title: Diagnostic Performance of the New Version (v2.0) of GenoType MTBDRsl Assay for Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs: a Multicenter Study.
abstract: Resistance to fluoroquinolones (FLQ) and second-line injectable drugs (SLID) is steadily increasing, especially in eastern European countries, posing a serious threat to effective tuberculosis (TB) infection control and adequate patient management. The availability of rapid molecular tests for the detection of extensively drug-resistant TB (XDR-TB) is critical in areas with high rates of multidrug-resistant TB (MDR-TB) and XDR-TB and limited conventional drug susceptibility testing (DST) capacity. We conducted a multicenter study to evaluate the performance of the new version (v2.0) of the Genotype MTBDRsl assay compared to phenotypic DST and sequencing on a panel of 228 Mycobacterium tuberculosis isolates and 231 smear-positive clinical specimens. The inclusion of probes for the detection of mutations in the eis promoter region in the MTBDRsl v2.0 test resulted in a higher sensitivity for detection of kanamycin resistance for both direct and indirect testing (96% and 95.4%, respectively) than that seen with the original version of the assay, whereas the test sensitivities for detection of FLQ resistance remained unchanged (93% and 83.6% for direct and indirect testing, respectively). Moreover, MTBDRsl v2.0 showed better performance characteristics than v1.0 for the detection of XDR-TB, with high specificity and sensitivities of 81.8% and 80.4% for direct and indirect testing, respectively. MTBDRsl v2.0 thus represents a reliable test for the rapid detection of resistance to second-line drugs and a useful screening tool to guide the initiation of appropriate MDR-TB treatment.
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tagliani
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cabibbe
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Miotto
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Borroni
authors.affiliation: Unit for Highly Pathogenic Bacteria, Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Toro
authors.affiliation: Unit for Highly Pathogenic Bacteria, Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Mansjö
authors.affiliation: Unit for Highly Pathogenic Bacteria, Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.affiliation: Diagnostic Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hillemann
authors.affiliation: Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus.
authors.forename: Aksana
authors.initials: A
authors.lastname: Zalutskaya
authors.affiliation: Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus.
authors.forename: Alena
authors.initials: A
authors.lastname: Skrahina
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy cirillo.daniela@hsr.it.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Cirillo
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones