Genetic correlates of clarithromycin susceptibility among isolates of the Mycobacterium abscessus group and the potential clinical applicability of a PCR-based analysis of erm(41)

Author(s)

de Carvalho, Natalia F. G. ^[1] ; Pavan, Fernando ^[2] ; Sato, Daisy N. ^[2] ; Leite, Clarice Q. F. ^[2] ; Arbeit, Robert D. ^[3] ; Chimara, Erica ^[1]

Affiliation

^[1] Adolfo Lutz Inst, Bacteriol Ctr, TB & Mycobacteriosis Lab, Sao Paulo - Brazil

^[2] UNESP, Fac Ciencias Farmaceut, Araraquara - Brazil

^[3] Tufts Med Ctr, Div Infect Dis, Boston, MA - USA

• Document type: Journal article
• Source: Journal of Antimicrobial Chemotherapy; v. 73, n. 4, p. 862-866, APR 2018.
• Web of Science Citations: 5

Abstract

Objectives: To define the genetic basis of clarithromycin resistance among isolates of the Mycobacterium abscessus group (MAG). Methods: We analysed 133 isolates identified as MAG. Species identification was confirmed by sequencing the rpoB gene. Clarithromycin susceptibility testing was performed according to CLSI recommendations, with an extended 14 day incubation. Known resistance genotypes of erm(41) and rrl were identified by sequencing; the presence of deletions in erm(41) was detected by PCR. Results: The 133 MAG isolates included 82 M. abscessus, 27 Mycobacterium massiliense and 24 Mycobacterium bolletii. After the 3 day incubation, only five isolates demonstrated clarithromycin resistance (R); after 14 days of extended incubation, an additional 92 exhibited inducible resistance (IR), with the remaining being susceptible (S). The distribution of susceptibility phenotypes varied among the species. Among M. abscessus isolates, 11% were S, 84% IR and 5% R; among M. bolletii isolates, 96% were IR and 4% R; and among M. massiliense isolates 100% were S. Sequencing of rrl identified only a single isolate with the A205 8G mutation. Deletions in erm(41) were present in 30 susceptible isolates; among the remaining 103 isolates, 97 were R or IR (sensitivity, 83%; specificity, 100%; positive predictive value, 100%; negative predictive value, 94%). Among the six susceptible isolates without deletions, all carried the erm(41) T28C pointmutation. Conclusions: A significant proportion of MAG isolates demonstrate inducible resistance to clarithromycin that is only detectable with an extended 14 day incubation. Further, the majority of clarithromycin-susceptible MAG isolates have characteristic deletions in erm(41) that can rapidly and reliably be detected by a simple PCR. (AU)

• FAPESP's process: 14/50094-4 - Use of MGIT 960 TB eXiST system as susceptibility test for Mycobacterium abscessus: standardization and evaluation
• Grantee: Erica Chimara Silva
• Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)