Abstract
Mutations in the erm(41) gene of M.abscessus group organisms are associated with differences in inducible macrolide resistance, with current recommendations being to hold rapidly growing isolates for up to 14 days in order to ensure that resistance which develops more slowly can be detected. This study aimed to determine the ideal incubation time for accurate identification of inducible macrolide resistance as well as to determine if there was an association between the time taken to detect inducible resistance in M.abscessus group organisms and their erm(41) sequevar. We amplified and sequenced the erm(41) genes of a total of 104 M.abscessus group isolates and determined their sequevars. The isolates were tested for phenotypic clarithromycin resistance at days 7, 10, 14 and 21, using Trek Diagnostics Sensititre RAPMYCO microbroth dilution plates. Associations between erm(41) gene sequevars and time to detection of resistance were evaluated using Fisher’s exact test in R. The samples included in this study fell into 14 sequevars, with the majority of samples falling into Sequevar02 (16), Sequevar06 (15), Sequevar08 (7) and Sequvar 15 (31), and several isolates that were in small clusters, or unique. The majority (82.7%) of samples exhibiting inducible macrolide resistance were interpreted as resistant by day 7. Two isolates in Sequevar02, which has a T28C mutation that is associated with sensitivity, showed intermediate resistance at day 14, though the majority (13) were sensitive at day 14. The majority of isolates with inducible macrolide resistance fell into Sequevars 06,08 and 15, none of which contain the T28C mutation. These sequevars were analyzed to determine if there was any correlation between sequevar and time to detection of resistance. None was found. Based on these findings, we recommend the addition of a day 7 read to the CLSI guidelines to improve turn-around-times for these isolates. It is also recommended that erm(41) gene sequencing be added to routine phenotypic testing for the resolution of cases with difficult-to-interpret phenotypic results.
Highlights
Mycobacterium abscessus is implicated in many clinically important infections including respiratory infections and skin infections
Twenty one M. chelonae strains, which lack the mechanism for inducible macrolide resistance (Nash, 2009), were inoculated into panels and incubated for 21 days to evaluate the stability of the clarithromycin in the panel at that extended time point
Within Sequevar02, 2 M. abscessus subsp. abscessus isolates with T28C mutations intermediate interpretations at day 14 and 1 strain closely related to M. abscessus (1 bp away by 16s rRNA gene sequencing) had an intermediate interpretation at day 21
Summary
Mycobacterium abscessus is implicated in many clinically important infections including respiratory infections and skin infections. More recently the combination of these two subspecies is being re-evaluated, with one of the major items of contention being inducible macrolide resistance and potential treatment differences between the three previously proposed subspecies [3,4,5,6]. The erythromycin ribosomal methlylase (erm) gene, which is associated with inducible resistance to macrolide antibiotics, has been identified in several clinically relevant rapidly growing mycobacteria (RGM), including the erm(41) gene in the M. abscessus group [7,8,9]. Detection of inducible macrolide resistance can be expedited by sequencing the erm(41) gene that is present in organisms. This study aimed to determine the ideal incubation time for the detection of inducible macrolide resistance and establish whether there is a correlation between the length of time it takes to detect inducible macrolide resistance in M.abscessus group organisms and their erm(41) sequevars
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