Utility of Mycobacterium tuberculosis PCR in ruling out active disease and impact on isolation requirements in a low prevalence setting

Abstract

Objective To analyze and interpret clinical microbiology data for specimens tested with the fluorochrome stain (AFB stain), mycobacterial culture and a laboratory-developed Mycobacterium tuberculosis (MTB) PCR in order to understand the performance of each test and to demonstrate the utility of MTB PCR to assist with decisions regarding discontinuation of airborne isolation. Methods Retrospective cohort analysis of 2798 respiratory specimens from 2006 patients in the period between November 1st, 2011 and January 1st, 2018. Results 53.7% were males, median age was 61 years, and 43 patients were HIV positive. Results demonstrated positive mycobacterial cultures for MTB in 52 specimens (1.9%) and for nontuberculous mycobacteria (NTM) or aerobic actinomycetes (eg., Nocardia spp.) in 435 specimens (16%). Using mycobacterial culture as the gold standard, AFB smear had a sensitivity of 48.1% while MTB PCR had a sensitivity of 96.0% in AFB smear positive specimens and an overall sensitivity of 57.7% with PPV of 94% and a NPV of 99%. Conclusions The combination of a positive AFB smear with a negative MTB PCR offers a rapid result to rule out active pulmonary MTB in a low prevalence setting. In this study, that combination reliably excluded active tuberculosis (NPV of 99.2%). The combination of a positive AFB smear with a negative MTB PCR indicated pulmonary NTM infection with the results available within 1 day. There was little benefit to pursuing collection and testing of more than 2 respiratory specimens in a low prevalence setting for both long term diagnostic or rapid isolation discontinuation purposes.

Prevalence of non-tuberculous mycobacteria among people presumed to have tuberculosis, positive for acid-fast bacilli in Mali

“…The higher positivity rate by qPCR compared to the conventional nested PCR we observed in our study could be partially attributable to the non-specificity of the 16S primers employed for the in-house qPCR which also detects species belonging to closely related genera like Rhodococcus and Nocardia , hence potentially overestimating the NTM rate. These closely related species indeed can be detected in smear-positive samples not containing tubercle bacilli, such as documented in the USA with 78.4% (134/171) of AFB-positive specimens yielding a positive culture with NTM or Nocardia spp, while 14.6% (25/171) of AFB-positive specimens grew MTBc and another 7% (12/171) remained negative in culture (20). The proportion of NTM versus Nocardia spp note the clinical relevance of these isolated bacteria were discussed in that study.…”

Second Time's the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting

“…Our findings regarding the low yield of a third smear in the assessment for pulmonary tuberculosis are consistent with a systematic review, which found that the incremental yield of a third smear was only 2.3% [ 20 ]. A recent study from the Mayo Clinic concluded that collecting >2 respiratory specimens did not lead to any additional tuberculosis diagnoses [ 21 ]. Collecting a third specimen contributes to patient time in airborne isolation, attendant bed capacity challenges, and strain on hospital laboratory resources.…”

Diagnostic value of bronchoscopy in sputum-negative pulmonary tuberculosis patients and its correlation with clinicoradiological features

“…58%). [ 42 43 ] Therefore, our results of BAL PCR yield should be read with caution since sputum PCR was not performed on all patients.…”