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Establishing of drug susceptibility testing to Pretomanid

E Richter(1) S Geiger(1) J Koglin(1)

1:Labor Limbach; 2:TB-Laboratory

Pretomanid has recently been proposed as a new anti TB-drug.  Together with Bedaquiline, Linezolid, and Moxifloxacin it is one component of the revolutionary new six‑months treatment regimen (BPaLM) recommended by WHO. Meanwhile this regimen is implemented in several regional treatment guidelines, as in Germany. To guide clinicians and to be prepared for surveillance of drug resistance to Pretomanid, we aimed to establish a robust drug susceptibility testing (DST) in our laboratory. We used the BACTEC MGIT 960 system in combination with the EpiCenter™/TB eXiST™software, that enables rapid drug susceptibility testing using any drug and drug concentration.

For establishing DST to Pretomanid we obtained pure drug from the The Global Alliance for TB

Drug Development. For preliminary MIC testing drug concentrations from 0.03 to 4.0 µg/ml in 2-fold dilutions were chosen, based on the study of Bateson et al. The H37Rv strain was included as control strain. Since differences in MIC values have been described for the various M. tuberculosis lineages as well as the animal adapted TB strains and M. canetti, we included TB strains from lineages 1 to 4 as well as M. bovis and M. africanum. Furthermore, we compared MIC values starting from solid culture (Löwenstein-Jensen) vs. MGIT liquid culture. We could confirm differences in MIC values between lineage 1 and the other TB strains and we additionally established a protocol to start from liquid MGIT medium to be able to include the Pretomanid DST into the routine DST together with other second line drugs.

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