Probability of Negative Mycobacterium tuberculosis Complex Cultures Based on Time to Detection of Positive Cultures: a Multicenter Evaluation of Commercial-Broth-Based Culture Systems

Abstract

We conducted a multicenter study to determine whether Mycobacterium tuberculosis complex (MTBC) cultures in automated broth-based systems could reliably be considered negative sooner than 6 weeks. Laboratory sites used Bactec MGIT or BacT/Alert and tracked results of time to detection of all mycobacteria (TTD-all, n = 1547) and of MTBC (TTD-MTBC, n = 466) over 6-month periods from primarily (93%) respiratory specimens. Cumulative percentages by day detected and median TTD of initial and follow-up specimens were analyzed. The median TTD-MTBC for MGIT ( n = 6 sites) was 14 days. For laboratories using standard processing procedures, 100% of MTBC were detected from initial and follow-up specimens in 28 and 35 days, respectively, and no yield of MTBC on solid or MGIT liquid media was observed after 5 weeks. The median TTD-MTBC for BacT/Alert ( n = 3 sites) was 18 days, with 95% and 100% detected within 37 and 42 days, respectively. Analysis of TTD of positive MTBC cultures in broth can predict the probability of culture negativity at defined time points. Receipt of interim negative reports earlier than 6 weeks could assist clinicians in considering alternative diagnoses and could alter the timing and prioritization of public health interventions. Laboratories should analyze their own TTD data to inform protocol decisions. Laboratories using MGIT could issue reports of no growth of MTBC on initial specimens as early as 4 weeks and for patients undergoing treatment as early as 5 weeks postinoculation.

Incubation time of Mycobacterium tuberculosis complex sputum cultures in BACTEC MGIT 960: 4weeks of negative culture is enough for physicians to consider alternative diagnoses

“…This may delay physician decisions and limit laboratory capacity. Studies from Switzerland and the U.S., low TB burden countries, suggested that the incubation time of MGIT cultures could be shortened from six weeks [9, 10]. We sought to test this hypothesis in a setting with a high incidence of TB and HIV infection.…”

“…Pfyffer and Wittwer in a smaller study from Switzerland found that 50% of their MGIT cultures for MTB complex became positive within 14 days, concluding that a final report of a negative culture could be issued after 4 weeks of incubation [9]. In a multicenter study of 366 MTB complex positive MGIT cultures done at 9 U.S. laboratories, Tyrrell et al reported that 99.4% of diagnostic specimens were detected by week 4, concluding that a negative culture could reliably be reported at 4 weeks for diagnostic specimens and 5 weeks for follow-up specimens [10]. Our analysis, based on a much larger number of MTB complex positive sputum cultures collected over 8 years in a high TB incidence country, confirms the findings of these studies.…”

Sputum induction is a safe procedure to use in prisoners and MGIT is the best culture method to diagnose tuberculosis in prisons: a cohort study

“…The time to detection of a positive culture with MGIT was found to be shorter than with LJ or TLA, in accordance with the results of previous studies. [5][6][7][8][9][10][11][12][13][14] Furthermore, Balabanova et al reported that the concordance between drug susceptibility testing on LJ and MGIT was 96.8% for rifampicin and 95.6% for isoniazid. 28 There are new molecular techniques that perform well, allowing diagnosis on the same day, with the added advantage of providing information about resistance to isoniazid and/or rifampicin.…”

“…These methods have been shown to decrease the mean time to detection of growth to 11-15.1 days. 5,6,9,[11][12][13][14] The method of obtaining a respiratory sample is also critical. In prisons, it is important to employ alternative strategies to obtain a specimen when the patient cannot expectorate or has inadequate sputum (HIV patients or those with a dry cough), during follow-up to confirm that the patient is cured, or for people who are sputum smear-negative.…”

Factors Associated with Missed Detection ofMycobacterium tuberculosisby Automated BACTEC MGIT 960 System

“…Rapid diagnosis of TB is critical for initiating effective treatment and preventing its transmission in the community [1]. Recent advances in molecular methods have shortened the turnaround time for the identification of Mycobacterium tuberculosis (MTB); however, culture is still essential for phenotypic drug susceptibility testing and improving the case detection of smear negative patients [1, 2]. Due to the slow growth rate, conventional solid culture systems including Löwenstein-Jensen (LJ) slant or Middlebrook 7H11 agar plate always require 8 weeks of incubation before a negative result is reported, which cannot meet the criteria of clinical practice [3].…”