801. Emergence of Multi-Drug Resistance Tuberculosis During the Treatment Course of Pan-Susceptible TB: A Case Series

Abstract Background Successful treatment of tuberculosis (TB) requires monitoring for clinical, radiographic, and microbiologic improvement. Even after negative cultures are obtained, there should be continued monitoring of sputa. If cultures become positive during treatment of drug susceptible TB (DS-TB), there should be concern for multi-drug-resistant tuberculosis (MDR-TB). We present two cases diagnosed with DS-TB who developed MDR-TB during treatment. Case Report: Case 1 is a 33-year-old male who was incarcerated in Peru. During incarceration in 2008, three of his cellmates had MDR-TB and he was diagnosed with DS-TB and treated with directly observed therapy (DOT) for 7 months. In Texas in 2015 he was diagnosed with DS-TB and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Five months into DOT, his sputa became culture positive with molecular detection of drug resistance (MDDR) and drug susceptibility testing (DST) revealing resistance to all of RIPE. Repeat MDDR and DST of the 2015 isolate showed no resistance. Genotyping of the two isolates were identical by mycobacterial interspersed repetitive units (MIRU) and spoligotyping. However, whole genome sequencing showed two different isolates. Case 2 is a 63-year-old female diagnosed with DS-TB in Saipan and started on RIPE in April 2017. She was on DOT until July when she moved to Texas and was lost to follow-up until September. She claims adherence with rifampin and isoniazid during this time. All sputa collected between diagnosis and September were smear and culture negative. Six months into therapy, she had sputa that was culture positive with MDDR and DST showing MDR-TB. Her isolates from Saipan and Texas were sent for genotyping. The MIRU and spoligotyping showed two different isolates. Conclusion These cases show the importance of following cultures throughout treatment. Traditionally, MDR-TB is thought to be due to poor adherence. However, in high prevalence areas, heterogeneous infection with two different strains is an important consideration for the cause of MDR-TB. Concomitant infection of DS and MDR-TB can occur with MDR-TB not being detected until far into therapy. These cases represent heterogeneous exogenous infection of DS and MDR-TB—only discovered after meticulous culture monitoring. Disclosures All authors: No reported disclosures.

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Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

Journal of Clinical Microbiology ◽

10.1128/jcm.02283-14 ◽

2014 ◽

Vol 53 (1) ◽

pp. 131-135 ◽

Cited By ~ 2

Author(s):

Limei Zhu ◽

Qiao Liu ◽

Leonardo Martinez ◽

Jinyan Shi ◽

Cheng Chen ◽

...

Keyword(s):

Drug Resistance ◽

Diagnostic Value ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Standard Drug ◽

Related Data ◽

Resistant Tuberculosis ◽

Mdr Tb ◽

Previously Treated

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.

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Anti-tuberculosis Drug Resistance Pattern among Different Category of Tuberculosis Patients

Journal of Medicine ◽

10.3329/jom.v10i2.2812 ◽

1970 ◽

Vol 10 (2) ◽

pp. 45-47 ◽

Cited By ~ 2

Author(s):

Mostafizur Rahman ◽

SM Mostafa Kamal ◽

Fazle Rabbi Mohammed ◽

Md Billal Alam ◽

HAM Nazmul Ahasan

Keyword(s):

Drug Resistance ◽

Susceptibility Testing ◽

Absolute Number ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Therapeutic Interventions ◽

Multi Drug Resistance ◽

Resistance Pattern ◽

Drug Resistance Pattern ◽

Mdr Tb

Background: Anti-Tuberculosis (TB) drug resistance is emerging as a new global health problem. No national data on drug resistance is available in Bangladesh. The absolute number of multidrug resistant TB (MDR-TB) is expected to be high considering high TB burden. This study was aimed to determine the resistance pattern of mycobacterium tuberculosis (MTB) isolates among different category of patient. Method: A total 1123 randomly selected patients having clinical and or radiological features of tuberculosis attending out patients department of NIDCH were enrolled in this study during January to December, 2008. Sputum were collected and processed for culture by digestion, decontamination and concentration following modified Petroff's method and were inoculated on to two slopes of Lowenstein- Jensen (L-J) media for six weeks. The identity of the isolates was made by growth rate, colony morphology, P-nitrobenzoic acid (PNB) susceptibility, catalase and nitrate reduction tests. Ultimately drug susceptibility testing (DST) were performed. Result: Drug susceptibility testing for Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Streptomycin (SM) was done among 363 cases. Resistance rates for INH, RIF, EMB and SM were 76.03%, 71.63%, 27.55% and 55.65% respectively. According to DST report, total 221 cases were detected as multi drug resistant TB (MDR-TB). Among them, 87% cases were MDR-TB in category II (CAT - II) failure and 13% were MDR-TB in category I (CAT - I) failure and it was 0% in new cases. Conclusion: Pattern of anti TB drug resistance was identified in this study. More surveillance and immediate therapeutic interventions should be performed in order to combat the threat of MDR-TB to the general population. Keywords: Tuberculosis, Multi drug resistance, Drug susceptibility testing. doi: 10.3329/jom.v10i2.2812 J MEDICINE 2009; 10 : 45-47

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Comparative Utility of Genetic Determinants of Drug Resistance and Phenotypic Drug Susceptibility Profiling in Predicting Clinical Outcomes in Patients With Multidrug-Resistant Mycobacterium tuberculosis

Frontiers in Public Health ◽

10.3389/fpubh.2021.663974 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yang Che ◽

Tianchi Yang ◽

Lv Lin ◽

Yue Xiao ◽

Feng Jiang ◽

...

Keyword(s):

Drug Resistance ◽

Latent Class ◽

Treatment Success ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Sputum Smear ◽

Genetic Determinants ◽

Resistant Tuberculosis ◽

Mdr Tb

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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Patterns of Drug Resistance Among Tuberculosis Patients in West and Northwestern Iran

The Open Respiratory Medicine Journal ◽

10.2174/1874306401610010029 ◽

2016 ◽

Vol 10 (1) ◽

pp. 29-35 ◽

Cited By ~ 2

Author(s):

Leyla Sahebi ◽

Khalil Ansarin ◽

Parviz Mohajeri ◽

Majid Khalili ◽

Amir Monfaredan ◽

...

Keyword(s):

Drug Resistance ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Effective Control ◽

Cross Sectional ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Mdr Tb ◽

History Of ◽

Hiv Negative

Background: Tuberculosis (TB) is the leading cause of morbidity and mortality among chronic infectious diseases. Objective: The goal of this cross-sectional study (2011-2013;2013) was to examine the patterns of TB drug resistance among HIV-negative pulmonary TB patients in regions near the Iranian border. Method: To this end, MTB isolates were harvested from 300 HIV-negative, pulmonary smear-positive TB patients from the northwest and west Iranian border provinces. Isolates were subjected to first and second-line drug susceptibility testing by the 1% proportion method. Demographic and clinical data were provided using a questionnaire and information from patient records. Results were analyzed using SPSS-18. Results: The mean age of the patients was 52.03 years and 54.3% were male. The prevalence of resistance to any TB drug was 13.6% (38 cases). Eleven percent of the new treatment TB group (28 patients) and 40.7% of the retreatment TB group (11 patients) were resistant to all TB drugs. Twelve (4.3%) patients had multidrug-resistant tuberculosis (MDR-TB) (2.38% in the new TB treatment group and 23.1% in the retreatment group). One patient had extensively drug-resistant tuberculosis (XDR-TB). There was a statistically significant relationship between TB drug resistance and smoking (p=0.02) and a history of migration from village to city (p=0.04), also between TB drug resistance and recurrence of TB in patients that had previously received treatment (p<0.001). Conclusion: Knowledge of drug resistance patterns for new and previously treated cases is critical for effective control of MDR-TB in different regions of the country. The burden of MDR-TB in retreatment cases was high. Previous TB treatment was one of the most important mokers and those who had a history of rural to urban migration were at high risk for the occurrence of TB drug resistance.

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Anti-tuberculosis drug resistance pattern among pulmonary tuberculosis patients with or without HIV infection in Mwanza, Tanzania

Tanzania Journal of Health Research ◽

10.4314/thrb.v14i4.2 ◽

2012 ◽

Vol 14 (4) ◽

Author(s):

Nyagosya Range ◽

Henrik Friis ◽

Said Mfaume ◽

Pascal Magnussen ◽

John Changalucha ◽

...

Keyword(s):

Drug Resistance ◽

Drug Susceptibility ◽

Ratio Method ◽

Multi Drug Resistance ◽

Resistance Pattern ◽

Newly Diagnosed ◽

Drug Resistance Pattern ◽

Mdr Tb ◽

Susceptibility Tests ◽

Culture Positive

Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control, particularly multi-drug resistance TB (MDR-TB). The objective of this study was to determine the prevalence of primary and acquired anti-TB drug resistance among newly diagnosed pulmonary TB (PTB) and relapse cases. Sputa were collected from newly diagnosed and relapse PTB patients. Drug susceptibility tests (DST) were performed on sputum culture positive isolates of Mycobacterium tuberculosis using resistance ratio method on four first-line anti-TB drugs: rifampicin, isoniazid, ethambutol and streptomycin. Demographic and anthropometric information was collected and HIV status was determined. Of the 523 culture positive isolates, DST results were available for 503 (96%), 455 were new and 48 were relapse cases. Resistance to at least one of the four drugs was observed in 7.8% (39/503) of the isolates, 7.3% (33/455) were new and 12.5% (6/48) were from relapse cases. Mono resistance to isoniazid was higher in both among new 45.5% (15/33) and relapse 50.0% (3/6) cases. Resistance to rifampicin and streptomycin alone was equal 4/33 (12.1%) and only among new cases. Resistance to ethambutol alone was only one among new cases. Overall MDR-TB prevalence was 2.4% (12/503), nine were new and three were relapse cases. MDR-TB was 17.9% (7/39) for rifampicin and isoniazid. Prevalence of HIV was 43.3% and was similar among new and relapse cases and not risk factor for drug resistance. Majority of PTB patients (52%) had BMI below 18 kg/m2. Those with BMI greater than 18 kg/m2 were more likely to develop drug resistance than those with BMI below 18 kg/m2 (P=0.004). With the resurgence of TB and the high prevalence of HIV among TB patients, prevalence of drug resistance is still low both among new and relapses cases. Despite the current low drug resistance, there is a need for continuous monitoring of the resistance.

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Drug Resistant Tuberculosis in the Northern Region of Zambia: A Retrospective Study

Frontiers in Tropical Diseases ◽

10.3389/fitd.2021.735028 ◽

2021 ◽

Vol 2 ◽

Author(s):

Ngula Monde ◽

Mildred Zulu ◽

Mathias Tembo ◽

Ray Handema ◽

Musso Munyeme ◽

...

Keyword(s):

Drug Resistance ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Multi Drug Resistance ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tuberculosis Patients ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis

BackgroundZambia like many countries in sub-Saharan Africa is affected with drug resistant tuberculosis. However, the drug resistant tuberculosis situation over the years has not been described in various regions of the country. Consequently, this study aims to determine the drug resistant tuberculosis burden in northern regions of Zambia over a four-year period based on data generated from a Regional Tuberculosis Reference Laboratory.MethodTwo hundred and thirty two (232) Tuberculosis Drug Susceptibility Testing results over a four-year period (2016-2019) were reviewed. Data was collected from tuberculosis registers and patient request forms and entered into a pre-tested standardized checklist and later entered in Excel Computer software. Double blinded checking was done by two independent data clerks to minimize duplication of cases. Cleaned data was then imported in R programme for analysis. Bivariant and descriptive statistics were performed and reported.ResultsOf 232 Drug Susceptibility Testing results, 90.9% were drug resistant TB while 9% were drug susceptible. Fifty three percent (53%) of these were multi-drug resistant Tuberculosis and 32% were confirmed as Rifampicin Mono-resistance. Only 1.7% of the Multi-drug resistant Tuberculosis patients were Pre-extensively drug-resistant Tuberculosis. Copperbelt province had the largest proportion (46.0%) of multi-drug resistant tuberculosis patients followed by Luapula (8.1%) and North-Western (4.7%) provinces. In new and previously treated patients, the proportion of Multi-drug resistant tuberculosis was 71.8% and 28.7% respectively. History of previous anti-tuberculosis treatment and treatment failure were associated with multi-drug resistance TB.Conclusion and RecommendationThis study has shown a small increase in the proportions of drug resistant tuberculosis cases over the four years under review with high rates being recorded on the Copperbelt Province. Previous treatment to first line TB treatment and treatment failure were associated with development of Multi-drug resistance. We therefore recommend strengthened routine laboratory surveillance and improved case management of multi-drug resistant tuberculosis patients in the region.

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Rifampin-resistant Tuberculosis in the United States, 1998–2014

Clinical Infectious Diseases ◽

10.1093/cid/ciz491 ◽

2019 ◽

Vol 70 (8) ◽

pp. 1596-1605 ◽

Cited By ~ 1

Author(s):

Lisa Sharling ◽

Suzanne M Marks ◽

Michael Goodman ◽

Terence Chorba ◽

Sundari Mase

Keyword(s):

United States ◽

Temporal Trends ◽

The United States ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Adjusted Risk ◽

Resistant Tuberculosis ◽

Rifampin Resistance ◽

Culture Positive ◽

Initial Drug

Abstract Background Monoresistance to rifamycins necessitates longer and more toxic regimens for tuberculosis (TB). We examined characteristics and mortality associated with rifampin-monoresistant (RMR) TB in the United States. Methods We analyzed Mycobacterium tuberculosis culture-positive cases reported to the National TB Surveillance System (excluding California) between 1998 and 2014. We defined RMR TB found on initial drug susceptibility testing and possible acquired rifampin-resistant (ARR) TB. We assessed temporal trends in RMR TB. For both classifications of rifampin resistance, we calculated adjusted risk ratios (adjRRs) and 95% confidence intervals (CIs) for characteristics associated with mortality when compared with drug-susceptible TB in multivariable models using backward selection. Results Of 180 329 TB cases, 126 431 (70%) were eligible for analysis, with 359 (0.28%) of eligible cases reported as RMR. The percentage of RMR TB cases with HIV declined 4% annually between 1998 and 2014. Persons with HIV and prior TB were more likely to have RMR TB (adjRR, 25.9; 95% CI, 17.6–38.1), as were persons with HIV and no prior TB (adjRR, 3.1; 95% CI, 2.4–4.1) vs those without either characteristic, controlling for other statistically significant variables. RMR cases had greater mortality (adjRR, 1.4; 95% CI, 1.04–1.8), controlling for HIV and other variables. Persons with HIV had greater risk of ARR than persons without HIV (adjRR, 9.6; 95% CI, 6.9–13.3), and ARR was also associated with increased mortality, controlling for HIV and other variables. Conclusions All forms of rifampin resistance were positively associated with HIV infection and increased mortality.

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A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay

Laboratory Medicine ◽

10.1093/labmed/lmaa016 ◽

2020 ◽

Vol 51 (6) ◽

pp. 606-613

Author(s):

Ye-Cheng Zhou ◽

Shu-Mei He ◽

Zi-Lu Wen ◽

Jun-Wei Zhao ◽

Yan-Zheng Song ◽

...

Keyword(s):

Clinical Care ◽

Pcr Amplification ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Hybridization Assay ◽

Enzyme Linked Immunosorbent Assay ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

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.

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Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0508 ◽

2020 ◽

Vol 24 (5) ◽

pp. 485-491

Author(s):

D. Butov ◽

C. Lange ◽

J. Heyckendorf ◽

I. Kalmykova ◽

T. Butova ◽

...

Keyword(s):

Treatment Outcomes ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Poor Treatment ◽

Mdr Tb ◽

Observational Cohort

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.

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Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting

Epidemiology and Infection ◽

10.1017/s0950268810002797 ◽

2010 ◽

Vol 139 (11) ◽

pp. 1784-1793 ◽

Cited By ~ 12

Author(s):

H. LIN ◽

S. SHIN ◽

J. A. BLAYA ◽

Z. ZHANG ◽

P. CEGIELSKI ◽

...

Keyword(s):

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Urban Setting ◽

South American ◽

Resistant Disease ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Incident Cases

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.

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