Dependence of Xpert MTB/RIF Accuracy for Detecting Rifampin Resistance in Bronchoalveolar Lavage Fluid on Bacterial Load: A Retrospective Study in Beijing, China

Lin Qin; Fengmin Huo; Weicong Ren; Yuanyuan Shang; Cong Yao; Xuxia Zhang; Rongmei Liu; Liping Ma; Mengqiu Gao; Yu Pang

doi:10.2147/IDR.S307488

Dependence of Xpert MTB/RIF Accuracy for Detecting Rifampin Resistance in Bronchoalveolar Lavage Fluid on Bacterial Load: A Retrospective Study in Beijing, China

Infect Drug Resist. 2021 Jun 28:14:2429-2435. doi: 10.2147/IDR.S307488. eCollection 2021.

Authors

Lin Qin^#¹, Fengmin Huo^#², Weicong Ren^#², Yuanyuan Shang², Cong Yao², Xuxia Zhang², Rongmei Liu³, Liping Ma³, Mengqiu Gao³, Yu Pang²

Affiliations

¹ Department of Endoscopic Diagnosis & Treatment, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China.
² Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China.
³ Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: We assessed the effect of Mycobacterium tuberculosis (MTB) bacterial load on Xpert MTB/RIF accuracy for detection of rifampicin (RIF)-resistant MTB in bronchoalveolar lavage fluid (BALF) specimens obtained at a national tuberculosis (TB) specialized hospital in Beijing, China.

Methods: A retrospective study was conducted at Beijing Chest Hospital. Patients with symptoms suggestive of pulmonary TB who provided BALF specimens for routine MTB detection between June 2019 and July 2020 were enrolled in the study. Chi-square test and Student's t-test were used to compare results across groups stratified according to BALF bacterial load.

Results: In total, 1125 patients with positive Xpert results who were enrolled in final analysis, 263 provided BALF specimens that tested positive for RIF-resistant MTB via Xpert MTB/RIF. The RIF-resistance rate of specimens with very low MTB bacterial load was 30.9%, a resistance rate significantly greater than rates obtained for groups with high (25.0%), medium (17.3%) and low (19.2%) MTB loads (P<0.01). Notably, false-positive results obtained for the very low bacterial load group led to markedly reduced positive predictive value of Xpert MTB/RIF to provide correct RIF-resistance predictions for that group (67.1%, 95% CI: 56.1%-78.1%5) relative to the predictive value obtained for all other groups combined (about 90%, P<0.05). Sanger sequencing data obtained for 20 (32.8%) MTB isolates deemed RIF-resistant via Xpert (Probe E) lacked rpoB RRDR mutations. Meanwhile, of another group of 23 isolates deemed RIF-susceptible via DST but RIF-resistant via Xpert MTB/RIF, 20 isolate sequences (87.0%) lacked rpoB RRDR mutations, while sequences of the remaining 3 isolates harbored single rpoB RRDR mutations predicted to cause amino acid substitutions.

Conclusion: Xpert MTB/RIF assay performed alarmingly poorly when used to detect RIF-resistant MTB in BALF specimens with very low bacterial loads. A high rate of Xpert probe E hybridization failure was the main driver of false-positive RIF-resistant results.

Keywords: China; Xpert MTB/RIF; bronchoalveolar lavage fluid; rifampicin.

Grants and funding

This study was funded by Beijing Hospitals Authority Ascent Plan (DFL20191601), and Major Science and Technology Project of the 13thFive-Year Plan (2018ZX10302302003). The funders had no role in study design, data collection, analysis, interpretation or writing of the report.