Preview

Antibiot Khimioter = Antibiotics and Chemotherapy

Advanced search

Tolerability of Linezolid in Individualized Chemotherapy Regimens for Adolescents with Multi- or Pre-Extensively Drug-Resistant Tuberculosis

https://doi.org/10.37489/0235-2990-2025-70-5-6-21-26

EDN: WWJRUQ

Abstract

   Background. The effectiveness of treatment for multidrug-resistant (MDR)/pre-extensively drug-resistant (pre-XDR) TB directly depends on the tolerability of chemotherapy, including linezolid, a group A drug.

   Aim: To study the incidence and types of adverse drug reactions (ADRs) to linezolid and ways to improve them in adolescents with MDR/pre-XDR TB.

   Methods. A retrospective study included 38 patients aged 13–17 years with various forms of pulmonary TB: MDR TB — 52.6 %, pre-XDR TB — 42.1 %, XDR TB — 5.3 %. The levels of eosinophils, hemoglobin, erythrocytes, leukocytes; ALT, AST were assessed. The immunological study (lymphocyte blast-transformation reaction) was performed to evaluate linezolid tolerability. ADRs were assessed by type (allergic, toxic, toxicoallergic) and severity.

   Results. The development of ADRs to linezolid was registered in 34.2 % of cases with prevailing toxic reactions (76.9 %). The most frequent reaction was anemia (46.2 %), ADRs of severity levels 1–2 were registered in 80 % of cases. ADRs were immunologically confirmed in 30.8 % of thecases — in patients with allergic, as well as both toxic and allergic reactions. In 84.6% of cases, short-term withdrawal of linezolid and symptomatic treatment were required.

   Conclusion. Despite the high frequency of ADRs induced by linezolid administration, most of them were mild and could be corrected without long-term drug withdrawal.

About the Authors

L. V. Panova
Central Tuberculosis Research Institute
Russian Federation

Lyudmila V. Panova, D. Sc. in Medicine, Leading Researcher

Child and Adolescent Department

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



E. A. Krushinskaya
Central Tuberculosis Research Institute
Russian Federation

Ekaterina A. Krushinskaya, Ph. D. in Medicine, Researcher

Child and Adolescent Department

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



E. S. Ovsyankina
Central Tuberculosis Research Institute
Russian Federation

Elena S. Ovsyankina, D. Sc. in Medicine, Professor, Head of
the Department

Child and Adolescent Department

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



M. M. Averbakh
Central Tuberculosis Research Institute
Russian Federation

Mikhael M. Averbakh, D. Sc. in Medicine, Chief Researcher

Department of Immunology

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



T. G. Smirnova
Central Tuberculosis Research Institute
Russian Federation

Tatiana G. Smirnova, Ph. D. in Medicine, Head of the Department

Microbiology Department

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



S. N. Andreevskaya
Central Tuberculosis Research Institute
Russian Federation

Sofya N. Andreevskaya, Ph. D. in Medicine, Leading Researcher

Microbiology Department

Moscow


Competing Interests:

The authors declare that there is no conflict of interest.



References

1. Zhou C. C., Swaney S. M., Shinabarger D. L., Stockman B. J. 1H nuclear magnetic resonance study of oxazolidinone binding to bacterial ribosomes. Antimicrob Agents Chemother. 2002; 46: 625–629. doi: 10.1128/aac.46.3.625-629.2002.

2. Leach K. L., Swaney S. M., Colca J. R., McDonald W.G., Blinn J. R., Thomasco L. M. et al. The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol Cell. 2007; 26: 393–402. doi: 10.1016/j.molcel.2007.04.005.

3. Eimer J., Frechet-Jachym M., Le Du D., Caumes E., El-Helali N., Marigot-Outtandy D. et al. Association Between Increased Linezolid Plasma Concentrations and the Development of Severe Toxicity in Multidrug-Resistant Tuberculosis Treatment. Clin Infect Dis. 2023; 76 (3): e947–e56. doi: 10.1093/cid/ciac485.

4. Zhang Z., Cheng Z., Liu Q., Shang T., Jiang L., Fu Z. et al. Safety of longer linezolid regimen in children with drug-resistant tuberculosis and extensive tuberculosis in Southwest China. J Glob Antimicrob Resist. 2020; 21: 375–379. doi: 10.1016/j.jgar.2019.09.019.

5. Zubova E. D., Tokhtakhodzhaeva G. R., Kiselyevich O. K., Yusubova A. N. The effectiveness of chemotherapy regimens with the inclusion of linezolid in children and teenagers with tuberculosis. Tuberculosis and socially significant diseases. 2023; 4 (44): 39–46. doi: 10.54921/2413-0346-2023-11-4-39-46. (in Russian)

6. Prieto L. M., Santiago B., Del Rosal T., Carazo B., Jiménez A. B., Pérez-Gorricho B. et al. Spanish Paediatric TB Research Network (pTBred). Linezolid-containing Treatment Regimens for Tuberculosis in Children. Pediatr Infect Dis J. 2019; 38 (3): 263–267. doi: 10.1097/INF.0000000000002093.

7. Yukhimenko N. V., Gubkina M. F., Sterlikova S. S. Tolerability of TB treatment in children. CTRI Bulletin. 2024; 0 (1): 34–42. doi: 10.57014/2587-6678-2024-0-1-34-42. (in Russian)

8. Clinical guidelines «Tuberkulyoz u detej» Russian Society of Phthisiologists. (in Russian) https://rof-tb.ru/upload/iblock/a34/ens4ys2ldl7tc0d3s1eo05rcvdiv58hr.pdf

9. WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. WHO, 2022, 128 р. Available from: https://www.who.int/publications/i/item/9789240046764.

10. Division of Microbiology and Infection Diseases (DMID) adult toxicity table. National Institute of Allergy and Infectious Diseases, Bethesda, 2007. Available from: http://www.niaid.nih.gov/LabsAndResources/resources/DMIDClinRsrch/Documents/dmidadulttox.pdf.

11. Okada R., Nakachi S., Inokuma S. The severity of peripheral blood eosinophilia indicates an eosinophilia-associated disease corresponding to its level. Allergol Int. 2016; 65 (1): 112–4. doi: 10.1016/j.alit.2015.07.006.

12. Patent R. U.S № 2772058/ 16.05.2022 г. Byul. № 14. Ovsyankina E. S., Panova L. V., Krushinskaya E. A., Chiteva A. Yu., Piskunova O. A., Poluektova F. A. i dr. Sposob lecheniya tuberkuleza organov dyhaniya u detej i podrostkov pri vozniknovenii pobochnyh reakcij (in Russian) https://elibrary.ru/download/elibrary_64606287_78521401.PDF.

13. Imperial M. Z., Nedelman J. R., Conradie F., Savic R. M. Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis. Clin Infect Dis. 2022; 74 (10): 1736–1747. doi: 10.1093/cid/ciab699.

14. Song T., Lee M., Jeon H. S., Park Y., Dodd L. E., Dartois V. et al. Linezolid trough concentrations correlate with mitochondrial toxicity-related adverse events in the treatment of chronic extensively drug-resistant tuberculosis. EBioMedicine. 2015; 2 (11): 1627–33. doi: 10.1016/j.ebiom.2015.09.051.

15. Garcia-Prats A. J., Schaaf H. S., Draper H. R., Garcia-Cremades M., Winckler J., Wiesner L. et al. Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: Combined data from two prospective observational studies. PLoS Med. 2019; 16 (4): e1002789. doi: 10.1371/journal.pmed.1002789.

16. Zhang X., Falagas M. E., Vardakas K. Z., Wang R., Qin R., Wang J. et al. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. J Thorac Dis, 2015; 7: 603–615. doi: 10.3978/j.issn.2072-1439.2015.03.10.

17. McKee E.E., Ferguson M., Bentley A. T., Marks T. A. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006; 50 (6): 2042–9. doi: 10.1128/AAC.01411-05.

18. Harausz E. P., Garcia-Prats A. J., Seddon J. A., Schaaf H. S., Hesseling A. C., Achar J. et al. Sentinel Project on Pediatric Drug-Resistant Tuberculosis. New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations. Am J Respir Crit Care Med. 2017; 195 (10): 1300–1310. doi: 10.1164/rccm.201606-1227CI.


Review

For citations:


Panova LV, Krushinskaya EA, Ovsyankina ES, Averbakh MM, Smirnova TG, Andreevskaya SN. Tolerability of Linezolid in Individualized Chemotherapy Regimens for Adolescents with Multi- or Pre-Extensively Drug-Resistant Tuberculosis. Antibiotiki i Khimioterapiya = Antibiotics and Chemotherapy. 2025;70(5-6):21-26. (In Russ.) https://doi.org/10.37489/0235-2990-2025-70-5-6-21-26. EDN: WWJRUQ

Views: 282

JATS XML


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0235-2990 (Print)