Disputed &lt;I&gt;rpo&lt;/I&gt;B mutations can frequently cause important rifampicin resistance among new tuberculosis patients

Deun, Armand Van; Aung, K. J. M.; Hossain, Anwar; Rijk, Pim de; Gumusboga, Mourad; Rigouts, Leen; Jong, Bouke C. de

doi:10.5588/ijtld.14.0651

Cited by 89 publications

(73 citation statements)

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“…In contrast, a portion of the isolates with intermediate resistance and substitutions in codons 516 and 526 were identified as susceptible by Bactec MGIT 960, which was in line with previous reports [12]. Previous reports noted the clinical importance of “disputed” mutations in the rpoB gene [34, 35, 36]. Because the standard treatment of these patients might result in a poor clinical outcome [37, 38], the use of higher doses of RMP [25] or substitution with RFB [39] is proposed.…”

Section: Discussionsupporting

confidence: 87%

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

Nosova¹,

Zimenkov

Khakhalina³

et al. 2016

PLoS ONE

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BackgroundThe goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region.MethodsA total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol.ResultsThe average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms.ConclusionsThe quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.

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Section: Discussionsupporting

confidence: 87%

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

Nosova¹,

Zimenkov

Khakhalina³

et al. 2016

PLoS ONE

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“…In addition, molecular studies indicate that it is also important to take into consideration the geographic distribution of different mutation types. It has been shown that in several regions, less common mutations can be significantly more common, and commercial molecular tests may not always detect these mutations (12,13). If the type of mutation is not known to the laboratory scientist or the clinician, it is not possible to draw meaningful conclusions for designing an appropriate drug regimen.…”

Section: (Ii) Is It Important To Have Information On the Type Mutatiomentioning

confidence: 99%

“…In addition, it is clear that some of these less common mutations, which may reach 22% of all RIF-resistant cases in certain areas (14,15), are associated with a phenotypic RIF resistance of Ͻ1.0 g/ml, which is also the definition criteria for MDR-TB. Preliminary results indicate that patients with such mutant strains may fail more often under firstline therapy with standard RIF doses (13). Therefore, future molecular tests must be able to adequately identify these mutations as well.…”

Section: (Ii) Is It Important To Have Information On the Type Mutatiomentioning

confidence: 99%

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

Somoskövi

2015

J Clin Microbiol

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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...

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“…[72] However, the general problem faced at the moment is that the predictive value of resistance mutations is not always clear, especially when they are rarely encountered. [73] For the frequently observed mutations tested in reverse line blot assays, such as the ones associated with rifampicin and isoniazid, the positive-and negative-predictive value is high and this merits direct clinical use of these test results to steer the treatment. [74] For other drugs, especially of the second-line category (Table 2), the predictive value is sometimes somewhat lower and this confuses the utility of this information.…”

Section: Molecular Testingmentioning

confidence: 99%

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Zuur

Bolhuis

Anthony

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Areas covered: Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Expert opinion: Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment. ARTICLE HISTORY

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Disputed <I>rpo</I>B mutations can frequently cause important rifampicin resistance among new tuberculosis patients

Cited by 89 publications

References 0 publications

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

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

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

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