Abstract
BackgroundDiagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management.ObjectivesTo determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB.MethodsRetrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500’000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation.ResultsAmong 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease.ConclusionsIn Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.
Highlights
Since the publication by Boehme et al of the contribution of rapid molecular diagnostic techniques for detecting TB, and their rapid implementation worldwide, the diagnosis of tuberculosis has changed dramatically (Boehme et al, 2010)
NAAT have increased the analytical sensitivity as compared to microscopy: they allow a positive diagnosis of tuberculosis within hours, while requiring only basic levels of laboratory skills
All strains were identified as M. tuberculosis except for one M. africanum, and four M. bovis
Summary
Since the publication by Boehme et al of the contribution of rapid molecular diagnostic techniques for detecting TB (referred to as NAAT: Nuclear acid amplification techniques), and their rapid implementation worldwide, the diagnosis of tuberculosis has changed dramatically (Boehme et al, 2010). NAAT have increased the analytical sensitivity as compared to microscopy (auramine stain and Ziehl-Neelsen for acid-fast bacilli: AFB): they allow a positive diagnosis of tuberculosis within hours, while requiring only basic levels of laboratory skills. Multicentric studies in high prevalence areas show that NAAT allow early identification in approximately 80% of all culture positive TB cases irrespective of microscopy (Theron et al, 2014; Calligaro et al, 2017). Boehme et al showed in a large multicentric field study that Xpert/MTB-RIF could detect 90.3% of culture positive samples (76.9% in smear negative samples) (Boehme et al, 2011). Diagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. When sample size does not allow performing both culture and Xpert, or if Xpert is negative, formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management
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