Added value of whole-genome sequencing for management of highly drug-resistant TB.

Autor:	Outhred AC; Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research-Pathology West, Sydney, Australia Children's Hospital at Westmead, Sydney, Australia alexander.outhred@health.nsw.gov.au., Jelfs P; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research-Pathology West, Sydney, Australia Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia., Suliman B; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research-Pathology West, Sydney, Australia Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia., Hill-Cawthorne GA; Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia., Crawford AB; Department of Respiratory and Sleep Medicine, Liverpool Hospital, Sydney, Australia., Marais BJ; Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia Children's Hospital at Westmead, Sydney, Australia., Sintchenko V; Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research-Pathology West, Sydney, Australia Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2015 Apr; Vol. 70 (4), pp. 1198-202. Date of Electronic Publication: 2014 Dec 09.
DOI:	10.1093/jac/dku508
Abstrakt:	Objectives: Phenotypic drug susceptibility testing (DST) for Mycobacterium tuberculosis takes several weeks to complete and second-line DST is often poorly reproducible, potentially leading to compromised clinical decisions. Following a fatal case of XDR TB, we investigated the potential benefit of using whole-genome sequencing to generate an in silico drug susceptibility profile. Methods: The clinical course of the patient was reviewed, assessing the times at which phenotypic DST data became available and changes made to the therapeutic regimen. Whole-genome sequencing was performed on the earliest available isolate and variants associated with drug resistance were identified. Results: The final DST report, including second-line drugs, was issued 10 weeks after patient presentation and 8 weeks after initial growth of M. tuberculosis. In the interim, the patient may have received a compromised regimen that had the potential to select for further drug resistance. The in silico susceptibility profile, extrapolated from evolving evidence in the literature, provided comparable or superior data to the DST results for second-line drugs and could be generated in a much shorter timeframe. Conclusions: We propose routine whole-genome sequencing of all MDR M. tuberculosis isolates in adequately resourced settings. This will improve individual patient care, monitor for transmission events and advance our understanding of resistance-associated mutations. (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
Databáze:	MEDLINE
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