Acquired and Transmitted Multidrug Resistant Tuberculosis: The Role of Social Determinants.
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ABSTRACT:
SUBMITTER: Odone A
PROVIDER: S-EPMC4713093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIncreasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.MethodsTo assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC.ResultsIn total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance.ConclusionsTreatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.
| S-EPMC4184341 | biostudies-literature
Project description:Multi-drug resistance (MDR) has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. This study described the characteristics and risk factors associated with MDR-TB among 287 cases and 291 controls in Henan province, China.A hospital-based case-control study was conducted between June 2012 and December 2013. The study subjects were selected using multistage probability sampling. Multivariate conditional logistic regression models were used to determine the risk factors associated with MDR-TB.The following risk factors for MDR-TB were identified: previous TB treatment (AOR = 4.51, 95% CI: 3.55-5.56), male sex (AOR = 1.09, 95% CI: 0.24-1.88), high school or lower education degree (AOR = 1.87, 95% CI: 1.27-2.69), unemployment (AOR = 1.30, 95% CI: 0.78-2.52), long distance of residence from the health facility (AOR = 6.66,95% CI: 5.92-7.72), smoking (AOR = 2.07, 95% CI: 1.66-3.19), poor knowledge regarding MDR-TB (AOR = 2.06, 95% CI: 1.66-2.92), traveling by foot to reach the health facility (AOR = 1.85, 95% CI: 1.12-3.09), estimated amount of time to reach the health facility was greater than 3 h (AOR = 1.42, 95% CI: 0.51-2.35), social stigma (AOR = 1.17, 95% CI: 0.27-2.03), having an opportunistic infection (AOR = 1.45, 95% CI: 0.58-2.4), more than 3 TB foci in the lungs (AOR = 1.98, 95% CI: 1.49-3.25), total time of first treatment was more than 8 months (AOR = 1.39, 95% CI: 0.65-2.54), adverse effects of anti-TB medication (AOR = 2.39, 95% CI: 1.40-3.26), and more than 3 prior episodes of anti-TB treatment (AOR = 1.83, 95% CI: 1.26-2.80).The identified risk factors should be given priority in TB control programs. Additionally, there is a compelling need for better management and control of MDR-TB, particularly through increasing laboratory capacity, regular screening, enhancing drug sensitivity testing, novel MDR-TB drug regimens, and adherence to medication.
| S-EPMC4715352 | biostudies-other
Project description:In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed using Sanger sequencing to detect mutations conferring LZD resistance. Of 277 patients in our cohort, 115 (115/277, 41.5%) with prior LZD exposure yielded 19 (19/277, 6.9%) isolates exhibiting LZD resistance. The LZD resistance rate of LZD-exposed group isolates significantly exceeded the corresponding rate for non-exposed group isolates (P = 0.047). Genetic mutations were observed in 10 (52.6%, 10/19) LZD-resistant isolates, of which a Cys154Arg (36.8%, 7/19) substitution within ribosomal protein L3 was most prevalent. Analysis of sequential positive cultures obtained from 81 LZD-treated patients indicated that cultured organisms obtained from most patients (85.2%, 69/81) retained original LZD MIC values; however, organisms cultured later from two patients exhibited significantly increased MIC values that were attributed to the rplC substitution T460C. Overall, LZD resistance was detected in 6.9% of patients of an MDR-TB cohort in China. Low rate of acquired LZD resistance was noted in MDR-TB treated with BDQ-LZD combination.
| S-EPMC8126624 | biostudies-literature
Project description:We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.
| S-EPMC7543851 | biostudies-literature
Project description:Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ?1 to ?5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.
| S-EPMC4725381 | biostudies-literature
Project description:BACKGROUND:Multidrug-resistant tuberculosis (MDR-TB) is burgeoning globally, and has been a serious challenge in TB management. Clinically, the ability to identify MDR-TB is still limited, especially in smear-negative TB. The aim of this study was to develop a nomogram for predicting MDR-TB. METHODS:Demographics and clinical characteristics of both MDR-TB and drug-susceptible TB patients were utilized to develop a nomogram for predicting MDR-TB. The LASSO regression method was applied to filter variables and select predictors, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Moreover, calibration analysis and decision curve analysis (DCA) of the model were performed. This study involved a second analysis of a completed prospective cohort study conducted in a country with a high TB burden. RESULTS:Five variables of TB patients were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.759 (95% CI, 0.719-0.799), and in the internal validation, the AUC was 0.757 (95% CI, 0.715-0.793). The predictive model was well-calibrated, and DCA showed that if the threshold probability of MDR-TB was between 70 and 90%, using the proposed nomogram to predict MDR-TB would obtain a net benefit. CONCLUSIONS:In this study, a nomogram was constructed that incorporated five demographic and clinical characteristics of TB patients. The nomogram may be of great value for the prediction of MDR-TB in patients with sputum-free or smear-negative TB.
| S-EPMC7276074 | biostudies-literature
Project description:In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia.
| S-EPMC3647667 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-09-25 | GSE269919 | GEO
Project description:Multidrug-resistant (MDR) tuberculosis (TB) has been emerging at an alarming rate over the last few years. It has been estimated that about 3% of all pediatric TB is MDR, meaning about 30,000 cases each year. Although most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with extensively drug-resistant (XDR) TB had limited treatment options and no standard regimen. The main objective of this manuscript is to discuss our present knowledge of the management of MDR- and XDR-TB in children, focusing on the characteristics and available evidence on the use of two promising new drugs: bedaquiline and delamanid. PubMed was used to search for all of the studies published up to November 2020 using key words such as "bedaquiline" and "delamanid" and "children" and "multidrug-resistant tuberculosis" and "extensively drug-resistant tuberculosis". The search was limited to articles published in English and providing evidence-based data. Although data on pediatric population are limited and more studies are needed to confirm the efficacy and safety of bedaquiline and delamanid, their use in children with MDR-TB/XDR-TB appears to have good tolerability and efficacy. However, more evidence on these new anti-TB drugs is needed to better guide their use in children in order to design effective shorter regimens and reduce adverse effects, drug interactions, and therapeutic failure.
| S-EPMC8156326 | biostudies-literature
Project description:BackgroundDespite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.Methods and findingsWe developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.ConclusionsTreatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
| S-EPMC1483913 | biostudies-literature