Impact of GeneXpert MTB/RIF assay on triage of respiratory isolation rooms for inpatients with presumed tuberculosis: a hypothetical trial

Abstract

Background: Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms.

Methods: We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies.

Results: Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours).

Conclusions: Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals.

Keywords: GeneXpert; infection control; molecular diagnostic techniques; tuberculosis.

Figure 1.

Study enrollment flow diagram. ^aIncludes 6 samples rejected for culture because >3 days had elapsed since collection, 4 samples that were not tested for reasons that were not documented, 2 specimens that arrived when the Xpert machine was not operating because it was undergoing routine maintenance, and 1 specimen that was not one of the first 2 samples collected. ^bThree patients provided specimens for the study on 2 separate admissions, with each episode analyzed independently. Abbreviations: AFB, acid-fast bacilli; Xpert, Gene Xpert MTB/RIF assay.

Figure 2.

Horizontal boxplots showing distributions of completion times for each step in sputum examination by concentrated acid-fast bacilli smear microscopy for all inpatient evaluation episodes (n = 142). Horizontal boxplots show medians and interquartile ranges (IQRs), with whisker plots displaying lower and upper adjacent values (values inside 1.5 × IQR). In addition, the median values are provided as text at the right side of the plot. Three patients were admitted twice, giving 139 patients and 142 observations.