scholarly journals Retrospective Analysis of False-Positive and Disputed Rifampin Resistance Xpert MTB/RIF Assay Results in Clinical Samples from a Referral Hospital in Hunan, China

2019 ◽  
Vol 57 (4) ◽  
Author(s):  
Peilei Hu ◽  
Hongtai Zhang ◽  
Joy Fleming ◽  
Guofeng Zhu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
False Positive ◽  
Culture System ◽  
Clinical Samples ◽  
Content Type ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Rifampin Resistance ◽  
Mgit Culture ◽  
Xpert Assay

ABSTRACT Concerns about the specificity of the Xpert MTB/RIF (Xpert) assay have arisen, as false-positive errors in the determination of Mycobacterium tuberculosis complex (MTBC) infection and rifampin (RIF) resistance in clinical practice have been reported. Here, we investigated 33 cases where patients were determined to be RIF susceptible using the Bactec MGIT 960 (MGIT) culture system but RIF resistant using the Xpert assay. Isolates from two of these patients were found not to have any mutations in the rifampin resistance determining region (RRDR) region of rpoB and had good treatment outcomes with first-line antituberculosis (anti-TB) drugs. The remaining 31 patients included 5 new cases and 26 previously treated patients. A large number of well-documented disputed mutations, including Leu511Pro, Asp516Tyr, His526Asn, His526Leu, His526Cys, and Leu533Pro, were detected, and mutations, including a 508 to 509 deletion and His526Gly, were described here as disputed mutations for the first time. Twenty-one (81%) of the 26 previously treated patients had poor treatment outcomes, and isolates from 19 (90%) of these 21 patients were resistant to isoniazid (INH) as determined using the MGIT culture system. Twenty-seven of the 31 isolates with disputed rpoB mutations were phenotypically resistant to INH, 21 (78%) being predicted by GenoType MTBDRplus to have a high level of INH resistance. Most (77.4%) of the isolates with disputed mutations were of the Beijing lineage. These findings have implications for the interpretation of false-positive and disputed rifampin resistance Xpert MTB/RIF results in clinical samples and provide guidance on how clinicians should manage patients carrying isolates with disputed rpoB mutations.

scholarly journals Discordance between Xpert MTB/RIF Assay and Bactec MGIT 960 Culture System for Detection of Rifampin-Resistant Mycobacterium tuberculosis Isolates in a Country with a Low Tuberculosis (TB) Incidence

2015 ◽  
Vol 53 (4) ◽  
pp. 1351-1354 ◽  
Author(s):  
Eiman Mokaddas ◽  
Suhail Ahmad ◽  
Hanaa S. Eldeen ◽  
Noura Al-Mutairi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Culture System ◽  
Content Type ◽  
Rifampin Resistance ◽  
Xpert Assay

Among 452 samples that were positive by the Xpert MTB/RIF (Xpert) assay and MGIT 960 system (MGIT), 440 and 10Mycobacterium tuberculosissamples were detected as rifampin susceptible and rifampin resistant, respectively. Two isolates that were rifampin susceptible by the MGIT system were rifampin resistant by the Xpert assay.rpoBsequencing identified a silent (CTG521TTG) mutation in one isolate and a missense (GAC516TAC) mutation in another. The detection of rifampin resistance is imperfect with both the Xpert assay and MGIT system. Any discordant rifampin resistance results should be confirmed by sequencing of therpoBgene.

scholarly journals Comparison of first-line tuberculosis treatment outcomes between previously treated and new patients: a retrospective study in Machakos subcounty, Kenya

2020 ◽  
Author(s):  
Johannes Ndambuki ◽  
Joseph Nzomo ◽  
Lucy Muregi ◽  
Chris Mutuku ◽  
Francis Makokha ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Outcomes ◽  
Adverse Outcome ◽  
Previous Treatment ◽  
First Line ◽  
Adherence Support ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Lost To Follow Up

Abstract Background Since 2016, patients with rifampicin-susceptible tuberculosis (TB) have been treated with the 6-month first-line regimen, regardless of treatment history. We assessed treatment outcomes of previously treated and new patients in Machakos subcounty, Kenya. Methods We performed a retrospective cohort study in patients started on first-line treatment between 2016 and 2017. Firth's logistic regression was used to estimate the effect of previous treatment on having a programmatic adverse outcome (either lost to follow-up, death, failure) and treatment failure vs treatment success (either cure or completion). Results Of 1024 new and 79 previously treated patients, 88.1% and 74.7% were treated successfully, 6.5% and 7.6% died, 4.2% and 10.1% were lost to follow-up and 1.2% and 7.6% had treatment failure, respectively. Previous treatment predicted having a programmatic adverse outcome (adjusted odds ratio [aOR] 2.4 [95% confidence interval {CI} 1.4 to 4.2]) and treatment failure (aOR 7.3 [95% CI 2.6 to 20.4]) but not mortality. Similar correlations were found in 334 new and previously treated patients with confirmed baseline rifampicin susceptibility. Conclusion Previously treated patients were more at risk of experiencing a poor treatment outcome, mainly lost to follow-up and treatment failure. Adherence support may reduce lost to follow-up. Rifampicin drug susceptibility testing coverage should increase. More robust retreatment regimens may reduce treatment failure.

scholarly journals False-positive Xpert® MTB/RIF assays in previously treated patients: need for caution in interpreting results

2014 ◽  
Vol 18 (7) ◽  
pp. 876-878 ◽  
Author(s):  
T. H. Boyles ◽  
J. Hughes ◽  
V. Cox ◽  
R. Burton ◽  
G. Meintjes ◽  
...  
Keyword(s):  
False Positive ◽  
Previously Treated Patients ◽  
Previously Treated

scholarly journals Emergence of Resistance to Macrolides and Rifampin in Clinical Isolates ofRhodococcus equifrom Foals in Central Kentucky, 1995 to 2017

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Laura Huber ◽  
Steeve Giguère ◽  
Nathan M. Slovis ◽  
Craig N. Carter ◽  
Bonnie S. Barr ◽  
...  
Keyword(s):  
Considerable Increase ◽  
Soft Tissues ◽  
Susceptibility Testing ◽  
Animal Health ◽  
Clinical Samples ◽  
Erythromycin Resistance ◽  
Content Type ◽  
Rifampin Resistance ◽  
Emergence Of Resistance

ABSTRACTThe objective of this study was to determine the prevalence ofRhodococcus equistrains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if theR. equibacterium was cultured and tested forin vitrosusceptibility to erythromycin or rifampin.In vitrosusceptibility testing to erythromycin was available for 2,169 isolates ofR. equi, while susceptibility testing to both erythromycin and rifampin was available for 1,681 isolates. Rifampin resistance was first detected in 2000, and erythromycin resistance was first detected in 2004. Between 1995 and 2006, the proportion of resistant isolates ofR. equiwas 0.7% for erythromycin and 2.3% for rifampin. There was a significant (P< 0.001) increase in the proportion of resistantR. equibetween 2007 and 2017, with 13.6% of isolates being resistant to erythromycin and 16.1% being resistant to rifampin. Between 2007 and 2017, isolates ofR. equiresistant to erythromycin or rifampin were significantly less likely to be isolated from feces than from the respiratory tract, other soft tissues, or musculoskeletal infections. The considerable increase in the prevalence of isolates ofR. equiresistant to macrolides and rifampin since 2007 is of concern for both human and animal health.

scholarly journals Genetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis in Mongolia

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Erdenegerel Narmandakh ◽  
Oyuntuya Tumenbayar ◽  
Tsetsegtuya Borolzoi ◽  
Baasansuren Erkhembayar ◽  
Tsolmon Boldoo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genetic Mutations ◽  
Isoniazid Resistance ◽  
Prevalence Survey ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Previously Treated ◽  
Resistant Strains ◽  
Rifampin Resistance

ABSTRACT Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al. analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations (B. Buyankhishig, T. Oyuntuya, B. Tserelmaa, J. Sarantuya, et al., Int J Mycobacteriol 1:40–44, 2012, https://doi.org/10.1016/j.ijmyco.2012.01.007). The GenoType MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType MTBDRplus assay, 127 (31.1%) were resistant to rifampin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and 2 (0.5%) had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 strains with any inhA mutation, 290 (98.0%) had a C15T mutation. The proportions of isoniazid-resistant strains with katG mutations were 25.3% among new cases and 36.2% among retreatment cases (P = 0.03) and 17.0% among rifampin-susceptible strains and 52.8% among rifampin-resistant strains (P < 0.01). Rifampin resistance was significantly associated with the katG mutation (adjusted odds ratio, 5.36; 95% confidence interval [CI], 3.3 to 8.67, P < 0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than in those from new cases, and the proportion in cases with rifampin resistance was higher than in cases without rifampin resistance.

A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

1997 ◽  
Vol 78 (05) ◽  
pp. 1352-1356 ◽  
Author(s):  
Emel Aygören-Pürsün ◽  
Inge Scharrer ◽  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Parvovirus B19 ◽  
Subjective Evaluation ◽  
Recombinant Factor Viii ◽  
Fviii Inhibitor ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes ◽  
Recombinant Fviii

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

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