Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

Abstract

A ccording to the World Health Organization (WHO), there are many hot spots of multidrug-resistant tuberculosis (MDR-TB), defined as resistance to rifampin (RIF) and isoniazid (INH), in the world. In one of the hot spots, the Russian Federation, a total of 142,500 TB cases, including an estimated 41,000 MDR-TB pulmonary cases in 2013, were reported. Of all new TB cases, 19% were MDR-TB, and among retreated cases, 49% were MDR-TB cases (1). In contrast, the U.S. Centers for Disease Control and Prevention (CDC) reported 9,582 TB cases, including 96 MDR-TB cases in 2014, resulting in 1.3% of all TB cases with available antimicrobial susceptibility test (AST) results (2). The time has come to screen all TB cases in the United States for MDR-TB either at the time a sputum specimen tests positive with a nucleic acid amplification test (NAAT) or when the culture yields a positive result for Mycobacterium tuberculosis complex.The faster turnaround time for diagnosing MDR-TB, enabled by current molecular assays which yield results within hours compared to weeks and months with conventional testing, is needed in order to make up for lost time because of patient and/or health care system delays. An earlier diagnosis of MDR-TB facilitates earlier prescription of an adequate regimen benefiting patients and public health. However, in addition to screening all patients rapidly for MDR-TB, additional information is necessary from molecular assays for the successful management of MDR-TB patients.Besides the presence or absence of M. tuberculosis, the next additional answer from a routine rapid molecular test is whether the patient's specimen contains MDR-TB. In cases where MDR-TB is confirmed, the second question that such an assay will need to rapidly confirm is the presence of extensively drug-resistant tuberculosis (XDR-TB), which is defined as MDR-TB plus resistance to quinolones and second-line injectable drugs. IS RAPID CONFIRMATION OF THE FACT THAT THE PATIENT HAS MDR-OR XDR-TB ENOUGH OR DO WE NEED TO GO BEYOND WITH RAPID MOLECULAR SCREENING?In light of the accumulating evidence on the meaning of molecular mechanisms of different first-and second-line antituberculosis drugs, by appropriate characterization of known and newly identified resistance-associated mutations with quantitative phenotypic susceptibility testing, it is time to raise the question " is rapid detection of MDR and XDR-TB alone enough to successfully win the war on TB or MDR-TB?" Can we extract and utilize more meaningful diagnostic information from currently used molecular tests for our patients?In order to settle this question, we need to keep in mind that molecular markers cannot only rapidly confirm the presence of MDR-TB, they may also provide additional valuable information that can help to predict the level of phenotypic resistance or even cross-resistance to certain first-and second-line antituberculosis drugs. These molecular markers may provide such important additional information as to significantly influence the care of the patient and ultim...

Practical Guidance for Clinical Microbiology Laboratories: Mycobacteria

“…This significant number of patients with INH-resistant TB, if remaining unidentified, will be treated with only a single active drug during the continuation phase of their therapy, which will inevitably lead to MDR-TB. These few points highlight the importance of molecular INH resistance screening (156).…”

“…The Xpert assay is an FDA-cleared, rapid, real-time PCR test that simultaneously detects the presence of the M. tuberculosis complex and mutations in the RRDR of rpoB. RIF resistance detected by Xpert requires confirmation by additional AST methods (156) (see "Detection of Antimicrobial Resistance," above, for more information on the molecular detection of drug resistance and Table 10 for interpretation and reporting of Xpert results). Since many clinical laboratories may have an Xpert instrument for other tests, the implementation of the moderately complex Xpert test makes screening for RIF resistance more widely available.…”

Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers

“…The longer it takes for people to receive their results, the more time goes by where they might unwittingly infect others. Rapid turnaround time has previously been identified as critical in the diagnosis of other respiratory pathogens, such as tuberculosis (Somoskovi and Salfinger, 2015). For SARS-CoV-2 screening, turnaround time appears to be nearly as important as the frequency of screening, and more important than the assay limit of detection (Larremore et al, 2020).…”

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

“…The data strongly suggest that expanded studies, examining both phenotypic and genotypic data for a larger number of isolates from India and surrounding countries, should be conducted. Such studies would contribute to the development, refinement, and improvement of rapid molecular diagnostic tests for determining resistance (50). They would also aid in the control and identification of pre-XDR-TB and XDR-TB in a more timely and effective manner, preferably at the time of detection of MDR-TB.…”