Drug-resistant Tuberculosis Patients Research Articles

Pyrazinamide resistance due to pncA gene mutation and its association with treatment outcome among tuberculosis patients of South India- A longitudinal observational study

IntroductionMycobacterium tuberculosis has been extensively studied for mutations leading to drug resistance. Pyrazinamide is a drug acting on the semi-dormant bacteria that is responsible for relapse of tuberculosis. This drug helped reduce the treatment duration of tuberculosis from nine to six months. However, this drug is not being screened for resistance along with Rifampicin and Isoniazid. Aims and objectivesThis study aimed to estimate the proportion of pncA gene mutation among tuberculosis patients and its association between treatment outcomes, clinical characteristics, and phenotypic drug resistance. Methodology: A total of 154 samples included 73 drug-resistant and 81 drug-susceptible isolates. The isolates were subjected to DNA extraction and amplification using conventional PCR. The PCR product was sequenced by the Sanger sequencing method, and phenotypic drug susceptibility testing was done using the broth dilution method. The association of this gene with the treatment outcome was done by following up with the patients till the end of the regimen. ResultsNone of the drug susceptible tuberculosis patients showed significant non-synonymous mutations. Among the drug-resistant TB patients, seven unique significant mutations out of 73 isolates (9.6%) were distributed among Isoniazid-resistant tuberculosis and Multi-Drug Resistant Tuberculosis isolates. No association was found between the mutations and the clinical characteristics of the subjects harboring these isolates. ConclusionThis study estimated seven unique mutations in drug-resistant tuberculosis and none in drug-sensitive tuberculosis. Isolates harboring was not significantly associated with the participant's treatment outcome and other clinical characteristics. The pyrazinamide resistance testing by the phenotypic and genotypic methods was found to be in concordance.

Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment

Drug resistance to tuberculosis (TB) has become an obstacle in eliminating tuberculosis. The transmission of drug-resistant TB from patients increases the incidence of primary drug-resistant (DR) TB in individuals who are in close contact. Therefore, it is necessary to incorporate an immunological approach into preventive therapy. This study focuses on the activity of lysosomal enzymes, oxygen bursts, and the attachment ability of macrophages among individuals diagnosed with active drug-resistant TB compared with close contacts with latent TB or healthy cases. We measured macrophage oxygen burst ability (Water-soluble tetrazolium salt (WST) test, Nitric Oxide production, and myeloperoxidase activity) and the degradative ability of lysosomes (activity of the β-glucuronidase and acid phosphatase enzymes). Six active DR-TB patients and 18 close-contact cases (8 Latent Tuberculosis Infection (LTBI); 10 healthy) were recruited at Universitas Indonesia Hospital. The macrophage attachment of the LTBI group was higher than in the other groups. NO production, myeloperoxidase activity, β-glucuronidase, and acid phosphatase were higher in the active DR-TB group. A negative correlation was uncovered between phagocytosis and NO production, myeloperoxidase activity, and lysosomal enzymes. The difference in macrophage function is expected to be a further reference in active DR-TB treatment or preventive therapy.

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis

ObjectiveWe aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors.MethodsPubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software.ResultsA total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB.ConclusionPatients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time.This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Vitamin D, Body Mass Index, and Total Lymphocyte Count in Drug-Sensitive and Drug-Resistant Tuberculosis Patients in Banjarmasin

Introduction: Tuberculosis (TB) remains a global health problem that causes high morbidity and mortality. Based on its classification, TB is divided into drug-sensitive (DS) and drug-resistant (DR). Several risk factors susceptible to TB are malnutrition with low body mass index (BMI), vitamin D deficiency (VDD), and low total lymphocyte count (TLC) related to low immune status. This study aimed to examine the relationship between vitamin D (VD), BMI, and TLC in the TB population in Banjarmasin. Methods: This was an analytic observational study with a cross-sectional design. The total study sample was 42 patients, confirmed by rapid molecular testing, who had not been treated for TB in Banjarmasin from January to May 2023 and met the inclusion and exclusion criteria. Chi-Square and Fisher's exact statistical tests were used to see the relationship between VD, BMI, and TLC in DS TB and DR TB. Results: The median age of DS TB was 38 (24-52) years old, and DR TB was 51 (37-58) years old. Most of the gender was male (24 patients/57.1%). There was a statistically significant difference between VD and BMI in DS TB and DR TB (p = 0.048; p = 0.019). There was a significant relationship between VD and TLC in DS TB and DR TB (p = 0.048). Conclusion: VD and BMI significantly differed in DS TB and DR TB. There was a significant correlation between VD and TLC in TB patients.

Healthcare seeking behavior and delays in case of Drug-Resistant Tuberculosis patients in Bangladesh: Findings from a cross-sectional survey.

The emergence of Drug-Resistant Tuberculosis (DR-TB) has become a major threat globally and Bangladesh is no exception. Delays in healthcare seeking, proper diagnosis and initiation of treatment cause continuous transmission of the resistant tubercule bacilli through the communities. This study aimed to assess the different health care-seeking behaviors and delays among DR-TB patients in Bangladesh. A prospective cross-sectional study was conducted from November to December 2018, among 92 culture positive and registered DR-TB patients in four selected hospitals in Bangladesh. Data were collected through face-to-face interviews with survey questionnaire as well as record reviews. Among the 92 study participants, the median patient delay was 7 (IQR 3, 15) days, the median diagnostic delay was 88 (IQR 36.5, 210), the median treatment delay was 7 (IQR 4,12) days, and the median total delay among DR-TB patients was 108.5 (IQR 57.5, 238) days. 81.32% sought initial care from informal healthcare providers. The majority (68.48%) of the informal healthcare providers were drug sellers while 60.87% of patients sought care from more than four healthcare points before being diagnosed with DR-TB. The initial care seeking from multiple providers was associated with diagnostic and total delays. In Bangladesh, DR-TB cases usually seek care from multiple providers, particularly from informal providers, and among them, alarmingly higher healthcare-seeking related delays were noted. Immediate measures should be taken both at the health system levels and, in the community, to curb transmission and reduce the burden of the disease.

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.

Associations between air pollutants and acute exacerbation of drug-resistant tuberculosis: evidence from a prospective cohort study

BackgroundShort-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines.ObjectiveTo investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM10, PM2.5, SO2, NO2, CO and O3) based on a large prospective cohort in Anhui Province, China.MethodPatients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution.ResultsShort-term NO2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment.ConclusionsNO2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China.

Global adoption of 6-month drug-resistant TB regimens: Projected uptake by 2026.

The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3-4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time. Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs. Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients. The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation.

Comparison of Nucleotide MALDI-TOF MS with Xpert MTB/RIF for Rifampicin Susceptibility Identification and Associated Risk Factors of Rifampicin Resistance Among Drug Resistant Mycobacterium tuberculosis.

Nucleotide-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS) is an emerging molecular technology used for the diagnosis of tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB)and its drug resistance. This study aimed to compare the ability of nucleotide MALDI-TOF MS to detect rifampicin (RIF) resistance in drug-resistant TB (DR-TB) patients with Xpert MTB/RIF and to analyze the disparate results individually. Additionally, potential factors associated with rifampicin resistance among DR-TB patients in Qingdao were investigated. A retrospective study was conducted at Qingdao Chest Hospital, and patients with DR-TB were enrolled. Corresponding frozen isolates were recovered and subjected to nucleotide MALDI-TOF MS, Xpert MTB/RIF, and phenotypic drug susceptibility testing (pDST). Sanger sequencing was performed for the discordant results of nucleotide MALDI-TOF MS and Xpert MTB/RIF. Univariate and multivariate logistic regression analyses were used to identify potential factors associated with rifampicin resistance among patients with DR-TB. A total of 125 patients with DR-TB (18.8%, 125/668) were enrolled in this study from May 1 to July 31, 2023. Rifampicin-resistant (DR-TB/RR, 29) and rifampicin-sensitive (DR-TB/RS, 96) groups were divided according to the pDST results. Nucleotide MALDI-TOF MS performed better than Xpert MTB/RIF in terms of sensitivity, specificity, accuracy, and agreement with pDST. Only six cases had inconsistent results, and the sequencing results of five cases were identical to nucleotide MALDI-TOF MS. Furthermore, chest pain (aOR=12.84, 95% CI, 2.29-91.97, p=0.005), isoniazid sensitivity (aOR=0.14, 0.02-0.59, p=0.013), and ethambutol sensitivity (aOR=0.02, 0.00-0.10, p=0.000) were potential factors associated with rifampicin resistance among DR-TB patients in Qingdao. The overall concordance between nucleotide MALDI-TOF MS and Xpert MTB/RIF was 95.2%, with the former performing better in determining rifampicin susceptibility among DR-TB cases in Qingdao. Chest pain, isoniazid, and ethambutol resistance might be factors associated with RIF resistance among patients with DR-TB in Qingdao.

Burden of drug-resistant tuberculosis among contacts of index cases: a protocol for a systematic review

IntroductionPeople having close contact with drug-resistant tuberculosis (DR-TB) patients are at increased risk of contracting and developing the disease. However, no comprehensive review has been undertaken to estimate the burden...

Therapeutic Drug Monitoring of Linezolid in Drug-Resistant Tuberculosis Patients: Clinical Factors and Hematological Toxicities.

Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity. This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728. Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

Risk factors of treatment interruptions among drug-sensitive and drug-resistant pulmonary tuberculosis patients - A study from South Delhi, New Delhi, India

BackgroundA variety of factors influence adherence to the lengthy duration of anti-tuberculosis treatment, making it a complicated and dynamic problem. The objective of this study was to investigate the treatment interruption patterns using pre-defined criteria among a cohort of pulmonary tuberculosis patients and to elicit the associated factors. MethodsThis prospective, observational study was conducted between October 2016 to May 2018. All smear and culture positive pulmonary tuberculosis patients (age ≥ 14 years) enrolled between October 1, 2016 to March 31, 2017 across 3 Designated Microscopy Centers (DMCs) were included and followed up till end of treatment for outcome in drug-sensitive, and till interim outcome at 6 months for drug-resistant TB patients. Patterns and reasons for interruptions were recorded as per the study protocol. Results171 patients were enrolled in this study, of which 135 (78.94 %) were on Category-I and Category-II treatment (drug-sensitive tuberculosis), 23 (13 %) were multidrug-resistant (MDR) and 13 (8 %) were extensively drug resistant (XDR) tuberculosis patients. Among the drug-sensitive group, 65 (48 %) patients completed their treatment without any interruption while 70 (52 %) patients interrupted with at least one missed dose. Among the 36 MDR/XDR patients, 19 (53 %) patients did not interrupt treatment, but 17 (47 %) patients interrupted with at least one missing dose. The 87 patients in both sub-groups interrupted for 232 times/episodes of which 140 were short and 84 were long interruptions. The main reasons for interruption were found to be busy schedule in 63 (29 %) patients, adverse drug reactions in 40 (18.4 %) and comorbidities in 43 (19.8 %) patients. Feeling of early improvement/no improvement in 23 (10.5 %) patients, addictions in 27 (12.4 %) patients, lack of family support in 14 (6.4 %), unawareness of dosage and duration of treatment in 7 (3.20 %) patients were other common reasons. ConclusionThe plurality of patients studied were found to be in the younger age group i.e., 14–25 years (n = 75), constituting nearly 44 % of all the patients included and male treatment interrupters (62 %) outnumbered the females (38 %), possibly owing to work schedule or addictions. The majority of interruptions were related to patient related factors (93.5 %), followed by DOTS provided factors (6.40 %) and system related factors (3.01 %). Further studies should be conducted to classify the factors of treatment interruptions in detail and also to study the impact of these interruptions’ patterns on final outcomes.

Factors associated with mortality among laboratory-diagnosed drug-resistant tuberculosis patients on treatment, KwaZulu-Natal Province, 2017-2019.

tuberculosis (TB) remains a leading cause of death in South Africa. KwaZulu-Natal (KZN) is one of the provinces with a high burden of TB/drug-resistant TB cases and deaths. We determined predictors for mortality among drug-resistant TB patients on treatment in KZN province. we conducted a retrospective cohort study using secondary data from the Electronic Drug-Resistant Tuberculosis Register. We used a modified Poisson regression model with robust standard errors to determine predictors for drug-resistant TB mortality. of the 7,692 eligible patients, 1,234 (16.0%) died. Males predominated (707, 57.3%) and the median age was 36 years (Interquartlile Range: 29-45 years). The majority (978, 79.2%) were HIV-TB co-infected with 911 (93%) on antiretroviral treatment (ART). The predictors included HIV-TB co-infection without ART (aIRR 3.4; 95% CI: 2.3-5.1), unknown ART status (aIRR: 1.8; 95% CI: 1.4-2.3), aged ≥60 years (aIRR: 2.1; 95% CI: 1.6-2.7), previous drug-resistant TB (aIRR: 1.5; 95% CI: 1.2-1.8) and exposure to second-line drugs (aIRR: 1.7; 95% CI: 1.4-2.0). Other predictors were hospitalization during treatment initiation (aIRR 2.5; 95% CI 2.0-3.1), initiation in other treatment facilities (aIRR: 2.2; 95% CI: 1.6-2.9) and rifampicin-resistant (aIRR: 1.2; 95% CI: 1.1-1.4). Bedaquiline fumarate was a significant protective factor against death (aIRR: 0.5; 95% CI: 0.4-0.5). older age, HIV co-infection without ART, hospitalization for treatment initiation, exposure to second-line drugs and a previous episode of drug-resistant TB were predictors for DR-TB mortality. Early treatment initiation and provision of antiretroviral treatment for all co-infected patients may reduce DR-TB mortality in the Province.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

Pyrazinamide Resistance among Multi Drug Resistant Tuberculosis Patients in Karnataka: Cross Sectional Study from a Referral Centre

This study aimed to investigate the rate of occurrence of pyrazinamide (PZA) resistance among patients with MDR-TB from the clinical specimens submitted to a referral centre in Bengaluru, Karnataka. PZA has been used for almost 50 years as first line drug for short course chemotherapy against MTB and its inclusion has significantly shortened the treatment duration to 6 months. However, resistance to PZA is associated with poor treatment outcomes and its drug susceptibility testing (DST) is not routinely performed in public health laboratories in India due to technical difficulties. This study followed a structured approach to investigate PZA resistance among MDRTB patients in Karnataka. Relevant demographic and clinical information was collected from Laboratory registers. The specimens yielding the growth of Mycobacterium tuberculosis were subjected to DST for PZA using validated techniques and the rate of PZA resistance was determined. Our results showed 4% of PZA resistance among MDRTB specimens. These results can contribute to the understanding of local epidemiology of drug resistant TB and update public health strategies for TB control in a particular geographical region. The findings may highlight the need for routine DST for PZA in public health laboratories in India and further research to better understand the associated factors with PZA resistance. This study also emphasizes the importance of continued surveillance of drug resistance patterns to guide evidence-based interventions for TB control and management.

Treatment Duration and Drug Regimen Correlation with Side Effects Incidence in Drug-Resistant Tuberculosis (DR-TB) Patients at Pulmonary Hospital

The bacteria Mycobacterium tuberculosis causes Drug-Resistant Tuberculosis (DR-TB). Excessive use of drugs can result in drug resistance with various side effects. This study aimed to analyze the correlation between the treatment duration and drug regimen with the side effects incidence in DR-TB Patients at Pulmonary Hospital Dr. M. Goenawan Partoidigdo (RSPG) Bogor. This is an observational study with a cross-sectional design. Subjects were selected with purposive sampling methods based on inclusion and exclusion criteria. The research showed that DR-TB patients were mostly male (50.2%) with productive age (46.1%). The most common DR-TB treatment experienced by patients in the advanced phase, generally for 9-24 months (75.3%), and the type of drug side effect most experienced was gastrointestinal disorders, that is nausea (55.1%). The use of standard conventional drug regimens mostly in Z, E, Eto, Km, Lfx, Cs (Pyrazinamide, Ethambutol, Ethionamide, Kanamycin, Levofloxacin, Cycloserine) of 51.4%. The chi-square analysis showed no significant correlation between the treatment duration and the incidence of side effects. At the same time, there was a meaningful correlation between the drug regimen (short-term, long-term, and conventional standard regimen) and the side effects incidence. The suspected drugs causing gastrointestinal side effects were pyrazinamide, ethambutol, ethionamide, and levofloxacin. The side effects of arthritic arthralgia were suspected to be caused by pyrazinamide, ethionamide, and levofloxacin.

Efficacy of pretomanid-containing regiments for drug-resistant tuberculosis: A systematic review and meta-analysis of clinical trials.

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multidrug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76-185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86-196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Peran Bedaquiline dan Penggunaannya pada Tuberkulosis Resisten Obat : Sebuah Kajian Naratif

Tuberculosis, caused by infection with Mycobacterium tuberculosis, is still a global concern. The existence of resistance to the first line of anti-TB, namely isoniazid and rifampicin, is an urgent need for the development of new drugs that are effective and safe against tuberculosis. Bedaquiline has received approval from the FDA as a new anti-TB drug discovered to treat drug-resistant tuberculosis. This article aims to review the role of bedaquiline in the treatment of drug-resistant tuberculosis mechanisms, evidence, effectiveness, and adverse events. This narrative review uses a literature study approach by identifying various literature and research articles through databases as relevant references. Bedaquililine belongs to the diarylquinoline class inhibits ATP-synthase activity and suppresses the growth of active and dormant mycobacteria. Various clinical trials conducted previously have evaluated the use of bedaquiline-based regimens for the treatment of adults with drug-resistant tuberculosis. Bedaquiline-based regimens showed efficacy and were generally well tolerated in numerous studies. Currently, further evaluation is needed regarding its efficacy, safety, and tolerability in drug-resistant tuberculosis patients in Indonesia.

Assess the Diagnostic Accuracy of GeneXpert to Detect Mycobacterium tuberculosis and Rifampicin-Resistant Tuberculosis among Presumptive Tuberculosis and Presumptive Drug Resistant Tuberculosis Patients

GeneXpert MTB/RIF is a rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to assess the diagnostic precision of GeneXpert MTB/RIF assay to detect pulmonary and extrapulmonary tuberculosis and evaluate the performance for detecting of rifampicin resistance. Of 37,695 samples, 7156 (18.98%) were tuberculosis-positive, and 509 (7.11%) were rifampicin-resistant. The sensitivity, specificity, positive predictive value, negative predictive value, disease prevalence, and accuracy of the GeneXpert MTB/RIF assay for pulmonary tuberculosis were 99.87% (95%CI: 99.75–99.94), 99.92% (95%CI: 99.88–99.95), 99.71% (95%CI: 99.54–99.82), 99.97% (95%CI: 99.93–99.98), 21.38% (95%CI: 20.92–21.86), and 99.91% (95%CI: 99.87–99.94), respectively. For extrapulmonary tuberculosis, the sensitivity, specificity, PPV, NPV, disease prevalence, and accuracy of GeneXpert MTB/RIF assay accounted for 99.45% (95%CI: 98.73–99.82), 99.84% (95%CI: 99.73–99.92), 98.70% (95%CI: 97.73–99.25), 99.93% (95%CI: 99.84–99.97), 10.64% (95%CI: 9.99–11.31), and 99.80% (95%CI: 99.68–99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, GeneXpert MTB/RIF had contradictory results for 20.5% of cases among patients with smear-negative results and 54.9% of cases among patients with a high risk of multidrug-resistant tuberculosis. Of 46% fluoroquinolone-resistant cases, 16.56% (26/157) were multidrug-resistant tuberculosis isolates, and 4.02% (20/498) were isoniazid-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone-resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

Clinical profile of multi-drug reisitance tuberculosis in adults

on 24 march 1884 etiological agent of tuberculosis was discovered by German doctor Dr. Robert Koch, this discovery led to variety of medical applications in diagnosis and management of pulmonary TB. Among many infectious disease prevalent in India, drug resistant TB is one among the important public health problem. There are many factor which influence occurrences of the drug resistant TB, our study conducted mainly to understand those factors which influences the drug resistant TB i.e clinical profile of drug resistant TB in tertiary hospital VIMS, Ballari. The prospective study was conducted in patients admitted in medical college hospitals affiliated to Vijayanagar Institute of Medical Sciences, Ballari over a period of 2 years from November 2016 to October 2018. All patients with sputum AFB and X-ray suggestive of tuberculosis were sent to CBNAAT (Cartridge-based nucleic acid amplification test) for detection of drug resistance. Clinical and radiological characteristics, and risk factors were recorded and further analysis was made. Out of 150 patients with pulmonary tuberculosis 28 of them were detected with drug resistance tuberculosis. Out of 28 drug resistance tuberculosis patients all 28 patients had resistance to isoniazid and rifampicin (MDR-TB). During the study period, among the drug resistant tuberculosis patients the maximum patients belonged to age group 35 to 48yrs of age and males (n=24, 85.7%) outnumbered females (n=4, 14.3%). Fever (n=26, 92.9%) was common symptom. And next common symptom was cough (n=25, 89.2%), loss of appetite, shortness of breath, hemoptysis, loss of weight, chest pain and wheezing. HIV (39.2%) was the common comorbidities among the study patients, followed by diabetes mellitus (35.7%), HTN (35.7%) and COPD (28.5%). About 71.5% of the cases were smokers and 64.3% had history of alcohol consumption and 14.2% were tobacco chewers in this study. About 57.1 % (n=16) were taken ATT previously and not completed treatment and 4 of them were relapse case. This study had shown that, drug resistance tuberculosis is more common than a rare entity and also shows that drug residence is associated with HIV and drug defaulter. Appropriate adherence with ATT and early diagnosis is main determinant in drug resistance TB.