XDR-TB Patients Research Articles

Toll-like receptor 2 (-196 to -174) del and TLR1 743 A > G gene polymorphism-a possible association with drug-resistant tuberculosis in the north Indian population.

The objective of this study is to analyze the association between TLR2 deletion (-196 to -174) and TLR1 743 A > G gene polymorphism with drug resistant tuberculosis (PTB, MDR-TB, and XDR-TB) in a population from Agra, Uttar Pradesh. The present case-control study included 101 pulmonary TB patients, 104 multidrug-resistant TB patients, 48 extremely drug-resistant TB patients, and 130 healthy and unrelated controls residing in the same locality. The genotyping method for TLR2 deletion (-196 to -174) was carried out by allele-specific polymerase chain reaction (PCR), and TLR1 743 A > G gene polymorphism was performed by hybridization probe chemistry in Roche Real-Time PCR. Genotype and allele frequencies were analyzed by the chi-square test. Cytokine levels were measured by ELISA and compared using Mann-Whitney and Kruskal-Wallis tests. The frequency of heterozygous (Ins/del) genotypes for TLR2 (-196 to -174) polymorphism was predominant in XDR-TB patients (0.57), whereas heterozygous A/G genotype for TLR1 743 A > G single nucleotide polymorphism (SNP) was predominant in healthy controls (0.57) for TLR1 743 A > G gene polymorphism. The heterozygous genotype of TLR2 deletion polymorphism was found to be significantly higher in XDR-TB (p = 0.0001). TLR1 743 A > G SNP, AG genotypes were found to be significantly associated with healthy controls than PTB (p = 0.047). The level of serum cytokines (IL-6, TNF-α, and IFN-γ) was also found to be significantly different among TB patients and healthy controls. The findings suggested that in the present population, the heterozygous (Ins/Del) genotype and deletion allele of TLR2 deletion (-196 to -174) polymorphism are associated with the risk for the development of drug-resistant TB. Furthermore, for TLR1 743 A > G gene polymorphism, A/G genotype, and G allele are found associated with healthy controls, suggesting the protective role against TB.

Profile and risk factors of pre-XDR-TB and XDR-TB patients in a national reference hospital for Sumatra region of Indonesia.

The low treatment rate, low treatment success rate and high mortality rate of patients with pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) need serious attention. The aim of this study was to describe the profiles of patients with pre-XDR-TB and XDR-TB cases and to determine associated risk factors of their incidence in Indonesia. A retrospective case-control study was conducted at H. Adam Malik General Hospital in Medan, North Sumatra of which all sensitive-drug TB (SD-TB), pre-XDR-TB, and XDR-TB patients aged 18 years or older treated between October 2019 to June 2022 were included. Chi-squared test or Kruskal Wallis test and multiple logistic regression were used to determine the risk factors associated with pre-XDR-TB and XDR-TB incidence. A total 16 patients of case group (15 pre-XDR-TB and one XDR-TB) and 116 SD-TB patients (control group) were included in the final analysis. Out of total patients within case group, 62.5% were male, 43.8% aged between 56-65 years, 62.5% graduated from high school or equivalent, and 25% were unemployed. The majority of patients had no comorbid (62.5%), had history of anti-TB treatment (93.8%), and had secondary resistance (93.8%). Multivariate analysis indicated that age (OR: 10.01; 95%CI: 1.49- 66.91, p=0.018) and previous history of anti-TB treatment (OR: 216.25; 95%CI: 18.62- 2511.60, p<0.001) were significantly associated with incidence of pre-XDR-TB and XDR-TB. This study highlights that having previous history of anti-TB treatment and older age are the predictors of the incidence of pre-XDR-TB and XDR-TB.

Bedaquiline, Delamanid, Linezolid, Clofazimine, and Capreomycin MIC Distributions for Drug Resistance Mycobacterium tuberculosis in Shanghai, China.

New antituberculosis drugs have recently been approved for the treatment of multidrug-resistant tuberculosis TB (MDR-TB). We aimed to describe the distributions of bedaquiline, delamanid, linezolid, clofazimine, and capreomycin MIC values for M. tuberculosis. M. tuberculosis clinical isolates were originally isolated from 2020 to 2021 from 1452 different pulmonary tuberculosis patients of the Shanghai Pulmonary Hospital in China. The drug susceptibility testing was performed using the Sensititre custom plates (SHTBMY) (TREK Diagnostic Systems, Thermo Fisher Scientific In., USA) consisting of a 96-well microtitre plate containing 4 (bedaquiline, delamanid, clofazimine, capreomycin) antimicrobial agents. MICs were determined for linezolid using a microdilution method. Based on the latest definitions, 156 (10.74%) were MDR-TB, 93 (6.40%) were pre-XDR-TB, and 27 (1.86%) were XDR-TB. The rate of BDQ resistance in cases of MDR-TB was 7.69%, while it was observed to be 10.75% in cases of pre-XDR-TB, and significantly higher at 37.04% in cases of XDR-TB. The lowest rate of drug resistance against M. tuberculosis was DLM (0.14%). For LZD, 11 (0.76%) clinical isolates were resistant, based on the CLSI breakpoint of 1μg/mL. The five strains with a MIC value of >32 for LZD resistance were XDR-TB isolates. Among all MDR, pre-XDR, and XDR isolates tested, LZD' MIC50 increased from 0.25 and 0.5 to 1μg/mL. The MIC90 value of LZD against XDR-TB isolates was 32μg/mL. For CFZ, six isolates with elevated MICs of ≥2μg/mL. CFZ's MIC50 and MIC90 values in all isolates were 0.12μg/mL and 0.25μg/mL, respectively. The study findings indicate that BDQ, DLM, CFZ, and LZD may exhibited excellent in vitro activity against MDR-TB isolates. Detection of resistance to BDQ and LZD was alarming for XDR-TB isolates. It is necessary to perform universal drug sensitivity testing for M. tuberculosis, especially MDR-TB and XDR-TB patients.

Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis.

A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment. Materials and Methods: A retrospective, prospective study was conducted where 307 patients with MDR-TB and XDR-TB pulmonary tuberculosis aged 18 to 75 years who received eTB treatment from 2016 to 2021 in St. Petersburg hospitals were analyzed. The analysis showed that the comorbidity level in MDR-TB and XDR-TB patients with TB treatment success and treatment failure was comparable with the use of the Charlson Comorbidity Index (CCI). The CCI demonstrated declining data in terms of TB treatment outcome period in both groups. A slight predominance of CCI score (3 to 4 points) in XDR-TB (22.7%) vs. MDR-TB (15.4%) patients was found. In the case of an TB treatment failure, the CCI level in MDR-TB vs. XDR-TB patients was characterized by a significantly higher rate of low magnitude (ranging from 1 to 2 points) in 21.1% vs. 4.5% (p < 0.05), which was higher in XDR-TB patients (ranging from 4 to 5 points, in 10.0% vs. 0, χ2 = 33.7 (p < 0.01)). Chronic viral hepatitis B and C infection, cardiovascular pathology, chronic obstructive pulmonary disease, and chronic alcoholism were found to be significant comorbidity factors that influenced the TB treatment success. Conclusions: It is evident that XDR-TB patients comprise a cohort with the most severe disease course due to comorbidities impacting TB treatment efficacy. The obtained data pointed to the need to determine comorbidity severity in patients with drug-resistant Mbt prior to administering TB treatment schemes.

Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

Antibiotic resistance acquisition versus primary transmission in the presentation of extensively drug-resistant tuberculosis.

Mycobacterium tuberculosis is the leading cause of mortality worldwide due to a single bacterial pathogen. Of concern is the negative impact that the COVID-19 pandemic has had on the control of tuberculosis (TB) including drug-resistant forms of the disease. Antimicrobial resistance increases the likelihood of worsened outcomes in TB patients including treatment failure and death. Multidrug-resistant (MDR) strains, resistant to first-line drugs isoniazid and rifampin, and extensively drug-resistant (XDR) strains with further resistance to second-line drugs (SLD), threaten control programs designed to lower TB incidence and end the disease as a public health challenge by 2030, in accordance with UN Sustainable Development Goals. Tackling TB requires an understanding of the pathways through which drug resistance emerges. Here, the roles of acquired resistance mutation, and primary transmission, are examined with regard to XDR-TB. It is apparent that XDR-TB can emerge from MDR-TB through a small number of additional resistance mutations that occur in patients undergoing drug treatment. Rapid detection of resistance, to first-line drugs and SLD, at the initiation of and during treatment, and prompt adjustment of regimens are required to ensure treatment success in these patients. Primary transmission is predicted to make an increasing contribution to the XDR-TB caseload in the future. Much work is required to improve the implementation of the World Health Organization-recommended infection control practices and block onward transmission of XDR-TB patients to contacts including health-care workers. Finally, limiting background resistance to fluoroquinolones in pre-XDR strains of M. tuberculosis will necessitate better antimicrobial stewardship in the broader use of this drug class.

Bedaquiline-based treatment for extensively drug-resistant tuberculosis in South Africa: A cost-effectiveness analysis.

BackgroundThe treatment success rate of conventional anti-tuberculosis (TB) regimens for extensively drug-resistant TB (XDR-TB) is low, resulting in high morbidity and healthcare cost especially in the high TB burden countries. Recent clinical findings reported improved treatment outcomes of XDR-TB with the bedaquiline (BDQ)-based regimens. We aimed to evaluate the cost-effectiveness of BDQ-based treatment for XDR-TB from the perspective of the South Africa national healthcare provider.MethodsA 2-year decision-analytic model was designed to evaluate the clinical and economic outcomes of a hypothetical cohort of adult XDR-TB patients with (1) BDQ-based regimen and (2) injectable-based conventional regimen. The model inputs were retrieved from literature and public data. Base-case analysis and sensitivity analysis were performed. The primary model outputs included TB-related direct medical cost and disability-adjusted life years (DALYs).ResultsIn the base-case analysis, the BDQ group reduced 4.4152 DALYs with an incremental cost of USD1,606 when compared to the conventional group. The incremental cost per DALY averted (ICER) by the BDQ group was 364 USD/DALY averted. No influential factor was identified in the sensitivity analysis. In probabilistic sensitivity analysis, the BDQ group was accepted as cost-effective in 97.82% of the 10,000 simulations at a willingness-to-pay threshold of 5,656 USD/DALY averted (1× gross domestic product per capita in South Africa).ConclusionThe BDQ-based therapy appeared to be cost-effective and showed a high probability to be accepted as the preferred cost-effective option for active XDR-TB treatment.

Efficacy of using bedaquiline in treatment of tuberculosis patients with multiple and extensive drug resistance

The objective: to compare treatment efficacy of pulmonary tuberculosis patients with multiple (MDR) and extensive drug resistance (XDR) using a standard chemotherapy regimen and the regimen containing bedaquiline.Subjects and Methods. A retrospective study was conducted to analyze treatment outcomes in 219 patients with pulmonary tuberculosis and MDR/XDR of Mycobacterium tuberculosis (MTB) aged 18-75 years old who were treated in in-patient and out-patient facilities of St. Petersburg from 2016 to 2019. Treatment outcomes were analyzed by subgroups formed taking into account resistance patterns and addition of bedaquiline to the treatment regimens: Ia – n = 94 (MDR TB; Bq-) and IIa ‒ n = 80 (XDR TB; Bq-); Ib ‒ n = 22 (MDR TB; Bq+) and IIb ‒ n = 23 (XDR TB; Bq+). Clinical and laboratory parameters of patients, the severity of comorbidity were assessed before the start of treatment, after 3, 6, 12-14 and 18-24 months of therapy, as well as after therapy completion and during the follow-up period. Statistical analysis was carried out using Statistica 10.0 and methods of parametric and nonparametric statistics and the SPSS 16.0 software, where p ≤ 0.05 was considered significant.Results. XDR TB patients in Subgroup IIb were significantly more likely to have a high level of comorbidity according to Charlson index (from 5 to 6 points) – in 34.7% of cases versus 5.0% in Subgroup IIa. At all stages of treatment in MDR TB patients with Bq+ (Ib), sputum conversion was recorded significantly more often versus patients of Subgroup Ia with Bq- when examined at all stages, with maximum effectiveness achieved by 18-24 months of treatment (90.9%). Treatment efficacy of XDR TB patients (IIb, Bq+) was also significantly higher versus treatment regimen containing no bedaquiline (60.8% (IIb, Bq+) versus 25.0% (IIa, Bq-), χ2 = 4.61, p &lt; 0.05).Conclusions. Achieved high efficacy of therapy in Subgroups Ib and IIb containing Bq provided a positive impact on treatment default rates, that were recorded in a low percentage of cases in those subgroups. An ineffective course of treatment in MDR TB patients treated with regimens containing no Bq was observed in 42.5% in Subgroup Ia, while this rate made only 0.09% in Subgroup Ib. Treatment effectiveness was the highest in XDR TB patients of Subgroup IIb when Bq was added to the treatment regimen.

Bedaquiline in the treatment of extensively drugresistant tuberculosis

Introduction. Extensive drug resistance (XDR) M. Tuberculosis (MBT) is considered the main factor that reduces the effectiveness of the treatment of TB patients around the world, including Russia. A significant role in improving the effectiveness of chemotherapy (CT) in people with resistant TB belongs to the introduction of new anti-TB drugs, the first of which was bedaquiline (LP-002281).Objective. To assess the profile of an XDR-TB patient receiving bedaquiline and the efficacy of chemotherapy regimens including bedaquiline in patients with XDR pulmonary tuberculosis.Materials and methods. The study is retrospective, non-comparative, descriptive. The data of 88 patients who received bedaquiline in the XDR-TB treatment regimen in anti-tuberculosis institutions of the Saratov region in 2017–2018.Results. Patients with chronic TB prevailed – 50/88 [56.8%, 95% CI 46.3–67.4], every fourth patient had a history of surgery. The cessation of bacterial excretion, confirmed by bacterioscopy, was achieved in 51/67 [76.1%, 95% CI 65.7–86.5] patients; by cultural method – in 47/67 [70,1%, 95% CI 59.0–81.3]. Negative sputum smear in a significant proportion of patients 43/51 [84.3%, 95% CI 52.4–75.9] was observed after 12 weeks of therapy, negative cultures in 36/47 [76.6%, 95% CI 41.6–65.9] – after 16 weeks.Discussion. Compared to individual patient analyzes – 43% success rate in the treatment of XDR-TB, in our cohort of XDR-TB patients treated with bedaquiline, the success rate was 53.4%, which is consistent with data from a large study describing the safety in 2017, tolerability and efficacy of bedaquiline and could be higher in the absence of “discontinuations from treatment”.Conclusion. The regimens of treatment of patients with XDR-tuberculosis with the inclusion of bedaquiline are effective in terms of the termination of bacterial excretion, confirmed by bacterioscopy and culture in patients with a complex course of a specific process with previous ineffective therapy.

Estimation of Success Rate of Treatment of XDR-TB admitted in a Nodal DRTB Centre

Background: Extensively drug-resistant TB is still a serious challenge in India, and before the introduction of new anti-tuberculosis drugs these patients were treated with a conventional regimen for XDR-TB according to the guidelines of RNTCP at that time for almost 24 to 36 months. Objective: To estimate the outcome of treatment of XDR-TB patients attended at our DRTB site and put under the conventional regimen during the period 2014-2017 according to protocol laid down by PMDT at that time i.e. 2014 to 2017.Methods: In this retrospective study, we selected 41 patients admitted with XDR-TB, in our DRTB site from April 2014 to March 2017. We studied their treatment outcomes (cured, treatment completed, treatment failure, death, and treatment after default) 30 to 36 months after treatment initiation according to PMDT (2014 -2017). Results: Among the 41 cases of XDR-TB that were included in the study 28 were male, 30 resided in rural areas and 28 had a BMI &lt; 18.5 kg/m2. 13 (32%) patients were successfully treated but 21 (50%) patients died during the treatment and treatment failure happened in 6 (15%) patients. Patients with low BMI (&lt; 18.5 kg/m2) had poor success rate (7%) and all the 21 patients who died during treatment, had low BMI. Conclusion: The present study finds that only one in every three XDR-TB cases are successfully treated with conventional second-line antitubercular drugs and this finding is the same as found in the NTEP report. Nearly half of the patients die. The patients with low BMI respond worst.

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study

BackgroundThere was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients.MethodsThis retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan–Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant.ResultsA total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47–3.53), than those who did not (median: 10 months, 95% CI: 5.24–14.76) (p-value < 0.001, Log-rank test). Patient’s age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7–50.2), 69.9% (95%CI: 61.7–77.2) and 84.9% (95%CI: 78.1–90.3), specificities were respectively, 82.8% (95%CI: 76.9–87.6), 74.6% (95%CI: 68.2–80.4) and 69.4% (95%CI: 62.6–75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7–70.8), 72.7% (95%CI: 67.7–77.2) and 75.8% (95%CI: 71.0–80.1).ConclusionIn forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review

BackgroundExtensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. MethodsWe conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. ResultsOut of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). ConclusionTreatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

Risk Factors of Prolonged QTc Interval in Patients with Drugs-Resistant Tuberculosis

Background: Drug-Resistant Tuberculosis (DRTB) is still one of the biggest health problems worldwide. In 2016, WHO published new guidelines for DRTB management using 7 second-line drugs that only required 9-11 months of treatment with a higher success rate. Unfortunately, one of the side effects was the possibility of a prolonged QT-c interval on electrocardiography. However, to date there have been no known factors which increased the risk of QTc prolongation in DRTB patients.Methods: This was a retrospective cohort study that analyzed the medical records of 50 DRTB patients who underwent treatment from August 2017 to August 2020 at the DRTB Clinic of Adam Malik Hospital Medan. Statistical analysis was performed using logistic regression to determine the factors which increased the risk of QTc prolongation in DRTB patients.Results: Of the 50 study samples consisting of 40 MDR TB patients, 9 pre-XDR TB patients and 1 XDR TB patient, 14 (28%) subjects were found to have QTc prolongation. There were no correlation between the regimen type (P = 0.51), age (P = 0.40), sex (P = 0.74), nutritional status (P = 0.35) and comorbid diseases (P = 0.31) on the prolongation of QTc interval. Patients receiving clofazimine had a greater percentage (78.6% vs 21.4%) to experience prolonged QTc interval, although not statistically significant (P = 0.41). Conclusion: Treatment regimen, age, sex, nutritional status and comorbid disease were not associated with prolonged QTc interval in DRTB.

Treatment outcomes among childhood extensively drug-resistant tuberculosis patients in Pakistan.

Treatment outcomes of childhood XDR-TB patients in Pakistan are better than in adult patients but still disappointing https://bit.ly/3rkQ9sw

Evaluation of screening strategies of multidrug-resistant tuberculosis among pulmonary tuberculosis patients of the different risk levels

Objective: To evaluate the detection of MDR-TB and XDR-TB patients and to provide evidence for further improvement of MDR-TB and XDR-TB screening strategy. Methods: Patients who were under drug resistance surveillance, registered and reported by the TB Management Information System of the Chinese Disease Prevention and Control Information System from 2012 to 2019 and resided in Guizhou province were retrospectively analyzed. The contribution of five high-risk subgroups to detection of MDR/XDR-TB were evaluated using population attributable risk proportion (PARP). Results: Of the 18 506 cases under drug resistance surveillance, patients who were male, aged between 25 and 54 years, with drug-resistant TB or with MDR/XDR-TB accounted for 68.65% (12 705/18 506), 47.69% (8 826/18 506), 15.90% (2 943/18 506) or 5.42% (1 003/18 506), respectively. Five high-risk subgroups made significant contributions to the detection of MDR/XDR-TB with a PARP of 57.00%. Specifically, the PARP were 21.70%, 19.49%, 11.90% and 2.30% for patients that were relapse and return, failed initial treatment, chronic/retreatment failure and smear-positive at the end of the second or third month, respectively. The detection rate of MDR/XDR-TB in high-risk groups was 15.89% (578/3 637) while in low-risk groups was 2.86% (425/14 869). Conclusions: Number of patients under drug resistance surveillance and the detection of MDR/XDR-TB trended to increase in Guizhou province from 2012 to 2019. The detection rate of MDR/XDR-TB in high-risk groups was higher than low-risk groups.

Risk Factors for Poor Outcomes Among Patients with Extensively Drug-Resistant Tuberculosis (XDR-TB): A Scoping Review.

In recent years, there has been an upsurge in cases of drug-resistant TB, and strains of TB resistant to all forms of treatment have begun to emerge; the highest level of resistance is classified as extensively drug-resistant tuberculosis (XDR-TB). There is an urgent need to prevent poor outcomes (death/default/failed treatment) of XDR-TB, and knowing the risk factors can inform such efforts. The objective of this scoping review was to therefore identify risk factors for poor outcomes among XDR-TB patients. We searched three scientific databases, PubMed, Scopus, and ProQuest, and identified 25 articles that examined relevant risk factors. Across the included studies, the proportion of patients with poor outcomes ranged from 8.6 to 88.7%. We found that the most commonly reported risk factor for patients with XDR-TB developing poor outcomes was having a history of TB. Other risk factors were human immunodeficiency virus (HIV), a history of incarceration, low body mass, being a smoker, alcohol use, unemployment, being male, and being middle-aged. Knowledge and understanding of the risk factors associated with poor outcomes of XDR-TB can help policy makers and organizations in the process of designing and implementing effective programs.

Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019.

Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3-4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

THE INVOLUNTARY DETENTION AND ISOLATION OF PATIENTS INFECTED WITH EXTREME RESISTANT TUBERCULOSIS (XDR-TB): IMPLICATIONS FOR PUBLIC HEALTH, HUMAN RIGHTS AND INFORMED CONSENT Minister of Health, Western Cape v Goliath 2009 2 SA 248 (C)

Public health-care providers (public hospitals) and related health-care services in South Africa have in recent times been under severe strain due to the seemingly uncontrollable increase in dangerous infectious airborne diseases like Extreme Resistant Tuberculosis (hereinafter “XDR-TB”). Ultimately these health-care providers/services have been challenged, not only in the diagnosis and treatment of XDR-TB patients, but specifically to control and curtail the spread thereof by effectively managing sufferers by way of forced isolation and monitoring to ensure that they abide by the rules and strict treatment regime related to XDR-TB. The said challenge hasbecome exacerbated specifically in public health-care facilities where patients suffering from XDR-TB fail to abide by the treatment regime and regularly abscond from follow-up appointments, posing a real threat of infection to the community at large. Consequently public health-care providers and communities have increasingly questioned whether it is possible to invoke some mechanism legally whereby the involuntary isolation of patients with XDR-TB in State-funded health-care facilities could be effected. It goes without saying that such a mechanism (by way of a court order/court authorisation) would have a definite and marked influence on a patient’s right to bodily integrity and freedom (as contemplated in s 12 of the Constitution of the Republic of South Africa, 1996) and will pose significant challenges to any constitutional limitation (as contemplated in s 36) and related legislation (such as the National Health Act 61 of 2003). Ultimately the question under consideration is whether the public’s right to be protected from potentially dangerous infectious diseases constitutionally trumps the right of an individual sufferer to bodily integrity. It is in this regard that the present case under discussion offers far-reaching perspectives.

Evaluating the Frequency of Resistance to Pyrazinamide Among Drug-resistant Strains of Mycobacterium tuberculosis in Isfahan, Iran

Background: Pyrazinamide is one of the most important first-line medications for the treatment of tuberculosis and an alternative intake for MDR-TB and XDR-TB patients. Objectives: The purpose of this study was to evaluate resistance to pyrazinamide in the isolates resistant to the Mycobacterium tuberculosis drug in patients in the city of Isfahan. Methods: In this study, the drug susceptibility test was performed with pyrazinamide using the proportion method and PZA assay on 47 isolates resistant to Mycobacterium tuberculosis. Then, the mutations of the pncA and rpsA genes of the isolates resistant to pyrazinamide were evaluated by the sequencing method. Results: According to the proportion method, 19 cases were resistant to pyrazinamide, 16 of which had mutations in their pncA and rpsA genes. Besides, five new mutations were recorded, and three isolates lacked mutations in the mentioned genes. Conclusions: Pyrazinamide resistance is high in MDR-TB and INH mono-resistant isolates. Therefore, evaluating the susceptibility to pyrazinamide in patients with MDR-TB before the initiation of treatment with pyrazinamide is considered essential.

Clinical implications of high-risk mutations in drug resistant tuberculosis (DR-TB): An observational cohort study

Genotype MTBDRsl [SL-LPA] was endorsed as a tool for early diagnosis of fluoroquinolones (FQ) and injectable second-line TB drugs (SLID) resistance in DR-TB. Correlation between specific genetic mutations using this tool and clinical outcome has not hitherto been studied in India. We conducted a observational cohort study to evaluate the predictive value of specific mutations for bad outcome. Our study identified 15 different types of gyrA mutations, commonest being A90V and D94G. Poor outcome was associated with mutations D94G and D94N/D94Y.Most XDR-TB patients harbored the high risk mutation of A1401G. Hence information of specific mutations using SL-LPA can help prognosticate and design appropriate treatment regimens.