Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study

E. Cambau, M. Viveiros, D. Machado, L. Raskine, C. Ritter, E. Tortoli, V. Matthys, S. Hoffner, E. Richter, M. L. Perez Del Molino, D. M. Cirillo, D. Van Soolingen, E. C. Böttger

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Objectives: Treatment outcome of MDR-TB is critically dependent on the proper use of second-line drugs as per the result of in vitro drug susceptibility testing (DST). We aimed to establish a standardized DST procedure based on quantitative determination of drug resistance and compared the results with those of genotypes associated with drug resistance. Methods: The protocol, based on MGIT 960 and the TB eXiST software, was evaluated in nine European reference laboratories. Resistance detection at a screening drug concentration was followed by determination of resistance levels and estimation of the resistance proportion. Mutations in 14 gene regions were investigated using established techniques. Results: A total of 139 Mycobacterium tuberculosis isolates from patients with MDR-TB and resistance beyond MDR-TB were tested for 13 antituberculous drugs: isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, para-aminosalicylic acid, ethionamide, amikacin, capreomycin, ofloxacin, moxifloxacin and linezolid. Concordance between phenotypic and genotypic resistance was >80%, except for ethambutol. Time to results was short (median 10 days). High-level resistance, which precludes the therapeutic use of an antituberculous drug, was observed in 49% of the isolates. The finding of a low or intermediate resistance level in 16% and 35% of the isolates, respectively, may help in designing an efficient personalized regimen for the treatment of MDR-TB patients. Conclusions: The automated DST procedure permits accurate and rapid quantitative resistance profiling of firstand second-line antituberculous drugs. Prospective validation is warranted to determine the impact on patient care.

Original languageEnglish
Article numberdku438
Pages (from-to)686-696
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Antibiotic susceptibility testing
  • Antituberculous drugs
  • DST
  • MGIT
  • TB eXiST

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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