What is resistance? Impact of phenotypic versus molecular drug resistance testing on therapy for multi-and extensively drug-resistant tuberculosis

by Jan Heyckendorf, Sönke Andres, Claudio U Köser, Ioana D Olaru, Thomas Schön, Erik Sturegård, Patrick Beckert, Viola Schleusener, Thomas A Kohl, Doris Hillemann, Danesh Moradigaravand, et al.
Research Article Year: 2018

Extra Information

Antimicrobial agents and chemotherapy, 62(2) e01550-17

Abstract

Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0) and whole-genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged …