacteria with acquired clarithromycin resistance (1, 4). The study also revealed that M. chelonae and M. abscessus have only a single copy of the ribosomal operon in their genome and hence demonstrate susceptibility to a single point mutation resulting in high-level (clinical) resistance.