The reliability of rifampicin resistance as a proxy for multidrug-resistant tuberculosis: a systematic review of studies from Iran

Nasiri, Mohammad Javad; Zamani, Samin; Pormohammad, Ali; Feizabadi, Mohammad M.; Aslani, Hamidreza; Amin, Mohsen; Halabian, Raheleh; Fooladi, Abbas Ali Imani

doi:10.1007/s10096-017-3079-4

Cited by 22 publications

(15 citation statements)

References 25 publications

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“…Therefore, it may be prudent, at least in lowincidence settings, to be cautious of using rpoB mutation as a proxy for MDR-TB. Resistance to isoniazid and to other first-line drugs should be confirmed before switching to a regimen with more serious side effects and potential drug toxicity (41,42).…”

Section: Discussionmentioning

confidence: 99%

“…MICs for strains with high-level resistance and double mutations were .16 mg/ml for all isolates tested. The mutations found in double rpoB mutated strains often have low RIF MICs when found alone, but studies utilizing the Bactec MGIT 960 culture system and the agar proportion method have independently reported finding higher levels of RIF resistance when more than one of these mutations is detected (42)(43)(44)(45)(46)(47). Low-level resistance mutations were found to have a much lower range of MICs, 0.25 to 1.0 mg/ml, while the MIC range of rpoB wild-type strains was #0.12 to 0.5 mg/ml.…”

Section: Discussionmentioning

confidence: 99%

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Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

et al. 2021

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Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

et al. 2021

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“…Furthermore, due to the high prevalence of MDR-TB among R-resistant cases, R resistance is considered as surrogate for MDR-TB and amongst the WHO-endorsed rapid drug susceptibility testing (DST) tools, one of the most frequently utilized tools tests only for R resistance [20–23]. However, this approach is questioned by some experts and, hence, additional DST for H, especially in low-incidence settings, is recommended [24, 25]. Here too, information on drug resistance patterns is crucial to inform the utilization of different resistance diagnostic methods.…”

Section: Introductionmentioning

confidence: 99%

First-line tuberculosis drug resistance patterns and associated risk factors in Germany, 2008-2017

et al. 2019

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Background Drug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), poses a threat to public health. While standard surveillance focuses on Rifampicin and/or Isoniazid resistance, little is known about other resistance patterns. This study aims to identify predominant drug resistance (DR) patterns in Germany and risk factors associated with them in order to inform diagnostic and treatment strategies. Methods Case-based TB surveillance data notified in Germany from 2008–2017 were utilized to investigate DR and MDR-TB patterns for Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S). Predominant patterns were further analyzed stratified by sex, age, country of birth, prior TB, and disease site. Multivariable logistic regression was conducted to determine risk factors associated with any resistance, MDR-TB, and complete HRZES resistance. Results 26,228 cases with complete DST results were included in the study, among which 3,324 cases had any DR (12.7%). Four patterns were predominant, representing about ¾ of all cases with any resistance (S: 814 [3.1%]; H: 768 [2.9%]; HS: 552 [2.1%]; Z: 412 [1.6%]). High proportions of S and H resistances were found among both German and foreign-born populations, especially those born in Eastern Europe, and were unexpectedly high among children (H: 4.3%; S: 4.6%). Foreign-born cases had significantly higher proportion of any resistance (16.0%) and MDR-TB (3.3%) compared to German-born cases (8.3% and 0.6%). Of 556 MDR-TB cases, 39.2% showed complete HRZES resistance. Logistic regression revealed having prior TB and being foreign-born as consistently strong risk factors for any DR, MDR-TB, and complete HRZES resistance. Conclusions DR patterns observed in Germany, particularly for MDR-TB were more complex than expected, highlighting the fact that detailed drug-testing results are crucial before incorporating HRZES drugs in MDR-TB treatment. Furthermore, the relatively high rate of H-resistance in Germany provides strong rationale against the use of only H-based preventive therapy for LTBI.

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“…These trend differences between RR and MDR rates are in keeping with the knowledge that the proportion of RR strains susceptible to isoniazid vary in different areas of the world, i.e. RR-TB is not always a good proxy for diagnosis of MDR-TB [1, [12][13][14]. Thus, in order to obtain a correct diagnosis of MDR-TB, detection of rifampicin resistance by rapid molecular assays (e.g.…”

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confidence: 59%

Trend in rifampicin-, multidrug- and extensively drug-resistant tuberculosis in Italy, 2009–2016

et al. 2018

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Tuberculosis (TB) caused by strains of Mycobacterium tuberculosis that are rifampicin-resistant (RR), multidrug-resistant (MDR) (strains resistant to at least isoniazid and rifampicin) or extensively drug-resistant (XDR) (MDR strains resistant to any fluoroquinolone (FQ) and to at least one second-line injectable drug (SLID): kanamycin, capreomycin or amikacin) is a major threat to TB control globally. All three groups require treatment with second-line drugs (SLDs) [1]. We previously reported that MDR-and XDR-TB in Italy occurred mostly in foreign-born persons (FBPs) [2,3], but no major information on RR, MDR or XDR trends in FBPs and Italian-born persons (IBPs) were shown. Here, we documented these trends from 2009 to 2016 (figure 1).In our country, the surveillance of drug-resistant TB is coordinated by the World Health Organization (WHO) Supranational Reference Laboratory (SRL) in Rome collaborating with the Italian Multicentre Study on Resistance to Antituberculosis Drugs (SMIRA), a laboratory network presently comprised of 42 laboratories in 18 out of 20 regions, and with the WHO SRL in Milan. In 2015, the SMIRA network, which is periodically examined by first-line drug and SLD proficiency testing exercises [2,4], covered 69.3% of nationwide notified cases [5] and contributed the majority of cases included in annual reports of European Centre for Disease Prevention and Control/WHO.In 2009-2016, a total of 15 985 M. tuberculosis strains from TB patients with known nationality (mean±SD 2004±121 strains per year) were isolated. Strains from patients with unknown nationality (n=3083) were not included in the study. Figure 1a shows that most MDR/RR strains were isolated from FBPs, and that MDR and RR (any resistance to rifampicin, whether monoresistance, polyresistance, MDR or XDR) rates in FBPs decreased in parallel with those of FBPs+IBPs. MDR rates in FBPs+IBPs decreased with a mean annual change of −3.8%, in keeping with −2.8% and −3.8% MDR-TB decline reported for the European region in 2004-2013 [6] and 2008-2012 [7], respectively. In IBPs, the RR rates decreased while MDR rates stabilised at 0.6±0.1%.Starting from 2011, the SMIRA laboratories determined SLD susceptibility, and from 2011 to 2016, reported data on 375 MDR strains isolated from 12 240 TB cases, including 300 MDR cases from 6845 FBPs and 75 MDR cases from 5395 IBPs. The trends showed that resistance of 300 FBP strains to both FQs and SLIDs (XDR strains) was stable (10.8±1.6%) (figure 1b). Despite data fluctuations, trends were quite stable also for resistance to FQs (22.6±5%) and SLIDs (27.4±4%), and for susceptibility to SLIDs+FQs (48.1±7.3%). As to the 75 IBP strains, the corresponding values were 1.9±1.6%, 4.1±3%, 5.5±2.9% and 7.6±5.3%, respectively, indicating that resistances to SLIDs and/or FQs were much lower in IBPs than in FBPs.Out of 15 985 M. tuberculosis strains examined, 7248 (45.3%) were isolated from IBPs and 8737 (54.7%) from FBPs who had arrived in Italy from 107 countries, including 65 countries with non-MDR and 42 with MDR s...

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The reliability of rifampicin resistance as a proxy for multidrug-resistant tuberculosis: a systematic review of studies from Iran

Cited by 22 publications

References 25 publications

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

First-line tuberculosis drug resistance patterns and associated risk factors in Germany, 2008-2017

Trend in rifampicin-, multidrug- and extensively drug-resistant tuberculosis in Italy, 2009–2016

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