Article Figures & Data
Figures
- FIG 1
Decision algorithm for predicting drug resistance in M. abscessus based on the literature search, with the numbers of isolates meeting each predictive criterion shown. Numbers in parentheses represent the number resistant/the number sensitive. *, 4 isolates had intermediate susceptibility; pos, position.
- FIG 2
Flow diagram showing the stages of the systematic literature search.
Tables
- TABLE 1
Resistance-determining mutations for clarithromycin identified in the literature searcha
erm(41) length Nucleotide at: Phenotype [reference(s)] erm(41) position 28 rrl position 2270 (2058) rrl position 2271 (2059) Other Full T A A Inducible resistance (3, 15, 16, 20, 21, 27–37), sensitive (33) Truncated A A Sensitive (9, 15, 20, 21, 29, 32–38) Full C A A Sensitive (15, 16, 20, 21, 28–33, 35–37, 39) Full or truncated C or T G A Resistant (3, 15, 16, 18, 20, 21, 27, 28, 36–41) Full or truncated C or T C A Resistant (3, 15, 20, 21, 28, 38, 41) Full or truncated T T A Resistant (15, 20, 27) Full A C Resistant (20, 27, 40, 41) Full or truncated T or C A G Resistant (15, 16, 18, 20, 21, 28, 37, 40) Truncated A T Resistant (27) Full T A A C19T in erm(41) Sensitive (42) Truncated A A A2269G in rrl (2057) Resistant (16) Full Unknown Unknown Unknown A2293C in rrl (2082) + G2281C in rrl (2069) Resistant (41) ↵a M. abscessus numbering is used, with E. coli numbering provided in parentheses.
- TABLE 2
WGS predictions versus DST phenotype for clarithromycina
Genomic prediction No. of isolates with the following in vitro phenotype: Sensitive Resistant Intermediate No prediction 2 18 0 Inducible resistance 27 74 0 Resistant 0 21 0 Sensitive 52 5 4 ↵a The sensitivity (95%; 95% CI, 89 to 98%), specificity (66%; 95% CI, 54 to 76%), positive predictive value (78%; 95% CI, 69 to 85%), and negative predictive value (91%; 95% CI, 81.0 to 97%) were calculated by excluding isolates with an intermediate phenotype and those for which no prediction was made due to inadequate coverage at key positions.
- TABLE 3
Summary of genotypes and corresponding clarithromycin phenotypes for the 203 isolatesa
Organism Nucleotide at erm(41) pos. 28 erm(41) length Nucleotide at erm(41) pos. 19 Nucleotide at rrl pos.: N Phenotypeb Prediction 2269 2270 2271 M. abscessus subsp. abscessus T Full C A C A 5 5R R T Full C A T A 2 2R R C Full C A A A 37 4I, 2R, 31S S T Full C A A A 87 62R, 25S R 12 10R, 2Sc M. abscessus subsp. bolletii T Full C G A A 1 1R R T Full C A G A 2 2R R T Full C A A A 13 11R, 2S R 4 4Rc M. abscessus subsp. massiliense T Truncated C A C A 3 3R R T Truncated C A G A 3 3R R T Truncated C A A G 5 5R R T Truncated C A A A 24 21S, 3R S T Full C A A A 1 1R R 4 4Rc ↵a pos., M. abscessus numbering position in the indicated gene; prediction, genotypic prediction using the algorithm shown in Fig. 1; N, total number of isolates with the genotype.
↵b The phenotype indicates the number of isolates that are sensitive (S), resistant (R), or inducibly resistant (I).
↵c These isolates were excluded due to inadequate coverage over rrl positions 2270 and 2271.
- TABLE 4
Mutations (both novel and previously described) detected during the de novo search for resistance-determining SNPsc
Position Nucleotide/amino acid change Rule metd rrl 2039 A > G 1 rrl 1401 T > C 2 rrl 371 T > C 2 rrl 795 G > A 1 rrl 2270a A > C 1 rrl 2270a A > G 2 rrl 2271a A > G 2 rrl 2270a A > T 2 erm(41) 131 A > V 2 rrl 2279 G > A 2 rrl 2269a A > G 2 erm(41) −31b A > T 2 rrl 1932 A > G 2 ↵a The mutation is already described in the literature. M. abscessus rrl numbering 2270 and 2271 is E. coli numbering 2058 and 2059, respectively.
↵b Mutation in the erm(41) promoter region 31 bases upstream of start of the coding region.
↵c All numbering is relative to that for M. abscessus.
↵d Rule 1, occurs as the only SNP in relevant regions in resistant isolates; rule 2, all samples are resistant when SNP occurs, and the SNP is never seen in sensitive isolates.
