MDR-TB Treatment Research Articles

Experience of Using Delamanid in the Treatment of Multiple Drug Resistant Tuberculosis

The objective: to evaluate treatment results in MDR TB patients when delamanid is added to the treatment regimen.Subjects and Methods. 91 patients with multiple drug resistant pulmonary tuberculosis were included in the study, of which 36 people (39.6%) were HIV positive. Patients were divided into four comparison groups depending on HIV status and inclusion of delamanid in the treatment regimen. Groups receiving delamanid included only patients in whom bedaquiline or linezolid had been discontinued due to adverse reactions.Results. The results of treatment of MDR TB when delamanid is added to the chemotherapy regimen during the intensive phase, indicate its high effectiveness and safety including HIV positive patients.

Prevalence, treatment, and outcomes of hepatitis C in an MDR/RR-TB trial cohort.

Tuberculosis (TB) and chronic hepatitis C virus infection (HCV) remain significant global health challenges, especially in low- and middle-income countries. In Eastern Europe, a considerable percentage of multi-drug resistant (MDR) and rifampicin resistant (RR) TB populations show high HCV prevalence. Current WHO guidelines do not routinely advise HCV testing during MDR-TB treatment, despite HCV being a risk factor for drug-induced liver complications in TB patients. This study investigates the co-treatment of MDR/RR-TB and HCV, using data from the TB-PRACTECAL trial. Data were collected as part of the TB-PRACTECAL clinical trial. All participants were screened for HCV at baseline. Participants who were HCV antibody positive and those who were treated for hepatitis C with Direct Acting Antivirals (DAAs) were extracted and compared to overall cohort characteristics. The characteristics of participants concomitantly treated with direct-acting antivirals are described including hepatitis treatment outcomes and adverse events. Among 552 participants from Belarus, Uzbekistan, and South Africa, 24 (4.3%) were HCV antibody positive. Unfavourable TB treatment outcomes were noted in 106/523 (22%) of the HCV-negative, 8/18 (44%) of the HCV-seropositive, and 2/7 (29%) of HCV-confirmed participants treated with DAAs. Of the six participants who received concurrent HCV and MDR/RR TB treatment, three were cured of HCV and three had no post-treatment HCV RNA test, five completed TB treatment and one discontinued treatment due to a severe adverse reaction. Concurrent treatment of MDR-TB and HCV, including in HIV patients, showed promising outcomes with no significant adverse events. The findings support the potential benefits of integrating HCV care into MDR-TB management.

Immediate Outcomes of Surgical Treatment for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

Objective: To study and compare surgical risks and immediate effectiveness of surgical treatment in patients with multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB).Materials and methods: We examined immediate treatment outcomes of 1180 patients who underwent surgery for destructive MDRTB, pre-XDR-TB, and XDR-TB between 2011 and 2023. The patients were grouped: group 1 for patients with MDR-TB (744 cases) and group 2 for patients with pre-XDR-TB and XDR-TB (436 cases). Moreover, patients were further subdivided based on the extent of surgery.Results: The complete clinical response, ie, cavity closure and elimination of bacilli (CV-, MBT-), was achieved in all 405 patients who underwent radical surgery, in 673 (97.1%) of 694 patients who underwent semiradical surgery, and only in 10 (12.3%) of 81 patients who underwent palliative surgery.Conclusions: The immediate outcomes of surgical treatment for MDR-TB were superior in all parameters compared with those for pre-XDR-TB and XDR-TB; however, we found no significant differences when we evaluated treatment effectiveness in patients who underwent radical and semiradical surgery.

Effectiveness of bedaquiline containing all oral longer regimens in treating multidrug/rifampicin resistant tuberculosis in Pakistan

BackgroundDespite the introduction of bedaquiline (Bdq) containing all-oral regimens for treating patients with rifampicin resistant/multidrug resistant tuberculosis (MDR/RR-TB) in 2019, data on its effectiveness in Pakistan, which has the fifth highest MDR-TB burden, is lacking. This study evaluates treatment outcomes and identifies factors associated with unsuccessful outcomes among MDR/RR-TB patients treated with an all-oral longer treatment regimen (LTR). MethodsThis retrospective record review included all microbiologically confirmed pulmonary MDR/RR-TB patients treated with an all-oral LTR between August 2019 and February 2021 across nine PMDT centres in Pakistan. Sociodemographic and clinical data were retrieved from the Electronic Nominal Recording and Reporting System. Treatment outcomes, defined by WHO criteria, were analysed using SPSS and multivariate binary logistic regression to identify factors associated with unsuccessful outcomes. A p-value < 0.05 was considered statistically significant. ResultsThe final analysis included 644 MDR/RR-TB patients (mean age 37.9 ± 17.6 years), mostly male (53.0 %), underweight (68.0 %), with TB treatment history (66.1 %), MDR-TB (84.9 %), lung cavitation (71.0 %), and no comorbidities (86.4 %). Fluoroquinolone resistance was found in 41.9 %, 16 % had used second-line drugs, and 9.8 % had previous MDR-TB treatment. A total of 400 (62.1 %) patients were declared cured, 53 (8.2 %) treatment completed, 117 (18.2 %) died, 37 (5.7 %) lost to follow-up (LTFU), and 37 (5.7 %) treatment failures. Overall treatment success rate was 70.3 % (n = 453). In multivariate analysis, history of TB treatment (OR:1.63, 95 %CI:1.09–2.64, p = 0.023), previous SLD use (OR:2.09, 95 %CI: 1.20–3.37, p = 0.012), resistance to Z (OR:0.43, 95 %CI: 0.20–0.81, p = 0.023), and resistance to > 5 drugs (OR:3.12, 95 %CI:1.36–11.64, p = 0.013) were significantly associated with death and treatment failure. Whereas, lung cavitation had statistically significant association with LTFU (OR:2.66, 95 %CI:1.10–7.32, p = 0.045). ConclusionTreatment success rate (70.3 %) in this study fell below the WHO recommended target success rate (>90 %). Enhanced clinical management, coupled with special attention to patients exhibiting identified risk factors could improve treatment outcomes.

Results of Treatment of Patients with Multiple Drug Resistant Tuberculosis among Key Populations during the COVID-19 Pandemic in Dushanbe, Tajikistan

The objective: to identify changes in effectiveness of treatment of multiple drug resistant tuberculosis among key populations in Dushanbe, including the period of the COVID-19 pandemic.Subjects and Methods. Retrospective study of medical records of 431 MDR TB patients registered for treatment in Dushanbe was conducted (2017-2019 - Group 1 and 2020-2021 - Group 2 (the COVID-19 pandemic period)).Results. The duration of treatment was 15.4±6.9 months in Group 1, and 10.8±4.3 months in Group 2, which was due to the introduction of short-course regimens in that group. At the same time, in Group 2 there was an increase in effectiveness of MDR TB treatment to 85% versus 80% in Group 1, which was due to the use of new drugs and regimens containing them. In Group 1, a statistically significant association was found between MDR TB treatment failure and the following parameters: male gender (RR=2.3 (1.36-4.04), p=0.002), positive HIV status (RR=2.35 (1.37-4.05), p=0.011), hepatitis C infection (RR=3.0 (1.87-4.8), p &lt;0.001), alcohol (RR=3.2 (1.96-5.2), p&lt;0.001) and substances abuse (RR=3.99 (2.5-6.2), p&lt;0.001), previous imprisonment (RR=2.6 (1.48-4.6), p&lt;0.001), unemployment (RR=3.5 (1.8-6.7), p &lt;0.001), and homelessness (RR=5.0 (3.9-6.5), p=0.0011). In Group 2, failure of MDR TB treatment was statistically significantly associated with hepatitis C (RR=3.3 (1.5-7.2), p=0.02), alcohol and drug abuse (RR= 4.4 ( 1.95-10.1). p =0.026), as well as (unlike Group 1) labor migration (RR=3.0 (1.45-6.2), p=0.0068), in-patient treatment (RR=3.8 (1.36-10.64), p=0.0056), while there was no association with HIV status.

Timing and predictors of death during treatment in patients with multidrug/rifampin-resistant tuberculosis in South Korea.

This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51-358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32-366 d), which was significantly earlier than the median of 184 days (IQR 68-356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75-213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.

Detection of &lt;i&gt;M. tuberculosis&lt;/i&gt; Using Cartridge-Based Technology in Patients with Negative Sputum Microscopy Results in a Regional Laboratory

The objective: to evaluate results of M. tuberculosis detection and testing drug susceptibility to rifampicin using molecular genetic methods in tuberculosis patients with a negative sputum smear microscopy result.Subjects and Methods. Pulmonary tuberculosis patients registered in Arkhangelsk Region from 2016 to 2020 were enrolled in the study; those patients were notified as new cases and relapses with a negative sputum smear microscopy result before treatment and had results of molecular genetic testing (MGT) (Xpert MTB/RIF MTB/RIF) and BACTEC MGIT 960 available.Results. 479 people (40%) were registered as pulmonary tuberculosis cases with a negative sputum smear microscopy result. MGT was performed in 327 (68%) patients. A positive result of MGT was received in 120 (37%) patients, a positive result of BACTEC MGIT 960 was received in 165 (50%) people. Concordance of results was observed in 70% of cases. In 136 (41%) people, both tests did not detect Mycobacterium tuberculosis, in 95 (29%) both tests showed a positive result. Discrepancies between the results of two tests were observed in 30% of cases. In 71 (22%) cases, culture growth was observed in BACTEC MGIT 960 with negative results of MGT. In 8% of cases, DNA of Mycobacterium tuberculosis was detected, but there was no culture growth on the nutrient medium. 43/120 (36%) cases of resistance to rifampicin were detected. The median time from sputum collection to initiation of MDR-TB treatment based on sputum MGT results made 18 (IQR 10–29) days. Molecular genetic testing makes it possible to promptly detect the majority of TB patients with a negative sputum smear result, and reduce the time for drug susceptibility testing, which allows this testing to be used as the first test when examining for pulmonary TB.

A pragmatic randomized controlled trial to evaluate the efficacy and safety of an oral short-course regimen including bedaquiline for the treatment of patients with multidrug-resistant tuberculosis in China: study protocol for PROSPECT

IntroductionThe lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China.MethodsThis phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18–65 years) in China. The trial design mainly mirrors that of the “Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB” (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority.DiscussionPROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16.Trial registrationClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.

FOLLOW-UP CASES OF BEDAQUILINE IN XDR-TB PATIENTS: A CASE SERIES

Tuberculosis has consistently maintained its lead position in being among the top 10 causes by means of single-cause etiology for death among infectious disease patients. On top of it, now multi-drug resistant cases of tuberculosis (MDR-TB) are raising concern. The vision of tuberculosis eradication gets a major setback with a total of 206,030 million cases being reported worldwide with MDR or rifampicin-resistance MDR-TB in 2019. Bedaquilline a relative recent drug is being made available for the treatment of MDR and extensive drug resistance (XDR) TB under NTEP. It is being provided as a part of 2nd line of drug therapy. Regarding the drug’s efficacy and safety profiling Bedaquiline has been under extensive clinical trials at medical institutes and hospitals of reputation at national level. The treatment options available to treat XDR-TB remain extremely limited at the cost of being less effective, expensive and with more side effects. Even after the availability of potent anti-tubercular drugs, XDR Tuberculosis is proving to be more resistant to all possible drugs available to work against it.

Financial burden of tuberculosis diagnosis and treatment for patients in Ethiopia: a systematic review and meta-analysis

BackgroundDespite the diagnosis and treatment of tuberculosis (TB) given free of charge in many high-burden countries, the costs that patients face in the cascade of care remain a major concern. Here, we aimed to investigate the financial burden of TB diagnosis and treatment for people with TB in Ethiopia.MethodFor this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Cochrane Center for Clinical Trials from December 1 2022 to 31 June 2023 for articles reporting the cost of diagnosis and treatment for patients regardless of their age with all forms of TB in Ethiopia. Major study outcomes were catastrophic costs, direct (out-of-pocket) pre-diagnosis, medical cost, and post-diagnosis costs, indirect (income loss) costs, coping costs, and total costs. We have used a threshold of 20% to define catastrophic costs. We used random-effects meta-analyses to calculate summary estimates of costs. R-studio software was used for analysis. The study is registered with PROSPERO: CRD42023387687.ResultTwelve studies, with a total of 4792 patients with TB, were included in our analysis. At the 20% threshold of total expenses, 51% of patients (2301 participants from 5 studies, 95% CI: 36-65%, I2 = 97%) faced catastrophic costs due to bacteriologically confirmed drug-sensitive pulmonary TB. Private facility diagnosis, drug-resistance TB, TB-HIV co-infection, hospitalization, and occupation were found to be associated with catastrophic costs. Reduction in the total cost spent by the patients was associated with digital adherence interventions, community-based direct observed therapy, short-course MDR-TB treatment regimens, and active case-finding. Pre-diagnosis costs had a positive correlation with diagnosis delays and the number of facilities visited until diagnosis. Post-diagnosis costs had a positive correlation with rural residence and inpatient treatments.ConclusionIrrespective of a national policy of free TB service, more than half of TB patients are suffering catastrophic costs due to drug-sensitive pulmonary TB in Ethiopia and most of the patients spend a lot of money during the pre-diagnosis period and intensive phase, but declined drastically over time. Active case-finding, digital adherence interventions, community-based treatment, and comprehensive health insurance coverage have the potential to minimize the financial burden of TB diagnosis and treatment.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda

BackgroundMixed M. tuberculosis (MTB) infection occurs when one is infected with more than one clonally distinct MTB strain. This form of infection can assist MTB strains to acquire additional mutations, facilitate the spread of drug-resistant strains, and boost the rate of treatment failure. Hence, the presence of mixed MTB infection could affect the performance of some rapid molecular diagnostic tests such as Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays.MethodsThis was a cross-sectional study that used sputum specimens collected from participants screened for STREAM 2 clinical trial between October 2017 and October 2019. Samples from 62 MTB smear-positive patients and rifampicin-resistant patients from peripheral health facilities were processed for Xpert and LPA as screening tests for eligibility in the trial. From November 2020, processed stored sputum samples were retrieved and genotyped to determine the presence of mixed-MTB strain infection using a standard 24-locus Mycobacterial Interspersed Repetitive Unit–Variable Number Tandem-Repeat (MIRU-VNTR). Samples with at least 20/24 MIRU-VNTR loci amplified were considered for analysis. Agar proportional Drug Susceptibility Test (DST) was performed on culture isolates of samples that had discordant results between LPA and Xpert. The impact of the presence of mixed-MTB strain on Xpert and LPA test interpretation was analyzed.ResultsA total of 53/62 (85%) samples had analyzable results from MIRU-VNTR. The overall prevalence of mixed-MTB infection was 5/53 (9.4%). The prevalence was highest among male’s 3/31 (9.7%) and among middle-aged adults, 4/30 (33.3%). Lineage 4 of MTB contributed 3/5 (60.0%) of the mixed-MTB infection prevalence. Having mixed MTB strain infection increased the odds of false susceptible Xpert test results (OR 7.556, 95% CI 0.88–64.44) but not for LPA. Being HIV-positive (P = 0.04) independently predicted the presence of mixed MTB infection.ConclusionsThe presence of mixed-MTB strain infection may affect the performance of the GeneXpert test but not for LPA. For patients with high pre-test probability of rifampicin resistance, an alternative rapid method such as LPA should be considered.

Analiza ishoda lečenja multirezistentne tuberkuloze - iskustvo u Specijalnoj bolnici za plućne bolesti "Ozren" - Sokobanja

Multidrug-resistant tuberculosis (MDR TB) is currently considered to be the most significant and dangerous obstacle to the TB elimination, and the work on preventing this form of disease is considered as a major contribution to human health and resource management. The purpose of the article is to analyse treatment outcomes in patients treated for multiresistant tuberculosis at the Special Hospital for Pulmonary Diseases "Ozren" - Sokobanja in the period from 2009 to 2019 and identify factors associated with treatment outcomes. We performed a retrospective analysis of the treatment outcomes in all (n=89) cases of MDR TB treated over the period from 2009-2019 at the Special Hospital for Pulmonary Diseases Ozren - Sokobanja. Descriptive statistical analysis of all available MDR TB characteristics was used. Logistic regression analysis was used to identify factors associated with successful treatment (treatment outcomes "cured" and "treatment completed") and mortality. Patient mortality was statistically significantly associated with undernutrition (OR = 5.55; 95% CI: 1.39-20.00), alcohol consumption (OR = 4.54; 95% CI: 1.22-10.67), bilateral cavitary lesions (OR = 16.67; 95% CI: 3.03-100.00), multiple prior treatment episodes (p&lt;0.001), longer time to diagnosis (p&lt;0.001), higher average number of hospitalizations and previous treatment episodes (p&lt;0.001), and the following comorbidities: pulmonary (OR = 14.29; 95% CI: 2.70-100.00), cardiovascular diseases (OR = 7.14; 95% CI: 1.79-25.00), diabetes (OR = 5.88; 95% CI: 1.39-25.00) and malignant diseases (OR = 12.50; 95% CI: 1.85-100.00). The success of MDR TB treatment is very good. To maintain and further improve this success, it is necessary to focus interventions on resolving social issues and comorbidities among patients from risk groups associated with poor treatment outcomes, as well as on education of health professionals related to suspicion of TB, its recognition and referral to specialized institutions for MDR TB diagnostics and treatment.

TREATMENT OF ACTIVE AND LATENT MULTIDRUG-RESISTANT TUBERCULOSIS IN CHILDREN OF THE SAME FAMILY

An observation of the management of active and latent tuberculosis with multidrug resistance of the causative agent of the disease in children from the same family has been presented. The efficacy and safety of a short, fully oral chemotherapy regimen with the use of new and repurposed drugs in a child with active pulmonary tuberculosis has been demonstrated. During the preventive treatment of latent tuberculosis infection for six months no adverse reactions after taking levofloxacin were reported. In one case, preventive treatment of latent MDR-TB was not carried out due to co-pathology newly diagnosed before taking the drug.

Adverse Drug Reactions in Multi-Drug Resistant Tuberculosis Patients, in India, who had received DOTS Plus Treatment along with Home Care and Counselling

Background: Adverse drug reactions are common in MDR-TB patients on treatment. An adverse drug reaction (ADR) is defined as an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product. Revised National Tuberculosis Control Programme used 24-months long Category IV/DOTS Plus regimen for treatment of MDR-TB. The Community Health Department of St. Stephen’s Hospital started an innovative project in 2009, in the form of Home Care for MDR Patients and it concluded with Long-term Follow-up of patients, who had received DOTS Plus Treatment along with Home Care and Counselling (2015). Aims: To study the spectrum, severity and the risk factors for ADRs in MDR-TB patients. Methods: In this retrospective study files of 109 MDR-TB patients who had received treatment along with home care and counselling support, were reviewed. The study was conducted between January to May 2024. Results: Out of 109 MDR TB patients there were 68 (62%) developed one or more ADR. Joint pains 44(40.36%), was the most commonly observed ADR, followed by nausea 29(26.6%) and vomiting 25(22.93%), weakness 23(21.1%), anxiety and depression 16(14.67%), difficulty in breathing 14(12.84%), tremors 13(11.9%), giddiness 11(10.1%), skin rashes 10(9.2%). According to Hartwig Scale mild ADRs were 58.8%, moderate 5.9% and severe 35.3%. Patients who had BMI &lt;18.5 experienced less ADRs with an Odds Ratio =0.22; 95% CI=0.06 to 0.72, p=0.0124. Unemployment was associated with higher number of ADRs OR=3.5; 95% CI=0.99 to 12.29, p=0.05. Sixty-two % MDR TB patients had ADRs. Our treatment outcomes showed 41(60.3) as cured, 24(35.3) died, 2(2.9) defaulted and 1(1.5) failed treatment. This was possible because healthcare teams counselled and provided all possible support to patients 24x7 thus improving adherence to therapy. Conclusion: ADRs occurred in more than half of the cases, with joint pain being the most common. Interventions such as counselling of patients and their family on importance of adherence to drugs at the initiation of treatment, provision of nutritional support, psychological counselling and motivation, instant referral for ADRs and care of patients at referred facilities, help patients not becoming defaulters.

Pulmonary Thromboembolism in Multidrug-Resistant Tuberculosis: A Case Series Highlighting the Importance of Early Diagnosis and Management

Background: Pulmonary tuberculosis (PTB) is an established cause of arterial and venous thrombosis. With the rising incidence of multidrug-resistant tuberculosis (MDR TB), which has a prolonged treatment course, pulmonary thromboembolism in such cases further complicates the treatment outcome in terms of mortality and morbidity. TB causes systemic hypercoagulability, which may lead to both arterial and venous thrombosis. Therefore, it is important for treating physicians to be aware of the entity and have a sharp watch for the development of Pulmonary thromboembolism in cases of MDR TB. The Case: We present the association of pulmonary thromboembolism (PTE) with MDR TB in three young males who developed pulmonary thromboembolism during the treatment of MDR TB, along with their management using anticoagulant agents. Conclusion: PTE in cases of TB is rare but fatal. High suspicion of PTE in patients with MDR TB will help in diagnosing the dreaded condition early and aid in reducing preventable mortality with PTE. Early recognition, prompt diagnosis, and management is the key to saving the lives of those with this fatal complication.

Screening with GenoType® MTBDRplus shortens the time to MDR-TB treatment initiation but does not change outcomes.

Screening with GenoType® MTBDRplus shortens the time to MDR-TB treatment initiation but does not change outcomes.

Tuberculosis multirresistente en Colombia, 2013-2018: estudio de casos y controles

Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult to control, has high morbidity and mortality, and demands priority public health intervention. In Colombia, MDR/RR-TB has been becoming more widespread annually. Before the COVID-19 pandemic, over an 8-year period, the number of cases of multidrug-resistant tuberculosis in Colombia was close to a thousand cases. Timely identification of the different risk factors for MDR/RR-TB will contribute fundamentally to the systematic management. To determine which risk factors were associated with the presentation of MDR in Colombia between 2013 and 2018. A retrospective case-control study was carried out, for which the data from the routine surveillance of MDR/events in the country were used. The cases of multidrug-resistant tuberculosis were mainly in young people, Afrodescendants, and males. Of the clinical conditions, comorbidities such as malnutrition, diabetes, and HIV, presence of at least one factor, such as drug dependence, taking immunosuppressive medications, belonging to the black race, afro, and living in an area of high disease burden were risk factors. In addition to the diagnosis and timely provision of MDR-TB treatment, it is necessary that public health programs at the local level pay special attention to patients with the identified risk factors.

Treatment of MDR, pre-XDR, XDR and rifampicin resistant tuberculosis or in case of intolerance to at least rifampicin in Austria, Germany and Switzerland - Amendment dated 19.09.2023 to the Sk2-Guideline: Tuberculosis in adulthood of the German Central Committee against Tuberculosis (DZK) on behalf of the German Respiratory Society (DGP)

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'.

Investigation of genomic mutations and their association with phenotypic resistance to new and repurposed drugs in Mycobacterium tuberculosis complex clinical isolates.

WGS has the potential to detect resistance-associated mutations and guide treatment of MDR TB. However, the knowledge base to confidently interpret mutations associated with the new and repurposed drugs is sparse, and phenotypic drug susceptibility testing is required to detect resistance. We screened 900 Mycobacterium tuberculosis complex genomes from Ireland, a low TB incidence country, for mutations in 13 candidate genes and assessed their association with phenotypic resistance to bedaquiline, clofazimine, linezolid, delamanid and pretomanid. We identified a large diversity of mutations in the candidate genes of 195 clinical isolates, with very few isolates associated with phenotypic resistance to bedaquiline (n = 4), delamanid (n = 4) and pretomanid (n = 2). We identified bedaquiline resistance among two drug-susceptible TB isolates that harboured mutations in Rv0678. Bedaquiline resistance was also identified in two MDR-TB isolates harbouring Met146Thr in Rv0678, which dated back to 2007, prior to the introduction of bedaquiline. High-level delamanid resistance was observed in two isolates with deletions in ddn, which were also resistant to pretomanid. Delamanid resistance was detected in two further isolates that harboured mutations in fbiA, but did not show cross-resistance to pretomanid. All isolates were susceptible to linezolid and clofazimine, and no mutations found were associated with resistance. More studies that correlate genotypic and phenotypic drug susceptibility data are needed to increase the knowledge base of mutations associated with resistance, in particular for pretomanid. Overall, this study contributes to the development of future mutation catalogues for M. tuberculosis complex isolates.

THE EFFECTIVENESS AND SAFETY OF BEDAQUILINE-CONTAINING REGIMENS IN THE TREATMENT OF PATIENTS WITH MULTI-DRUG RESISTANT TUBERCULOSIS (MDR-TB): A SYSTEMATIC LITERATURE REVIEW

Objective: MDR-TB is a life-threatening infectious disease. In recent years, RR/MDR TB sufferers have increased by 10% from 186,883 patients in 2018 to 206,030 in 2019. The success rate of treatment for RR/MDR-TB patients only reaches 57% globally. WHO has recommended bedaquiline for treatment of MDR-TB as the first drug in an all-oral regimen designed to maximize treatment outcomes. Purpose: to describe the efficacy and safety of a bedaquiline-containing regimen for the treatment of MDR-TB. Methods: Pubmed, Science Direct, and Embase online databases were used to obtain data published in the last five years where literature searches were carried out independently by researchers. The keywords used in this search are combined with the Boolean operator "AND", namely (bedaquiline) AND (multidrug resistant) AND (effectiveness). Results: Eight studies met the inclusion criteria, demonstrating a higher conversion rate of sputum cultures on the bedaquiline containing regimen between 74%-95.8% with a mean time to culture conversion between 39 days-3 months. The majority of studies reported an adverse effect of QT prolongation in patients treated with bedaquiline. Conclusion: This systematic review showed that bedaquiline is effective and safe for use in the treatment of MDR-TB. However, serious side effects of QT prolongation occurred in some respondents who were treated with bedaquiline, so an effective and efficient monitoring and surveillance system is needed to ensure best practice in the treatment of MDR-TB.