British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

Haworth, Charles; Banks, John; Capstick, Toby; Fisher, Andrew J.; Gorsuch, T; Laurenson, Ian F.; Leitch, Andrew; Loebinger, Michael R.; Milburn, Heather; Nightingale, M. J.; Ormerod, Peter; Shingadia, Delane; Smith, David L.; Whitehead, Nuala; Wilson, Robert; Floto, Andres

doi:10.1136/bmjresp-2017-000242

Cited by 107 publications

(157 citation statements)

References 4 publications

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“…8 Similarly, as the absence of a functional erm(41) gene has been associated with good therapeutic outcomes its molecular detection ought to be beneficial to patients, 7 although in our study this alone was .…”

Section: Discussionmentioning

confidence: 57%

“…7 However, the American Thoracic Society/Infectious Diseases Society of America and British Thoracic Society (ATS/IDSA and BTS) guidelines recommend including a macrolide in treatment regimens where samples are either susceptible, or demonstrate inducible resistance. 8,9 Whole genome sequencing has been implemented in stages across England since December 2016, replacing existing reference techniques for mycobacterial identification. As a consequence, there is now the opportunity to explore the molecular determinants of drug resistance for all clinical NTM isolates, as has been successfully achieved in a range of different bacteria.…”

Section: Introductionmentioning

confidence: 99%

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Whole genome sequencing for predicting clarithromycin resistance in Mycobacterium abscessus

Lipworth

Hough

Leach

et al. 2018

Preprint

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Objectives:Mycobacterium abscessus 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 characterise the genetic determinants of resistance. Methods:A systematic review was performed to catalogue all known resistance determining mutations. This knowledge was used to construct a predictive algorithm which was tested on a collection of 209 sequentially acquired clinical isolates for which there was paired genotype/phenotype data. Predictions were made for those drugs for which genetic loci involved in drug resistance were identified in the literature search. A search for novel resistance determining mutations was conducted using an heuristic algorithm. Results:The literature search identified two genes of interest for Clarithromycin (rrl and erm (41)) and Ciprofloxacin (gyrA and gyrB) and one for Amikacin (rrs). After excluding isolates predicted to be inducibly resistant and those for which there were null calls in key positions, the sensitivity of existing knowledge for clarithromycin was 76.19% (95% CI 52.8 -91.8%) and the specificity was 100%. Subspecies alone was a poor predictor of resistance to macrolides. For Ciprofloxacin the sensitivity was 0% and for Amikacin it was 5.0% (95% CI 2.0 -10.0). Seven potential new resistance conferring SNPs were identified for clarithromycin, four for ciprofloxacin and three for amikacin. Conclusion:We demonstrate that WGS demonstrates probable resistance determining SNPs in regions the NTM-DR line probe cannot detect. These mutations are potentially clinically important as they all occurred in samples 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.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing for predicting clarithromycin resistance in Mycobacterium abscessus

Lipworth

Hough

Leach

et al. 2018

Preprint

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“…Wichtig ist daher die korrekte Diagnosefindung unter Berücksichtigung der klinischen, radiologischen und mikrobiologischen Befunde anhand der IDSA/ATS-Leitlinie bzw. den Guidelines der British Thoracic Society (BTS) und der zu erwartenden neuen internationalen Leitlinie der verschiedenen Fachgesellschaften (ATS/IDSA, der European Respiratory Society [ERS] und European Society of Clinical Microbiology and Infectious Diseases [ESCMID]; [9,12] [32]. Von Untersuchungen bei Kin-dernmitakuterRSV-Infektionweißman, dass über eine Verknüpfung von Mikrobiom-mit Transkriptomdaten zur Wirtszellantwort der bei der Infektion involvierten Immunzellen Rückschlüsse auf den Schweregrad der Infektion gezogen werden können [30].…”

Section: Ntm-isolate Und -Erkrankungen Zugenommenunclassified

Das neue Verständnis pulmonaler Infektionen

Hörster

Rupp

2019

Pneumologe

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“…The American Thoracic Society has recommended different groups of agents, namely, macrolides (clarithromycin), aminoglycosides (amikacin), cephamycins (cefoxitin), and carbapenems (imipenem), to treat M. abscessus infections [4]. Moxifloxacin (MFX) emerged as pnromising candidates for the treatment of RGM infections [4,12,13]. It showed good activity in vitro against M. abscessus [14] and was suggested as one of the antibiotic regimens for adults with M. abscessus disease [12].…”

Section: Introductionmentioning

confidence: 99%

Moxifloxacin efficacy againstMycobacterium abscessus in vivousing zebrafish model

Nie

Gao

Teng

et al. 2019

Preprint

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Moxifloxacin (MFX) showed good activity in vitro against Mycobacterium abscessus (M. abscessus) and was suggested as one of the antibiotic regimens for adults with M. abscessus disease. However, some other studies showed that MFX showed less or none activity against M. abscessus. In our study we aim to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. MIC of each drugs were determined by broth microdilution method. M. abscessus labeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activity in vitro. But in vivo MFX showed limited restriction to M. abscessus. The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy on Mycobacterium abscessus in vivo using ZF model. MFX’s activity in vivo need to be confirmed.

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British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

Abstract: The full guideline for the management of non-tuberculous mycobacterial pulmonary disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.

Cited by 107 publications

References 4 publications

Whole genome sequencing for predicting clarithromycin resistance in Mycobacterium abscessus

Whole genome sequencing for predicting clarithromycin resistance in Mycobacterium abscessus

Das neue Verständnis pulmonaler Infektionen

Moxifloxacin efficacy againstMycobacterium abscessus in vivousing zebrafish model

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