scholarly journals Drivers and Trajectories of Resistance to New First-Line Drug Regimens for Tuberculosis

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Sourya Shrestha ◽  
Gwenan M. Knight ◽  
Mariam Fofana ◽  
Ted Cohen ◽  
Richard G. White ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Success ◽  
Drug Regimen ◽  
Transmission Model ◽  
Drug Resistant ◽  
Success Rates ◽  
First Line ◽  
New Drug ◽  
Drug Regimens ◽  
Line Drug

Abstract Background.  New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. Methods.  We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. Results.  Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated. Conclusions.  Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB.

scholarly journals Risk Factors and Treatment Outcome Analysis Associated with Second-Line Drug-Resistant Tuberculosis

2021 ◽  
Vol 2 (1) ◽  
pp. 1-12
Author(s):  
Muralidhar Aaina ◽  
Kaliyaperumal Venkatesh ◽  
Brammacharry Usharani ◽  
Muthukumar Anbazhagi ◽  
Gerard Rakesh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Drug Resistance ◽  
Drug Resistant ◽  
First Line ◽  
Drug Resistant Tuberculosis ◽  
Factors Associated ◽  
Resistant Tuberculosis ◽  
Increased Risk ◽  
Mdr Tb ◽  
Line Drug

The present study aimed at analyzing the treatment outcomes and risk factors associated with fluoroquinolone drug resistance having mutations in the gyrA and gyrB genes. A total of 258 pulmonary tuberculosis samples with first-line drug-resistant (H, R, or HR) were subjected to GenoType MTBDRsl assay for the molecular detection of mutations. Among the 258 samples, 251 were drug-resistant tuberculosis and seven were sensitive to all first-line TB drugs. Out of 251 DR-TB cases, 42 cases were MDR TB, 200 were INH mono-resistant and nine cases were RIF mono-resistant tuberculosis. Out of 251 DR-TB cases performed with a MTBDRsl assay, 14 had Pre-XDR-FQ, one patient had pre-XDR-SLID, one had extensively drug-resistant tuberculosis (XDR-TB) and 235 cases were sensitive to both FQ and SLID drugs. The study group had a mean average of 42.7 ± 16.4 years. The overall successful treatment outcomes among the MDR, INH mono-resistant, and pre-XRD patients were 70.6%, 82.0%, and 51%, respectively. The percentage of risk for the unfavorable outcomes in the pre-XDR, INH -mono-resistant, and XDR cases were 113.84% increased risk with RR 2.14; 95% CI 0.7821–5.8468. The independent risk factor associated with the unfavorable outcomes to failure was 77.78% increased risk with RR 1.78; 95% CI 0.3375–9.3655. Logistic regression analysis revealed that the percentage relative risk among MDR-TB patients for gender, male (RR: 1.85), age ≥ 61 years (RR: 1.96), and diabetics (RR: 1.05) were 84.62%, 95.83%, and 4.76%, respectively. The independent risk factors associated with INH mono-resistant cases of age 16–60 (RR: 1.86), ≥61 year (RR: 1.18), and treated cases (RR: 5.06). This study presaged the significant risk of INH mono-resistant, pre-XDR, and MDR among males, young adults, diabetics, and patients with previous treatment failure. Timely identification of high-risk patients will give pronounced advantages to control drug resistance tuberculosis diseases.

scholarly journals Cost comparison of nine-month treatment regimens with 20-month standardized care for the treatment of rifampicin-resistant/multi-drug resistant tuberculosis in Nigeria

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0241065
Author(s):  
Florence O. Bada ◽  
Nick Blok ◽  
Evaezi Okpokoro ◽  
Saswata Dutt ◽  
Christopher Akolo ◽  
...  
Keyword(s):  
Treatment Regimen ◽  
Treatment Success ◽  
Cost Savings ◽  
Drug Resistant ◽  
Second Line ◽  
Success Rates ◽  
Drug Resistant Tuberculosis ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background Globally, drug resistant tuberculosis (DR-TB) continues to be a public health threat. Nigeria, which accounts for a significant proportion of the global burden of rifampicin/multi-drug resistant-TB (RR/MDR-TB) had a funding gap of $168 million dollars for TB treatment in 2018. Since 2010, Nigeria has utilized five different models of care for RR/MDR-TB (Models A-E); Models A, B and C based on a standardized WHO-approved treatment regimen of 20–24 months, were phased out between 2015 and 2019 and replaced by Models D and E. Model D is a fully ambulatory model of 9–12 months during which a shorter treatment regimen including a second-line injectable agent is utilized. Model E is identical to Model D but has patients hospitalized for the first four months of care while Model F which is to be introduced in 2020, is a fully ambulatory, oral bedaquiline-containing shorter treatment regimen of 9–12 months. Treatment models for RR/MDR-TB of 20–24 months duration have had treatment success rates of 52–66% while shorter treatment regimens have reported success rates of 85% and above. In addition, replacing the second-line injectable agent in a shorter treatment regimen with bedaquiline has been found to further improve treatment success in patients with fluoroquinolone-susceptible RR/MDR-TB. Reliable cost data for RR/MDR-TB care are limited, specifically costs of models that utilize shorter treatment regimens and which are vital to guide Nigeria through the provision of RR/MDR-TB care at scale. We therefore conducted a cost analysis of shorter treatment regimens in use and to be used in Nigeria (Models D, E and F) and compared them to three models of longer duration utilized previously in Nigeria (Models A, B and C) to identify any changes in cost from transitioning from Models A-C to Models D-F and opportunities for cost savings. Methods We obtained costs for TB diagnostic and monitoring tests, in-patient and out-patient care from a previous study, inflated these costs to 2019 NGN and then converted to 2020 USD. We obtained other costs from the average of six health facilities and drug costs from the global drug facility. We modeled treatment on strict adherence to two Nigerian National guidelines for programmatic and clinical management of drug-resistant tuberculosis. Results We estimated that the total costs of care from the health sector perspective for Models D, E and F were $4,334, $7,705 and $3,420 respectively. This is significantly lower than the costs of Models A, B and C which were $14,781, $12, 113, $7,572 respectively. Conclusion Replacing Models A–C with Models D and E reduced the costs of RR/MDR-TB care in Nigeria by approximately $5,470 (48%) per patient treated and transitioning from Models D and E to Model F would result in further cost savings of $914 to $4,285 (21 to 56%) for every patient placed on Model F. If the improved outcomes of patients managed using bedaquiline-containing shorter treatment regimens in other countries can be attained in Nigeria, Model F would be the recommended model for the scale up of RR/MDR-TB care in Nigeria.

scholarly journals A Molecular Approach to Identification and Profiling of First-Line-Drug-Resistant Mycobacteria from Sputum of Pulmonary Tuberculosis Patients: Table 1

2012 ◽  
Vol 50 (6) ◽  
pp. 2082-2084 ◽  
Author(s):  
Imran Hussain Chowdhury ◽  
Aditi Sen ◽  
Bojlul Bahar ◽  
Avijit Hazra ◽  
Urmita Chakraborty ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Drug Resistant ◽  
Molecular Approach ◽  
First Line ◽  
Tuberculosis Patients ◽  
Line Drug

Drug-resistant genital tuberculosis of the penis in a human immunodeficiency virus non-reactive individual

2007 ◽  
Vol 56 (5) ◽  
pp. 694-695 ◽  
Author(s):  
C. P. Baveja ◽  
Gumma Vidyanidhi ◽  
Manisha Jain ◽  
Trishla Kumari ◽  
V. K. Sharma
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Extrapulmonary Tuberculosis ◽  
Multidrug Resistant ◽  
Multiple Drug ◽  
Drug Resistant ◽  
First Line ◽  
Antitubercular Drugs ◽  
Immunodeficiency Virus ◽  
Superficial Ulcer

The genitourinary tract is the most common site for extrapulmonary tuberculosis (TB). Penile TB is extremely rare comprising less than 1 % of all genital TB cases in males. It most commonly presents either as a superficial ulcer on the glans or around the corona. Diagnosis of penile TB is often difficult because it can mimic numerous other diseases. The association of TB with AIDS, and the increasing incidence of multiple drug resistance has further compounded the problem. The case described herein involves a patient with multidrug-resistant smear-positive penile TB that was undiagnosed initially due to the lack of clinical suspicion of TB, and once diagnosed failed to respond to first line antitubercular drugs because of multiple drug resistance.

scholarly journals Anti-Mycobacterial Drug Resistance in Japan: How to Approach This Problem?

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 19
Author(s):  
Keisuke Kamada ◽  
Satoshi Mitarai
Keyword(s):  
Drug Resistance ◽  
Time Course ◽  
Antimicrobial Agents ◽  
Treatment Success ◽  
Drug Susceptibility Testing ◽  
Health Concern ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Long Term Treatment

Mycobacteriosis is mainly caused by two groups of species: Mycobacterium tuberculosis and non-tuberculosis mycobacteria (NTM). The pathogens cause not only respiratory infections, but also general diseases. The common problem in these pathogens as of today is drug resistance. Tuberculosis (TB) is a major public health concern. A major challenge in the treatment of TB is anti-mycobacterial drug resistance (AMR), including multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Recently, the success rate of the treatment of drug-resistant tuberculosis (DR-TB) has improved significantly with the introduction of new and repurposed drugs, especially in industrialized countries such as Japan. However, long-term treatment and the adverse events associated with the treatment of DR-TB are still problematic. To solve these problems, optimal treatment regimens designed/tailor-made for each patient are necessary, regardless of the location in the world. In contrast to TB, NTM infections are environmentally oriented. Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus species (MABS) are the major causes of NTM infections in Japan. These bacteria are naturally resistant to a wide variation of antimicrobial agents. Macrolides, represented by clarithromycin (CLR) and amikacin (AMK), show relatively good correlation with treatment success. However, the efficacies of potential drugs for the treatment of macrolide-resistant MAC and MABS are currently under evaluation. Thus, it is particularly difficult to construct an effective treatment regimen for macrolide-resistant MAC and MABS. AMR in NTM infections are rather serious in Japan, even when compared with challenges associated with DR-TB. Given the AMR problems in TB and NTM, the appropriate use of drugs based on accurate drug susceptibility testing and the development of new compounds/regimens that are strongly bactericidal in a short-time course will be highly expected.

scholarly journals Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

2011 ◽  
Vol 55 (5) ◽  
pp. 2032-2041 ◽  
Author(s):  
Patricia J. Campbell ◽  
Glenn P. Morlock ◽  
R. David Sikes ◽  
Tracy L. Dalton ◽  
Beverly Metchock ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Dna Sequencing ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Second Line ◽  
First Line ◽  
Content Type ◽  
Line Drug

ABSTRACTThe emergence of multi- and extensively drug-resistant tuberculosis is a significant impediment to the control of this disease because treatment becomes more complex and costly. Reliable and timely drug susceptibility testing is critical to ensure that patients receive effective treatment and become noninfectious. Molecular methods can provide accurate and rapid drug susceptibility results. We used DNA sequencing to detect resistance to the first-line antituberculosis drugs isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) and the second-line drugs amikacin (AMK), capreomycin (CAP), kanamycin (KAN), ciprofloxacin (CIP), and ofloxacin (OFX). Nine loci were sequenced:rpoB(for resistance to RIF),katGandinhA(INH),pncA(PZA),embB(EMB),gyrA(CIP and OFX), andrrs,eis, andtlyA(KAN, AMK, and CAP). A total of 314 clinicalMycobacterium tuberculosiscomplex isolates representing a variety of antibiotic resistance patterns, genotypes, and geographical origins were analyzed. The molecular data were compared to the phenotypic data and the accuracy values were calculated. Sensitivity and specificity values for the first-line drug loci were 97.1% and 93.6% forrpoB, 85.4% and 100% forkatG, 16.5% and 100% forinhA, 90.6% and 100% forkatGandinhAtogether, 84.6% and 85.8% forpncA, and 78.6% and 93.1% forembB. The values for the second-line drugs were also calculated. The size and scope of this study, in numbers of loci and isolates examined, and the phenotypic diversity of those isolates support the use of DNA sequencing to detect drug resistance in theM. tuberculosiscomplex. Further, the results can be used to design diagnostic tests utilizing other mutation detection technologies.

scholarly journals A Systematic Follow-Up ofMycobacterium tuberculosisDrug-Resistance and Associated Genotypic Lineages in the French Departments of the Americas over a Seventeen-Year Period

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Julie Millet ◽  
Elisabeth Streit ◽  
Mylène Berchel ◽  
Anne-Gaël Bomer ◽  
Franziska Schuster ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Latin American ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Incidence Rates ◽  
Drug Resistant ◽  
East African ◽  
Mdr Tb

The population of the French Departments of the Americas (FDA) is highly influenced by the intense migratory flows with mainland France and surrounding countries of the Caribbean and Latin America, some of which have high incidence rates of tuberculosis (Haiti: 230/100,000; Guyana: 111/100,000; and Suriname: 145/100,000) and drug resistance. Since the development of drug resistance to conventional antituberculous drugs has a major impact on the treatment success of tuberculosis, we therefore decided to review carefullyMycobacterium tuberculosisdrug resistance and associated genotypic lineages in the FDA over a seventeen-year period (January 1995–December 2011). A total of 1239 cases were studied, including 153 drug-resistant and 26 multidrug-resistant- (MDR-) TB cases, representing 12.3% and 2.1% of the TB cases in our study setting. A significantly higher proportion ofM. tuberculosisisolates among relapse cases showed drug resistance to isoniazid (22.5%,P=0.002), rifampicin (20.0%,P<0.001), or both (MDR-TB, 17.5%;P<0.001). Determination of spoligotyping based phylogenetic clades showed that among the five major lineages observed—T family (30.1%); Latin-American and Mediterranean (LAM, 23.7%); Haarlem (H, 22.2%); East-African Indian (EAI, 7.2%); and X family (6.5%)—two lineages, X and LAM, were overrepresented in drug-resistant and MDR-TB cases, respectively. Finally, 19 predominant spoligotypes were identified for the 1239 isolates ofM. tuberculosisin our study among which 4 were significantly associated with drug resistance corresponding to SIT20/LAM1, SIT64/LAM6, SIT45/H1, and SIT46/undefined lineage.

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.

Sign in / Sign up

Export Citation Format

Share Document