scholarly journals Acquired Drug Resistance During the Turnaround Time for Drug Susceptibility Testing Impacts Outcome of Tuberculosis

2021 ◽  
Author(s):  
Jiahui Zhu ◽  
Lina Davies Forsman ◽  
Ziwei Bao ◽  
Yan Xie ◽  
Zhu Ning ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcome ◽  
Acquired Resistance ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Sputum Culture ◽  
Acquired Drug Resistance ◽  
Culture Conversion

Abstract BackgroundThe impacts of acquired resistance to first-line drugs (FLDs) during turnaround time (TAT) for drug susceptibility testing (DST) are still unclear. Thus, we aimed to investigate the impacts of acquired resistance to FLDs during TAT for DST on tuberculosis (TB) standard treatment.MethodWe performed a prospective cohort study between 2013 and 2018 in China, including sputum culture-positive TB patients with a baseline DST result for a Mycobacterium tuberculosis (Mtb) isolate collected at TB diagnosis and a follow-up DST result for a Mtb isolate collected when baseline DST result became available. Mtb isolates with acquired drug resistance were identified by the comparison between baseline and follow-up DST. Treatment outcome were evaluated by sputum culture conversion and World Health Organization (WHO) treatment outcome definitions. ResultsIn total, 65 patients with Mtb isolates with acquired resistance to any FLDs and 130 patients with consistent drug susceptibility profile were included in the analysis. In a Cox proportional hazard regression analysis, acquired pyrazinamide-resistance (aHR 0.54, 95%CI: 0.36-0.81) and acquired isoniazid-resistance (aHR 0.50, 95%CI: 0.29-0.85) were associated with prolonged time to sputum culture conversion. Furthermore, independent risk factors of treatment failure included acquired INH-resistance (aOR 7.64, 95%CI: 2.39-16.08) and acquired PZA-resistance (aOR 5.71, 95%CI: 2.31-14.12).ConclusionThe association between acquisition of drug resistance and treatment outcome highlights the importance of shortening the turnaround time of DST.

scholarly journals 800. Drug-Resistant TB: An Experience From Qatar

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S287-S287
Author(s):  
Maisa Ali ◽  
Faraj Alhowady ◽  
Waqar Munir ◽  
Muna Almaslamani ◽  
Abdulatif Alkhal ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcome ◽  
Indian Subcontinent ◽  
Disease Patient ◽  
Sputum Culture ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Sputum Culture Conversion ◽  
Culture Conversion

Abstract Background Drug-resistant tuberculosis (DR-TB) is an important issue for public health. This study was conducted to evaluate the characteristics, treatment outcome, and risk factors associated with 223 DR-TB cases in the State of Qatar. Methods A descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010–March 2015. Demographic and clinical data extracted included: patient’s age, sex, and country of origin; disease site (pulmonary or extra-pulmonary); presence of comorbidities, HIV/AIDS status, previous chemoprophylaxis and/or previous treatment for TB, and anti-TB drug resistance the resistance pattern of isolated mycobacteria. The sputum culture conversion rate and treatment outcome was assessed for the patient who completed their treatment in Qatar Results Of 3,301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to one or more first-line drugs, to isoniazid in 3.1% (n = 102), streptomycin in 1.2% (n = 41), rifampicin in 0.2% (n = 6), ethambutol in 0.15% (n = 5), and multi-drug resistance in 1.2% (n = 38) of patients. Among the resistant TB patients, more common demographic characteristics were former resident of Indian subcontinent (64.1%). A history of anti-TB treatment was not a risk factor with drug resistance in our cohort. Only 111 (49.7%) patients were tested for HIV antibodies and the results were all negative. There was significant correlation between the type of drug-resistance and CXR finding (23.3% had cavity—P = 0.019). Sputum culture conversion to negative at 2 month of therapy was 94% (n = 101), whereas 122 cases lost follow-up. The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment, show cure rate of 97.6%, and relapse of 2.4%. However, 137 cases (61.4% from total) they left the country before completion of therapy. Conclusion Drug-resistant TB in Qatar is influenced by migration, especially from the Indian subcontinent, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control. Disclosures All authors: No reported disclosures.

Clinical interpretation of drug susceptibility tests in tuberculosis

2020 ◽  
Vol 16 ◽  
Author(s):  
Rafael Laniado-Laborín
Keyword(s):  
Drug Resistance ◽  
Drug Regimen ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Therapeutic Decisions ◽  
Mdr Tb ◽  
Frequent Mutations ◽  
Susceptibility Tests

: Prompt and accurate diagnosis of drug resistance is essential for optimal treatment of drug-resistant tuberculosis. However, only 20% of the more than half a million patients eligible for the treatment of MDR-TB/RR-TB receive an appropriate drug regimen. Drug-resistant TB regimens must include a sufficient number of effective medications, a significant challenge for clinicians worldwide, as most are forced to make therapeutic decisions without any, or very little information on drug susceptibility testing. Although phenotypic DST is still commonly regarded as the gold standard for determining M. tuberculosis susceptibility to antituberculosis drugs, it has several limitations, mainly its prolonged turnaround time. Molecular methods based on M. tuberculosis genomic DNA sequencing have been developed during the past two decades, to identify the most common mutations involved in drug resistance. The Xpert®MTB/RIF is a real-time polymerase chain reaction that offers results in less than two hours and has an overall sensitivity for rifampin resistance of 96% and 98% specificity. Line probe assays (LPAs) are commercial DNA strip-based tests for detecting the most frequent mutations responsible for resistance to rifampin, isoniazid, fluoroquinolones, and second-line injectable drugs. Discrepancies between phenotypic and genotyping methods are a problem that the clinician will face in everyday practice. However, any resistance result (with any type of test) in a person with risk factors for harboring resistant microorganisms should be considered initially resistant while the results of complementary tests are available.

scholarly journals Clinical Outcomes among Patients with Drug-resistant Tuberculosis receiving Bedaquiline or Delamanid Containing Regimens

2019 ◽  
Author(s):  
R R Kempker ◽  
L Mikiashvili ◽  
Y Zhao ◽  
D Benkeser ◽  
K Barbakadze ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcomes ◽  
Previous Treatment ◽  
Sputum Culture ◽  
Acquired Drug Resistance ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion

Abstract Background Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR TB); however, there is limited data guiding their use and no comparison studies. Methods We conducted a prospective observational study among patients with MDR TB in Georgia receiving a bedaquiline or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation (TMLE) and superlearning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen. Results Among 156 patients with MDR TB, 100 were enrolled and 95 were receiving a bedaquiline (n=64) or delamanid (n=31) based regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine and a fluoroquinolone. Median effective drugs received among patients on bedaquiline (4, IQR 4-4) and delamanid (4, IQR 3.5-5) based regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs. 10%, p <0.01). Adjusted rates of sputum culture conversion at two months (67 vs. 47%, p=0.10) and six months (95 vs. 74%, p<0.01) and favorable clinical outcomes (96 vs. 72%, p<0.01) were higher among patients receiving bedaquiline versus delamanid. Conclusions Among patients with MDR TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion and favorable outcomes and a lower rate of acquired drug resistance versus delamanid-based regimens.

scholarly journals The Use of a Shared Services Model for Mycobacteriology Testing: Lessons Learned

2017 ◽  
Vol 133 (1) ◽  
pp. 93-99
Author(s):  
Cortney Stafford ◽  
Robyn Atkinson-Dunn ◽  
Sarah N. Buss ◽  
Tracy Dalton ◽  
Debbie Gibson ◽  
...  
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Molecular Detection ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Health Concern ◽  
Resistance Testing ◽  
Shared Services

Objectives: Public health laboratories (PHLs) provide essential services in the diagnosis and surveillance of diseases of public health concern, such as tuberculosis. Maintaining access to high-quality laboratory testing is critical to continued disease detection and decline of tuberculosis cases in the United States. We investigated the practical experience of sharing tuberculosis testing services between PHLs through the Shared Services Project. Methods: The Shared Services Project was a 9-month-long project funded through the Association of Public Health Laboratories and the Centers for Disease Control and Prevention during 2012-2013 as a one-time funding opportunity to consortiums of PHLs that proposed collaborative approaches to sharing tuberculosis laboratory services. Submitting PHLs maintained testing while simultaneously sending specimens to reference laboratories to compare turnaround times. Results: During the 9-month project period, 107 Mycobacterium tuberculosis complex submissions for growth-based drug susceptibility testing and molecular detection of drug resistance testing occurred among the 3 consortiums. The median transit time for all submissions was 1.0 day. Overall, median drug susceptibility testing turnaround time (date of receipt in submitting laboratory to result) for parallel testing performed in house by submitting laboratories was 31.0 days; it was 43.0 days for reference laboratories. The median turnaround time for molecular detection of drug resistance results was 1.0 day (mean = 2.8; range, 0-14) from specimen receipt at the reference laboratories. Conclusions: The shared services model holds promise for specialized tuberculosis testing. Sharing of services requires a balance among quality, timeliness, efficiency, communication, and fiscal costs.

scholarly journals Drug Susceptibility Testing Guided Treatment for Drug-Resistant Spinal Tuberculosis: A Retrospective Analysis of 19 Patients

2013 ◽  
Vol 98 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Lan Xu ◽  
Xu Jian-Zhong ◽  
Liu Xue-Mei ◽  
Ge Bao-Feng
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Extrapulmonary Tuberculosis ◽  
Spinal Tuberculosis ◽  
Previous History ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Acquired Drug Resistance ◽  
Mdr Tb

Abstract Spinal tuberculosis is the most common manifestation of extrapulmonary tuberculosis. However, there have been few reports on the topic of drug-resistant spinal tuberculosis. The aim of this study was to investigate the efficacy and safety of treatment with a combination of surgery and individual chemotherapy guided by drug susceptibility testing for drug-resistant spinal tuberculosis. We retrospectively analyzed 19 patients with drug-resistant spinal tuberculosis. After surgery, individual chemotherapy was tailored for each patient according to his or her drug resistance profile and previous history of chemotherapy. The patients were followed up clinically and radiologically for an average period of 36 months. Among 19 drug-resistant spinal tuberculosis cases, 16 were multidrug-resistant tuberculosis (MDR-TB), and 3 were non–MDR-TB. The patients with MDR-TB and non–MDR-TB had undergone previous chemotherapy for an average of 12.50 ± 2.00 months (0–55 months) and 5.50 ± 1.20 months (0–60 months), respectively. A total of 16 patients underwent open operations, and the other 3 had percutaneous drainage and local chemotherapy. Patients received individual chemotherapy for an average of 24 months postoperatively. All patients had been cured at the final follow-up. Drug-resistant spinal tuberculosis is mainly acquired through previous irregular chemotherapy and the spread of drug-resistant strains. Treatment with a combination of surgery and individual chemotherapy is feasible in the treatment of severe complications and the prevention of acquired drug resistance.

scholarly journals Comparison of the Performances of Two In-House Rapid Methods for Antitubercular Drug Susceptibility Testing

2008 ◽  
Vol 53 (2) ◽  
pp. 808-810 ◽  
Author(s):  
Agustina I. de la Iglesia ◽  
Emma J. Stella ◽  
Héctor R. Morbidoni
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Sensitivity And Specificity ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Antitubercular Drug ◽  
Rapid Methods ◽  
Resistance Assessment

ABSTRACT Resistance to rifampin (rifampicin), isoniazid, and streptomycin of 69 Mycobacterium tuberculosis isolates was analyzed by an in-house method based on mycobacteriophage D29 and a colorimetric micromethod. Both methods showed sensitivity and specificity values ranging from 93% to 100%. These simple methods offer an option for drug resistance assessment of M. tuberculosis.

scholarly journals A histone methyltransferase inhibitor can reverse epigenetically acquired drug resistance in the malaria parasite Plasmodium falciparum

2019 ◽  
Author(s):  
Amanda Chan ◽  
Alexis Dziedziech ◽  
Laura A Kirkman ◽  
Kirk W Deitsch ◽  
Johan Ankarklev
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Acquired Resistance ◽  
Anion Channel ◽  
Histone Methyltransferase ◽  
Drug Uptake ◽  
Natural Setting ◽  
Membrane Expression ◽  
Acquired Drug Resistance ◽  
Histone Modifiers

AbstractMalaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum.ImportanceDrug resistance is a major concern for the treatment of infectious diseases throughout the world. For malaria, a novel mechanism of resistance was recently described in which epigenetic modifications led to a resistance phenotype that is rapidly reversible, thus reducing the fitness cost that is often associated with genetic mutations that lead to resistance. The possibility of this type of resistance arising in a natural setting is particularly troubling since parasites could rapidly switch to and from a resistant phenotype, thus making it especially difficult to combat. Here we show that application of a histone methyltransferase inhibitor can rapidly reverse the epigenetic changes that lead to drug resistance, thereby causing parasites to revert to a drug sensitive phenotype. This is a novel application of drugs that target epigenetic modifiers and lends additional support for ongoing efforts to develop drugs against malaria that target the histone modifiers of the parasite.

scholarly journals Genetic Identification and Drug-Resistance Characterization of Mycobacterium tuberculosis Using a Portable Sequencing Device. A Pilot Study

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 548 ◽  
Author(s):  
Jorge Cervantes ◽  
Noemí Yokobori ◽  
Bo-Young Hong
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Genetic Identification ◽  
Sequencing Analysis ◽  
Antimicrobial Resistance Genes ◽  
Long Read ◽  
Drug Resistance Prediction ◽  
Almost All

Clinical management of tuberculosis (TB) in endemic areas is often challenged by a lack of resources including laboratories for Mycobacterium tuberculosis (Mtb) culture. Traditional phenotypic drug susceptibility testing for Mtb is costly and time consuming, while PCR-based methods are limited to selected target loci. We herein utilized a portable, USB-powered, long-read sequencing instrument (MinION), to investigate Mtb genomic DNA from clinical isolates to determine the presence of anti-TB drug-resistance conferring mutations. Data analysis platform EPI2ME and antibiotic-resistance analysis using the real time ARMA workflow, identified Mtb species as well as extensive resistance gene profiles. The approach was highly sensitive, being able to detect almost all described drug resistance conferring mutations based on previous whole genome sequencing analysis. Our findings are supportive of the practical use of this system as a suitable method for the detection of antimicrobial resistance genes, and effective in providing Mtb genomic information. Future improvements in the error rate through statistical analysis, drug resistance prediction algorithms and reference databases would make this a platform suited for the clinical setting. The small size, relatively inexpensive cost of the device, as well as its rapid and simple library preparation protocol and analysis, make it an attractive option for settings with limited laboratory infrastructure.

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