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

J Antimicrob Chemother. 2015 Mar;70(3):686-96. doi: 10.1093/jac/dku438. Epub 2014 Nov 11.


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 first- and second-line antituberculous drugs. Prospective validation is warranted to determine the impact on patient care.

Keywords: DST; MGIT; TB eXiST; antibiotic susceptibility testing; antituberculous drugs.

Publication types

  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Europe
  • Genotyping Techniques / methods
  • Humans
  • Microbial Sensitivity Tests / methods*
  • Microbial Sensitivity Tests / standards
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development*
  • Mycobacterium tuberculosis / isolation & purification
  • Tuberculosis, Multidrug-Resistant / microbiology*


  • Antitubercular Agents