Correction to: Eur J Med Res (2019) 24:38 10.1186/s40001-019-0397-2
The original publication of this article [1] contained few erroneous paragraphs and errors in Table 1 and Table 2. The first four paragraphs are in the ‘Results’ section while the last four paragraphs are in the ‘Discussion’ section. The errors in Table 1 involve the number of isolates tested for pyrazinamide and pyrazinamide susceptible isolates, ethambutol-susceptible isolates with a mutation and number of resistant isolates with a mutation for streptomycin. The error in Table 2 involves wrong codon number for a mutation in isolate KM17-01 in Cluster XII for gidB gene. The updated informations have been indicated in bold and also refer corrected Tables 1 and 2.
Table 1.
Phenotypic resistance by MGIT 960 system to anti-TB drugs among 93 multidrug-resistant M. tuberculosis isolates and number of susceptible and resistant isolates with mutations in target genes for each drug
| Anti-tuberculosis drug | No. of isolates tested | No. of susceptible isolates | No. of susceptible isolates with mutationa | No. of resistant isolates | No. (%) of resistant isolates with mutationa |
|---|---|---|---|---|---|
| Rifampicin | 93 | 0 | 0 | 93 | 93 (100) |
| Isoniazid | 93 | 0 | 0 | 93 | 92 (98.9) |
| Pyrazinamide | 46 | 10 | 0 | 36 | 30 (83.3) |
| Ethambutol | 93 | 52 | 39b | 41 | 38 (92.7) |
| Streptomycin | 93 | 34 | 0 | 59 | 51 (86.4) |
aResistance conferring mutations were detected in rpoB for rifampicin, katG + inhA for isoniazid, pncA for pyrazinamide, embB for ethambutol, and rpsL + rrs for streptomycin
bM. tuberculosis isolates with embB mutations usually confer low level of resistance to ethambutol which are often missed by the MGIT 960 system [23, 28]
Table 2.
Detailed clinical, demographic and molecular characteristics of 42 M. tuberculosis isolates in 16 (Cluster I to Cluster XVI) clusters
| Cluster no. | Clinica specimen | Isolate no. | Year of isolation | Patient’s nationality | Spoligotyping data | Genetic alteration detected in | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SIT | Mtb family | rpoB | katG | inhA | pncA | embB | rpsL | rrs | gidB | rpsA | |||||
| I | Sputum | KM06-153 | 2006 | Indian | 255 | Beijing | TCG456TTG | ACG315ACC | WT | WT | ATG306GTG | AAG43AGG | WT | N. D. | N. D. |
| CSF | KM09-22 | 2009 | Indian | 255 | Beijing | TCG456TTG | ACG315ACC | WT | WT | ATG306GTG | AAG43AGG | WT | N. D. | N. D. | |
| Sputum | KM13-37 | 2013 | Indian | 1 | Beijing | TCG456TTG | ACG315ACC | WT | WT | ATG306GTG | AAG43AGG | WT | N. D. | N. D. | |
| FNA | KM16-06 | 2016 | Nepalese | 1 | Beijing | TCG456TTG | ACG315ACC | WT | WT | ATG306GTG | AAG43AGG | WT | N. D. | N. D. | |
| FNA | KM17-03 | 2017 | Indian | 1 | Beijing | TCG456TTG | ACG315ACC | WT | WT | ATG306GTG | AAG43AGG | WT | N. D. | N. D. | |
| II | Sputum | KM14-58 | 2014 | Nepalese | 1 | Beijing | TCG456TTG | ACG315ACC | WT | GTG139GCG | ATG306GTG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC |
| Sputum | KM14-69 | 2014 | Indian | 1 | Beijing | TCG456TTG | ACG315ACC | WT | GTG139GCG | ATG306GTG | AAG43AGG | WT | GCA205GCG | WT | |
| III | Sputum | KM08-501 | 2008 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | GGT139GTT | ATG306GTG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC |
| Sputum | KM08-502 | 2008 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | GGT139GTT | ATG306GTG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| Sputum | KM09-207 | 2009 | Indian | 1 | Beijing | TCG456TTG | ACG315ACC | WT | GGT139GTT | ATG306GTG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| IV | Sputum | KM12-05 | 2012 | Ethiopian | 21 | CAS1-Kili | TCG456TTG | ACG315ACC | WT | Ins193A (FS) + TCC65TCT | ATG306GTG | AAG88AGG | WT | N. D. | N. D. |
| Sputum | KM12-17 | 2012 | Ethiopian | 1144 | T1 | TCG456TTG | ACG315ACC | WT | Ins193A (FS) + TCC65TCT | ATG306GTG | AAG88AGG | WT | N. D. | N. D. | |
| Sputum | KM15-08 | 2015 | Ethiopian | 21 | CAS1-Kili | TCG456TTG | ACG315ACC | WT | Ins193A (FS) + TCC65TCT | ATG306GTG | AAG88AGG | WT | N. D. | N. D. | |
| V | Sputum | KM07-333 | 2007 | Indonesian | Orphan | N. A. | TCG456TTG | ACG315ACC | WT | WT | WT | WT | WT | N. D. | N. D. |
| Sputum | KM10-23 | 2010 | Indian | 355 | EAI3-IND | TCG456TTG | ACG315ACC | WT | WT | WT | WT | WT | N. D. | N. D. | |
| VI | Sputum | KM07-293 | 2007 | Filipino | 194 | LAM2 | TCG456TTG | ACG315ACC | WT | WT | CAG497CGG | WT | WT | N. D. | N. D. |
| Sputum | KM12-01 | 2012 | Filipino | 25 | CAS1-Delhi | TCG456TTG | ACG315ACC | WT | WT | CAG497CGG | WT | WT | N. D. | N. D. | |
| VII | Sputum | KM09-202 | 2009 | Ethiopian | 47 | H1 | GTC176TTC | ACG315ACC | WT | WT | WT | WT | WT | N. D. | N. D. |
| Sputum | KM15-17 | 2015 | Indian | 47 | H1 | GTC176TTC | ACG315ACC | WT | WT | WT | WT | WT | N. D. | N. D. | |
| VIII | Sputum | KM14-67 | 2014 | Ethiopian | 149 | T3-ETH | TCG456TTG | ACG315ACC | WT | − 11 A/G | ATG306ATC | WT | WT | GGT69GAT | WT |
| Sputum | KM15-21 | 2015 | Ethiopian | 149 | T3-ETH | TCG456TTG | ACG315ACC | WT | − 11 A/G | ATG306ATC | WT | WT | GGT69GAT | WT | |
| IX | Sputum | KM07-283 | 2007 | Indian | 26 | CAS1-Delhi | TCG456TTG | ACG315ACC | WT | TCC65TCT | ATG306ATA | WT | WT | N. D. | N. D. |
| Sputum | KM14-68 | 2014 | Indian | Orphan | N. A. | TCG456TTG | ACG315ACC | WT | TCC65TCT | ATG306ATA | WT | WT | N. D. | N. D. | |
| Sputum | KM17-20 | 2017 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | CAG497CGG | AAG43AGG | WT | GAA92GAC + GCA205GCG | WT | |
| X | Sputum | KM17-22 | 2017 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | CAG497CGG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC |
| Sputum | KM17-73 | 2017 | Indian | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | CAG497CGG | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| Pus | KM11-503 | 2011 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| Sputum | KM14-56 | 2014 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| XI | Sputum | KM15-13 | 2015 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC |
| Sputum | KM15-26 | 2015 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| Sputum | KM17-02 | 2015 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| Sputum | KM17-69 | 2017 | Kuwaiti | 1 | Beijing | TCG456TTG | ACG315ACC | WT | − 11 A/G | GGC406GAC | AAG43AGG | WT | GAA92GAC + GCA205GCG | CGA212CGC | |
| XII | Sputum | KM16-32 | 2016 | Egyptian | 19 | EAI2-Manila | CAC451TAC | ACG315ACC | − 15 C/T | GAA37AAA | CTG355CTA + GAG378GCG | WT | WT | GTG110GTT + GCA205GCG | WT |
| Sputum | KM17-01 | 2017 | Filipino | 19 | EAI2-Manila | CAC451TAC | ACG315ACC | − 15 C/T | GAA37AAA | CTG355CTA + GAG378GCG | WT | WT | CTC59TTC + GTG110GTT + GCA205GCG | WT | |
| XIII | Pus | KM07-297 | 2007 | Indian | Orphan | N. A. | CAC451GAC | WT | − 15 C/T | TCC65TCG + Ins 453T (FS) | ATG306CTG | WT | WT | N. D. | N. D. |
| FNA | KM11-502 | 2015 | Indian | 3361 | T1 | CAC451GAC | WT | − 15 C/T | TCC65TCG + Ins 453T (FS) | ATG306CTG | WT | WT | N. D. | N. D. | |
| XIV | Sputum | KM06-48 | 2006 | Egyptian | 53 | T1 | TCG456TTG | WT | − 15 C/T | WT | WT | WT | WT | N. D. | N. D. |
| Tissue | KM06-277 | 2006 | Filipino | 19 | EAI2-Manila | TCG456TTG | WT | − 15 C/T | WT | WT | WT | WT | N. D. | N. D. | |
| XV | Sputum | KM16-33 | 2016 | Indian | 8 | EAI3/EAI5 | CAC451TAC | ACG315ACC | WT | CTG35CCG | ATG306GTG + GAG378GCG | AAG43AGG | WT | GTG110GTT + GCA205GCG | WT |
| Sputum | KM17-06 | 2017 | Filipino | 8 | EAI3/EAI5 | CAC451TAC | ACG315ACC | WT | CTG35CCG | ATG306GTG + GAG378GCG | AAG43AGG | WT | GTG110GTT + GCA205GCG | WT | |
| XVI | Sputum | KM07-231 | 2007 | Indian | Orphana | CAS1-Delhi | ATG440ATA + GAC441TAC | ACG315ACC | WT | TCC65TCT | GGC406TGC | WT | WT | GCA205GCG + Del 350G (FS) | WT |
| Sputum | KM07-252 | 2007 | Syrian | Orphana | CAS1-Delhi | ATG440ATA + GAC441TAC | ACG315ACC | WT | TCC65TCT | GGC406TGC | WT | WT | GCA205GCG + Del 350G (FS) | WT | |
Clusters containing MDR-TB strains with identical patterns and isolated within a period of nearly 2 years are shown as underlined. Synonymous mutations are italicized
N. A., not applicable; N. D., not done; CSF, cerebrospinal fluid; FNA, fine needle aspirate; SIT, shared international type; Mtb family, M. tuberculosis family; WT, wild-type sequence; Ins, insertion mutation; (FS), frame shift mutation, fine needle aspirate
aBoth isolates displayed identical spoligotyping pattern
Incorrect: Although all 93 MDR-TB isolates were tested for susceptibility to pyrazinamide, only 47 isolates yielded interpretable results; 11 isolates were susceptible and 36 were resistant to this drug including 15 isolates that were resistant to all five drugs. The remaining 46 MDR-TB strains failed to grow at the reduced pH in the absence of the drug.
Correct: Although all 93 MDR-TB isolates were tested for susceptibility to pyrazinamide, only 46 isolates yielded interpretable results; 10 isolates were susceptible and 36 were resistant to this drug including 15 isolates that were resistant to all five drugs. The remaining 47 MDR-TB strains failed to grow at the reduced pH in the absence of the drug.
Incorrect: The proportion of MDR-TB isolates exhibiting resistance conferring mutations in target genes varied for different anti-TB drugs, being highest for rifampicin and lowest for streptomycin (Table 1).
Correct: The proportion of MDR-TB isolates exhibiting resistance conferring mutations in target genes varied for different anti-TB drugs, being highest for rifampicin and lowest for streptomycin among SIRE drugs (Table 1).
Incorrect: PCR-sequencing of pncA identified mutations in 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 46 isolates for which phenotypic DST data for pyrazinamide was not available while all 11 isolates phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.
Correct: PCR-sequencing of pncA identified mutations in 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 47 isolates for which phenotypic DST data for pyrazinamide was not available while all 10 isolates phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.
Incorrect: Fifty isolates contained mutations at embB306 (M306V, n = 28; M306I, n = 19 and M306L, n = 3), 15 isolates contained a mutated embB406 (G406D, n = 8; G406A, n = 4; G406C, n = 2 and G406S, n = 1), 10 isolates contained a mutated embB497 (Q497R, n = 6; Q497K, n = 3 and Q497H, n = 1) and one isolate contained a mutation (Y319S) at embB319.
Correct: Fifty isolates contained mutations at embB306 (M306V, n = 28; M306I, n = 19 and M306L, n = 3), 16 isolates contained a mutated embB406 (G406D, n = 8; G406A, n = 5; G406C, n = 2 and G406S, n = 1), 10 isolates contained a mutated embB497 (Q497R, n = 6; Q497K, n = 3 and Q497H, n = 1) and one isolate contained a mutation (Y319S) at embB319.
Incorrect: Forty-nine of 59 MDR-TB strains additionally resistant to streptomycin contained a mutation in the target genes analysed (Table 1), many of which have been described previously [23, 28]. These included 44 isolates with a mutation in rpsL (K43R, n = 33; K43T, n = 1; K88R, n = 5; K88T, n = 4; K88M, n = 1), four isolates with a mutation in rrs 500 or 900 region (A514C, n = 1; C517T, n = 1; G878A, n = 1 and A906G, n = 1) and one isolate with rpsL K88R + rrs C602A double mutation.
Correct: Fifty-one of 59 MDR-TB strains additionally resistant to streptomycin contained a mutation in the target genes analysed (Table 1), many of which have been described previously [23, 28]. These included 44 isolates with a mutation in rpsL (K43R, n = 33; K43T, n = 1; K88R, n = 5; K88T, n = 4; K88M, n = 1), four isolates with a mutation in rrs 500 or 900 region (A514C, n = 1; C517T, n = 1; G878A, n = 1 and A906G, n = 1) and three isolates with double mutation inrpsLandrrsgenes (rpsLK43R + rrsC527T, n = 1;rpsLK88T + rrsC517T, n = 1;rpsLK88R + rrsC602A, n = 1).
Incorrect: Resistance conferring mutations in rpsL and/or rrs gene were detected in majority (49 of 59, 83%) of streptomycin-resistant but not in any streptomycin-susceptible MDR-TB strain while mutations in embB gene were detected in both ethambutol-resistant and -susceptible MDR-TB strains, as described in our previous studies [23, 28].
Correct: Resistance conferring mutations in rpsL and/or rrs gene were detected in majority (51 of 59, 86.4%) of streptomycin-resistant but not in any streptomycin-susceptible MDR-TB strain while mutations in embB gene were detected in both ethambutol-resistant and -susceptible MDR-TB strains, as described in our previous studies [23, 28].
Incorrect: Phenotypic DST results for pyrazinamide were available for only 47 of 93 MDR-TB strains while the remaining 46 isolates failed to grow at lower pH. No pncA mutation was detected in 50 pansusceptible strains. Analysis of 93 MDR-TB strains showed that 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 46 isolates for which DST data for pyrazinamide was not available contained a mutation in pncA while all 11 MDR-TB strains phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.
Correct: Phenotypic DST results for pyrazinamide were available for only 46 of 93 MDR-TB strains while the remaining 47 isolates failed to grow at lower pH. No pncA mutation was detected in 50 pansusceptible strains. Analysis of 93 MDR-TB strains showed that 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 47 isolates for which DST data for pyrazinamide was not available contained a mutation in pncA while all 10 MDR-TB strains phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.
Incorrect: The two isolates in Cluster XII were also very closely related, with the second isolate (KM17-01) displaying an additional mutation (L95F) in gidB which is considered as a hot-spot for mutations in the M. tuberculosis genome [21, 57].
Correct: The two isolates in Cluster XII were also very closely related, with the second isolate (KM17-01) (Table 2) displaying an additional mutation (L59F) in gidB which is considered as a hot-spot for mutations in the M. tuberculosis genome [21, 57].
Footnotes
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Contributor Information
Noura M. Al-Mutairi, Email: noura.j@hsc.edu.kw
Suhail Ahmad, Email: suhail_ah@hsc.edu.kw.
Eiman M. Mokaddas, Email: e.mokaddas@hsc.edu.kw
Reference
- 1.Al-Mutairi NM, Ahmad S, Mokaddas EM. Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB. Eur J Med Res. 2019;24:38. doi: 10.1186/s40001-019-0397-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
