Whole-Genome Sequencing for Predicting Clarithromycin Resistance in .

Lipworth, Samuel, Hough, Natasha, Leach, Laura, Morgan, Marcus, Jeffery, Katie, Andersson, Monique, Robinson, Esther, Smith, E Grace, Crook, Derrick, Peto, Tim and Walker, Timothy (2019) Whole-Genome Sequencing for Predicting Clarithromycin Resistance in . Antimicrobial agents and chemotherapy, 63 (1). ISSN 1098-6596. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.

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Official URL: https://aac.asm.org/content/63/1/e01204-18.long

Abstract

is emerging as an important pathogen in chronic lung diseases, with concern regarding patient-to-patient transmission. The recent introduction of routine whole-genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterize the genetic determinants of resistance. We conducted a systematic review to catalogue all known resistance-determining mutations. This knowledge was used to construct a predictive algorithm based on mutations in the (41) and genes which was tested on a collection of 203 sequentially acquired clinical isolates for which there were paired genotype/phenotype data. A search for novel resistance-determining mutations was conducted using a heuristic algorithm. The sensitivity of existing knowledge for predicting resistance in clarithromycin was 95% (95% confidence interval [CI], 89 to 98%), and the specificity was 66% (95% CI, 54 to 76%). The subspecies alone was a poor predictor of resistance to clarithromycin. Eight potential new resistance-conferring single nucleotide polymorphisms (SNPs) were identified. WGS demonstrated probable resistance-determining SNPs in regions that the NTM-DR line probe cannot detect. These mutations are potentially clinically important, as they all occurred in samples that were predicted to be inducibly resistant and for which a macrolide would therefore currently be indicated. We were unable to explain all resistance, raising the possibility of the involvement of other as yet unidentified genes.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.
Subjects: QZ Pathology. Oncology
WF Respiratory system. Respiratory medicine
Divisions: Clinical Support > Pathology
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Depositing User: Mrs Noomi Tyholdt-Pidgley
Date Deposited: 06 May 2020 14:34
Last Modified: 06 May 2020 14:34
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3049

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