scholarly journals Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa

Author(s):  
Zubeida Salaam-Dreyer ◽  
Elizabeth M. Streicher ◽  
Frederick A. Sirgel ◽  
Fabrizio Menardo ◽  
Sonia Borrell ◽  
...  

Rifampicin mono-resistant TB (RMR-TB, rifampicin resistance and isoniazid susceptibility) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 μg/ml (range 0.125-1 μg/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.

2021 ◽  
Author(s):  
Zubeida Salaam-Dreyer ◽  
Elizabeth M Streicher ◽  
Frederick A Sirgel ◽  
Fabrizio Menardo ◽  
Sonia Borrell Farnov ◽  
...  

Rifampicin mono-resistant TB (RMR-TB) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.01). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.01). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 ug/ml (range 0.125-1 ug/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.


Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1422
Author(s):  
Mohammad Khaja Mafij Uddin ◽  
Md. Fahim Ather ◽  
Rumana Nasrin ◽  
Tanjina Rahman ◽  
A. S. M. Iftekhairul Islam ◽  
...  

Fluoroquinolone (FQ) compounds—moxifloxacin (MOX), levofloxacin (LEV), and ofloxacin (OFL)—are used to treat multidrug-resistant tuberculosis (MDR-TB) globally. In this study, we investigated the correlation of gyr mutations among Mtb isolates with the MICs of MOX, LEV, and OFL in Bangladesh. A total of 50 MDR-TB isolates with gyr mutations, detected by the GenoType MTBDRsl assay, were subjected to drug susceptibility testing to determine the MICs of the FQs. Spoligotyping was performed to correlate the genetic diversity of the gyr mutant isolates with different MIC distributions. Among the 50 isolates, 44 (88%) had mutations in the gyrA gene, one (2%) had a mutation in the gyrB gene, and five (10%) isolates had unidentified mutations. The substitutions in the gyrA region were at A90V (n = 19, 38%), D94G (n = 16, 32%), D94A (n = 4, 8%), D94N/D94Y (n = 4, 8%), and S91P (n = 1, 2%), compared to the gyrB gene at N538D (n = 1.2%). D94G mutations showed the highest MICs for MOX, LEV, and OFL, ranging between 4.0 and 8.0 μg/mL, 4.0 and 16.0 μg/mL, and 16.0 and 32.0 μg/mL, respectively; while the most common substitution of A90V showed the lowest ranges of MICs (1.0–4.0 μg/mL, 2.0–8.0 μg/mL, and 4.0–32.0 μg/mL, respectively). Spoligotyping lineages demonstrated no significant differences regarding the prevalence of different gyr mutations. In conclusion, the substitutions of codon A90V and D94G in the gyr genes were mostly responsible for the FQs’ resistance among Mtb isolates in Bangladesh. Low levels of resistance were associated with the substitutions of A90V, while the D94G substitutions were associated with a high level of resistance to all FQs.


2020 ◽  
Vol 51 (6) ◽  
pp. 606-613
Author(s):  
Ye-Cheng Zhou ◽  
Shu-Mei He ◽  
Zi-Lu Wen ◽  
Jun-Wei Zhao ◽  
Yan-Zheng Song ◽  
...  

Abstract Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.


2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.


2010 ◽  
Vol 139 (11) ◽  
pp. 1784-1793 ◽  
Author(s):  
H. LIN ◽  
S. SHIN ◽  
J. A. BLAYA ◽  
Z. ZHANG ◽  
P. CEGIELSKI ◽  
...  

SUMMARYWe examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005–2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11 711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.


2014 ◽  
Vol 53 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Limei Zhu ◽  
Qiao Liu ◽  
Leonardo Martinez ◽  
Jinyan Shi ◽  
Cheng Chen ◽  
...  

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Marie Demers ◽  
◽  
Soyeon Kim ◽  
Sara McCallum ◽  
Kathleen Eisenach ◽  
...  

Abstract Background Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.


2020 ◽  
Author(s):  
Yuanhong Xu ◽  
Qingfeng Li ◽  
Ma Zhu ◽  
Xueqi Wu ◽  
Dongmei Wang ◽  
...  

Abstract Background: The aim of this study was to investigate the epidemiological characteristics and profile of drug-resistant tuberculosis (DR-TB) among children with TB in Sichuan province of China.Methods: From January 2015 to December 2018, microbiological culture-confirmed child TB cases (aged<15 years old) were enrolled retrospectively. Epidemiological and clinical information from these cases, and the drug susceptibility testing (DST) results of the isolates were collected and analyzed.Results: Of 317 culture-confirmed child TB cases, 16.7% (53/317) were aged under 5 years old. 54.9% were Tibetans, and 31.9% had clear history of contact with TB patients. More than half (53.9%) weren’t vaccinated by Calmette–Guérin bacillus (BCG). 30% (n=95) were diagnosed as severe TB, and 92.4% (n=293) were new cases. The ratio of severe TB in BCG vaccinated group was significant lower than that observed in unvaccinated group (p<0.01). Significantly higher proportion of severe TB among Tibetans than Han child TB cases was observed in BCG unvaccinated group (p<0.01). The overall rate of DR-TB in this study was 24.3% (77/317) and 17 multidrug-resistant tuberculosis (MDR-TB) cases were identified with rate of MDR-TB at 5.4% (17/317). No XDR case was found. 13 out of 17 MDR-TB cases (76.4%) were Tibetan children. The ratio of any resistance to four first-line drugs identified were: INH, 15.5%; RIF, 9.1%; EMB, 0.6% and SM, 6.0%, respectively. More than half of MDR patterns were resistant to INH+RIF (9/17), followed by at least resistance to INH+RIF+SM (n=7). Conclusions: This was the first investigation on the epidemiological characteristics and profiles of DR-TB among child TB cases in Southwest of China. Our findings indicated a potentially high risk of TB infection to Tibetan children in the concentrated Tibetan communities of Sichuan.


Author(s):  
Sarah Rahmayani Siregar

Tuberkulosis adalah penyakit infeksi kronis menular yang masih merupakan masalah kesehatan masyarakat di dunia termasuk Indonesia. Tuberkulosis (TB) sebagian besar akan mengalami penyembuhan dengan pengobatan. Namun tidak semua penyakit TB sembuh dengan pengobatan. Hal ini disebabkan pengobatan dari TB yang belum terlaksana dengan baik sehingga dapat pula menyebabkan terjadinya resistensi terhadap Obat Anti Tuberkulosis (OAT), berupa Multidrug Resistant Tuberkulosis (MDR TB) dan Extensively Drug Resistant Tuberculosis (XDR TB). XDR TB adalah TB yang disebabkan oleh strain yang resistensi terhadap isoniazid dan rifampisin, disertai resisten terhadap salah satu fluorokuinolon dan salah satu dari tiga obat injeksi lini kedua (amikasin, kapreomisin atau kanamisin). XDR TB diperkenalkan tahun 2006 ketika terjadi epidemi yang sangat fatal di Afrika Selatan. XDR-TB dapat ditularkan melalui bakteri yang disebarkan oleh orang yang sudah terkena resistensi obat. Diagnosis XDR-TB ditegakkan dengan uji sensitiviti obat atau Drug Susceptibility Testing (DST), bukan sekedar berdasarkan gambaran foto toraks dan adanya faktor resiko yang ada pada seseorang. WHO telah merancang strategi Directly Observed Treatment Short Course (DOTS-Plus) untuk mengelola TB M/XDR di negara-negara miskin sumber daya. Revisi National Tuberculosis Programme (RNTCP) di bawah DOTS-Plus akan menggunakan rejimen pengobatan standar (STR) kategori IV, yang terdiri dari 6 obat (kanamisin, levofloxacin, etionamid, sikloserin, pirazinamid, dan etambutol) selama 6-9 bulan fase intensif dan 4 obat (levofloxacin, ethionamide, cycloserine, dan ethambutol) selama 18 bulan dari fase lanjutan. Penyembuhan tergantung pada tingkat resistensi obat, tingkat keparahan penyakit dan apakah sistem kekebalan pasien terganggu.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Che ◽  
Tianchi Yang ◽  
Lv Lin ◽  
Yue Xiao ◽  
Feng Jiang ◽  
...  

Setting: Programmatic management of drug-resistant tuberculosis in Ningbo, China.Objective: To assess whether data-driven genetic determinants of drug resistance patterns could outperform phenotypic drug susceptibility testing in predicting clinical meaningful outcomes among patients with multidrug-resistant tuberculosis (MDR-TB).Design: We conducted a prospective cohort study of 104 MDR-TB patients. All MDR-TB isolates underwent drug susceptibility testing and genotyping for mutations that could cause drug resistance. Study outcomes were time to sputum smear conversion and probability of treatment success, as well as time to culture conversion within 6 months. Data were analyzed using latent class analysis, Kaplan–Meier curves, and Cox regression models.Results: We report that latent class analysis of data identified two latent classes that predicted sputum smear conversion with P = 0.001 and area under receiver-operating characteristic curve of 0.73. The predicted latent class memberships were associated with superior capability in predicting sputum culture conversion at 6 months and overall treatment success compared to phenotypic drug susceptibility profiling using boosted logistic regression models.Conclusion: These results suggest that genetic determinants of drug resistance in combination with phenotypic drug-resistant tests could serve as useful biomarkers in predicting treatment prognosis in MDR-TB.


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