Volume 31, Number 3—March 2025
Dispatch
Outbreak Caused by Multidrug-Resistant Mycobacterium Tuberculosis with Unusual Combination of Resistance Mutations, Northern Argentina, 2006–2022
Table 2
Resistance conferring mutations found in Ch strain isolates from patients with MDR-TB infection, Argentina, 2006–2022*
| Mutation | Drug | Confidence grading | Phenotype/genotype† | Concordance |
|---|---|---|---|---|
| rpoB_Asp435His |
RIF |
Associated with resistance–interim |
24/24 |
Yes |
| rpoB_His445Asp |
RIF |
Associated with resistance |
24/24 |
Yes |
| fabG1-inhA_t-8c | INH | Associated with resistance–interim | 24/24 | Yes |
| ETH |
Associated with resistance–interim |
3/24‡ |
Partial |
|
| katG_Ser315Thr |
INH |
Associated with resistance |
24/24 |
Yes |
| embB_Met306Ile |
EMB |
Associated with resistance |
18/24§ |
Partial |
| embA_c-11a |
EMB |
Uncertain significance |
NA |
NA |
| pncA_Pro54Leu |
PZA |
Associated with resistance |
24/24 |
Yes |
| rpsL_Lys43Arg |
STR |
Associated with resistance |
24/24 |
Yes |
| rrs_a1401 g | KAN | Associated with resistance | 1/1 | Yes |
| AMK | Associated with resistance | 1/1 | Yes | |
| CAP |
Associated with resistance |
1/1 |
Yes |
|
| eis_c-14t | KAN | Associated with resistance | 1/1 | Yes |
| AMK | Associated with resistance–interim | 0/1 | No | |
| CAP |
NA |
0/1 |
NA |
|
| tlyA_Arg18stop (LoF) | KAN | NA | 0/1 | NA |
| AMK | NA | 0/1 | NA | |
| CAP |
Associated with resistance |
1/1 |
Yes |
|
| gyrA_Asp94Ala |
FLQ |
Associated with resistance |
10/10¶ |
Yes |
| rrl_g2270t |
LZD |
Associated with resistance–interim |
1/1# |
Yes |
| Rv0678_144dupC (LoF) | BDQ | Associated with resistance | 1/1 | Yes |
| CFZ | Associated with resistance | 1/1** | Yes |
*Confidence grading according to the World Health Organization Catalogue of Mutations, 2nd Edition (3). AMK, amikacin; BDQ, bedaquiline; CAP, capreomycin; CFZ, clofazimine; EMB, ethambutol; ETH, ethionamide; FLQ, fluoroquinolone; INH, isoniazid; LoF, loss of function; LZD, linezolid; NA, not applicable; PZA, pyrazinamide; RIF, rifampin; Stop, stop codon; STR, streptomycin; 2LI, second-line injectable drugs.†For the isolates studied by whole-genome sequencing; phenotypically resistant isolates/isolates harboring each mutation are indicated. ‡Fifteen isolates were sensitive, 5 isolates had discordant results between methods, and 1 isolate was not tested. §Two isolates were susceptible, 3 had discordant results between proportion and MGIT methods, and 1 isolate was not studied. ¶Resistance to low dose of moxifloxacin. #Isolate 6.4 had a MIC of 4 mg/L for LZD (suggested cutoff value 0.5 mg/L). **Isolate 10.4 had a MIC of 2 mg/L for CFZ (suggested cutoff value 0.25 mg/L). Phenotypic resistance to BDQ was implemented in 2021, and isolate 10.4. was tested in the light of the genomic results.
References
- Argentina Ministerio de Salud. Boletín N° 7 tuberculosis y lepra en la argentina coordinación de tuberculosis y lepra [cited 2024 Nov 30]. https://www.argentina.gob.ar/sites/default/files/2024/04/boletin_tuberculosis_2024_1642024.pdf
- Ritacco V, López B, Ambroggi M, Palmero D, Salvadores B, Gravina E, et al.; National TB Laboratory Network. HIV infection and geographically bound transmission of drug-resistant tuberculosis, Argentina. Emerg Infect Dis. 2012;18:1802–10. DOIPubMedGoogle Scholar
- World Health Organization. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, 2nd ed. [cited 2024 Nov 30]. https://www.who.int/publications/i/item/9789240082410
- Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJM. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 2006;312:1944–6. DOIPubMedGoogle Scholar
- Yokobori N, Paul R. Informe técnico sobre la tuberculosis multidrogorresistente en la Argentina, 2023 [cited 2024 Nov 30]. https://sgc.anlis.gob.ar/handle/123456789/2618
- Monteserin J, Paul R, Gravina E, Reniero A, Hernandez T, Mazzeo E, et al. Genotypic diversity of Mycobacterium tuberculosis in Buenos Aires, Argentina. Infect Genet Evol. 2018;62:1–7. DOIPubMedGoogle Scholar
- Comín J, Cebollada A, Ibarz D, Viñuelas J, Vitoria MA, Iglesias MJ, et al. A whole-genome sequencing study of an X-family tuberculosis outbreak focus on transmission chain along 25 years. Tuberculosis (Edinb). 2021;126:
102022 . DOIPubMedGoogle Scholar - Bishai WR, Dannenberg AM Jr, Parrish N, Ruiz R, Chen P, Zook BC, et al. Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in rabbits evaluated by Lurie’s pulmonary tubercle count method. Infect Immun. 1999;67:4931–4. DOIPubMedGoogle Scholar
1These first authors contributed equally to this article.