Bioassay-guided isolation and structure elucidation of anti-mycobacterium tuberculosis compounds from Galatella grimmii (Regel & Schmalh.) Sennikov.

BACKGROUND: Galatella is a genus in the family Asteraceae, represented by 35-45 species. Considering the high effectiveness of the ethyl acetate (EtOAc) fraction of G. grimmii against Mycobacterium tuberculosis (MIC = 0.5 µg/mL), a bioassay-directed fractionation of this extract was carried out. METHODS: The methanolic extract of the aerial parts of G. grimmii was obtained using maceration, then it was suspended in water and partitioned with petroleum ether, dichloromethane (CH2Cl2), EtOAc, and n-butanol (n-BuOH), successively. The most potent fraction (EtOAc), was selected for further isolation by Sephadex LH-20 and semi-preparative HPLC to obtain active compounds. RESULTS: Fractionation of the EtOAc solvent fraction resulted in the characterization of five compounds, among them, compounds 1 and 2 showed the highest anti-mycobacterial effects with MICs of 0.062 and 1.00 µg/mL against H37Rv M. tuberculosis, respectively, which were higher than those of rifampin (MIC of 1.25 µg/mL) and isoniazid (MIC of 0.31 µg/mL), as positive controls. Also, compound 1 ​​inhibited all tested strains of drug-resistant Mycobacterium (MDR and XDR). Notably, the isolated compounds have been reported for the first time from G. grimmii. CONCLUSION: Due to the potent anti-mycobacterial effect of isolated compounds from G. grimmii, this study could pave the way for developing a novel class of natural anti-tuberculosis compounds.

Tuberculosis presenting as Anterior Mediastinal Mass: A Case Report.

ABSTRACT: The mediastinum, located between the pleural sacs, has three compartments. The anterior mediastinum spans anteriorly from the sternum to the pericardium and brachiocephalic vessels posteriorly. Common lesions in this area include thymomas, lymphomas, teratomatous neoplasms, and thyroid masses. A mediastinal mass in the setting of tuberculous meningoencephalitis is an uncommon presentation of tuberculosis. We present a case of a 20-year-old girl with fever and headache diagnosed with tuberculous meningoencephalitis. A thorough workup revealed an anterior mediastinal mass, histopathologically diagnosed as tubercular in origin. Treatment involved surgery and antituberculosis therapy. Tuberculosis can manifest uniquely, and an isolated mediastinal mass, especially in an immunocompetent individual, is unusual. Treatment typically involves a combination of antimicrobial medications, and in some cases, surgical intervention may be necessary to address complications or persistent masses. This case emphasizes the importance of considering tuberculosis as a diagnosis when a patient presents with a mass in the anterior mediastinum.

Crohn's Disease Previously Mistreated as Intestinal Tuberculosis Complicated with Ileocecal Lump: A Case Report.

In Southeast Asia, the higher prevalence of Intestinal tuberculosis (TB) challenges the diagnosis of Crohn's disease (CD) due to their overlapping symptoms. This case involves a 25-year-old male misdiagnosed with Intestinal tuberculosis presenting with abdominal pain, weight loss, and bowel ulceration. Recurrence after anti-tubercular therapy led to further investigation paving to right hemicolectomy and histopathological analysis confirming Crohn's disease. This case highlights the complexity of the diagnosis of Crohn's disease in tuberculosis-prevalent areas, stressing the clinical importance, advanced diagnostics tools, and multidisciplinary approach for effective intervention.

Efficacy and safety of shorter multidrug-resistant or rifampicin-resistant tuberculosis regimens: a network meta-analysis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens. METHODS: We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050). RESULT: We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care. CONCLUSION: Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.

Unveiling the complexity of rifampicin drug susceptibility testing in Mycobacterium tuberculosis: comparative analysis with next-generation sequencing.

Introduction. The discordance between phenotypic and molecular methods of rifampicin (RIF) drug susceptibility testing (DST) in Mycobacterium tuberculosis poses a significant challenge, potentially resulting in misdiagnosis and inappropriate treatment.Hypothesis/gap statement. A comparison of RIF phenotypic and molecular methods for DST, including whole genome sequencing (WGS), may provide a better understanding of resistance mechanisms.Aim. This study aims to compare RIF DST in M. tuberculosis using two phenotypic and molecular methods including the GeneXpert RIF Assay (GX) and WGS for better understanding.Methodology. The study evaluated two phenotypic liquid medium methods [Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT)], one targeted molecular method (GX), and one WGS method. Moreover, mutational frequency in ponA1 and ponA2 was also screened in the current and previous RIF resistance M. tuberculosis genomic isolates to find their compensatory role.Results. A total of 25 RIF-resistant isolates, including nine from treatment failures and relapse cases with both discordant and concordant DST results on LJ, MGIT and GX, were subjected to WGS. The phenotypic DST results indicated that 11 isolates (44%) were susceptible on LJ and MGIT but resistant on GX. These isolates exhibited multiple mutations in rpoB, including Thr444>Ala, Leu430>Pro, Leu430>Arg, Asp435>Gly, His445>Asn and Asn438>Lys. Conversely, four isolates that were susceptible on GX and MGIT but resistant on LJ were wild type for rpoB in WGS. However, these isolates possessed several novel mutations in the PonA1 gene, including a 10 nt insertion and two nonsynonymous mutations (Ala394>Ser, Pro631>Ser), as well as one nonsynonymous mutation (Pro780>Arg) in PonA2. The discordance rate of RIF DST is higher on MGIT than on LJ and GX when compared to WGS. These discordances in the Delhi/CAS lineages were primarily associated with failure and relapse cases.Conclusion. The WGS of RIF resistance is relatively expensive, but it may be considered for isolates with discordant DST results on MGIT, LJ and GX to ensure accurate diagnosis and appropriate treatment options.

LATENT TUBERCULOSIS IN PATIENTS WITH CROHN'S DISEASE IN A UNIVERSITY HOSPITAL IN NORTHEASTERN BRAZIL: A RETROSPECTIVE STUDY.

BACKGROUND: Among chronic condition problems, tuberculosis still represents a serious public health problem globally. OBJECTIVE: To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis. METHODS: The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. RESULTS: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. CONCLUSION: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.

EFFICACY AND SAFETY OF SILVER NANOCOMPOSITES ON RIFAMPICIN-RESISTANT M. TUBERCULOSIS STRAINS.

BACKGROUND: Control of rifampicin-resistant tuberculosis (RR-MTB) requires novel technologies for restoring the anti-TB efficacy of priority drugs. We sought to evaluate the ability of nanotechnology application in the recovery of the anti-tuberculosis efficacy of rifampicin. METHODS: Nanocomposite- standard dose of rifampicin and 20 nm silver nanoparticles (AgNPs) suspension solution of 6 different concentrations: 0.25%; 0.5%; 1%; 2.5%; 5%; and 10%, were supplemented to 70 rifampicin-resistant mycobacterium tuberculosis (RR-MTB) isolates. The control arm consisted of 35 RR-MTB isolates and AgNPs suspension with identical concentrations. The inhibitory effect of nanocomposites was evaluated by MTB growth rate using the BACTECTM MGIT 960TM. The safety assessment of single-use AgNPs was conducted in experimental animals. RESULTS: The suppression process of AgNPs on RR-MTB isolates started with 2,5% nanocomposite solution application and full suppression was achieved in 5% and 10% nanocomposite solutions. A standard dose of rifampicin and a 2.5% solution of AgNPs increased the minimal inhibitory effect on RR-MTB by 10% (total 80%) vs the isolated use of a 2.5% solution of AgNPs (70%). An experiment on animals revealed the complete safety of a single injection of ultra-high doses of AgNPs. CONCLUSION: The study showed the potentiating effect of AgNPs in overcoming the resistance of MTB to rifampicin providing a scientific basis for further research.

Challenging the Biginelli scaffold to surpass the first line antitubercular drugs: Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibition activity and molecular modelling studies.

New Biginelli adducts were rationalised, via the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natural substrate of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt). Repurposing was one of the design rationale strategies for some selected mimics of the designed compounds. The anti-TB activity was screened against the Mtb H37Rv strain where 11a was superior to ethambutol (EMB), and was 9-fold more potent than pyrazinamide (PZA). Additionally, compounds 11b, 4a, 4b, 13a, 13b and 14a elicited higher anti-TB activity than PZA, showing better safety profiles than EMB against RAW 264.7 cells' growth. The in vitro TMPKmt inhibition assay released compounds 11a, 11b and 13b as the most potent inhibitors. Docking studies presumed the binding modes and molecular dynamics (MD) simulation revealed the dynamic stability of 11a-TMPKmt complex over 100 ns. In silico prediction of the chemo-informatics properties of the most active compounds was conducted.

A decline in tuberculosis diagnosis, treatment initiation and success during the COVID-19 pandemic, using routine health data in Cape Town, South Africa.

BACKGROUND: Coronavirus disease (COVID-19) negatively impacted tuberculosis (TB) programs which were already struggling to meet End-TB targets globally. We aimed to quantify and compare diagnosis, treatment initiation, treatment success, and losses along this TB care cascade for drug-susceptible TB in Cape Town, South Africa, prior to and during COVID-19. METHODS: This observational study used routine TB data within two predefined cohorts: pre-COVID-19 (1 October 2018-30 September 2019) and during-COVID-19 (1 April 2020-31 March 2021). The numbers of people diagnosed, treated for TB and successfully treated were received from the Western Cape Provincial Health Data Centre. Pre and post treatment loss to follow up and cascade success rates (proportion of individuals diagnosed with an outcome of treatment success) were calculated and compared across cohorts, disaggregated by sex, age, HIV status, TB treatment history and mode of diagnosis. RESULTS: There were 27,481 and 19,800 individuals diagnosed with drug-susceptible TB in the pre- and during-COVID-19 cohorts respectively, a relative reduction of 28% (95% CI [27.4% - 28.5%]). Initial loss to follow up increased from 13.4% to 15.2% (p<0.001), while post treatment loss increased from 25.2% to 26.1% (p < 0.033). The overall cascade success rate dropped by 2.1%, from 64.8% to 62.7% (p< 0.001). Pre- and during-COVID-19 cascade success rates were negatively associated with living with HIV and having recurrent TB. CONCLUSIONS: An already poorly performing TB program in Cape Town was negatively impacted by the COVID-19 pandemic. There was a substantial reduction in the number of individuals diagnosed with drug-susceptible. Increases in pre-and post-treatment losses resulted in a decline in TB cascade success rates. Strengthened implementation of TB recovery plans is vital, as health services now face an even greater gap between achievements and targets and will need to become more resilient to possible future public health disruptions.

Tuberculosis patients' satisfaction with directly observed treatment short course strategy and associated factors in Southern Ethiopia: a mixed method study.

BACKGROUND: Tuberculosis (TB) is a second major global public health problem and the leading infectious cause of death in Ethiopia. Patients under directly observed treatment short-courses (DOTs) have a higher treatment success rate and reduced drug resistance. A successful treatment outcome and adherence to the treatment are related to patient satisfaction with the DOT strategy. Client satisfaction is one of the indicators of the quality of care. In this perspective, there were limited studies in Ethiopia related to patient satisfaction with the DOTs strategy in the prevention and control of TB to achieve the ''END TB Strategy.'' Therefore, this study was aimed at identifying the TB patients' satisfaction with the DOTs strategy and associated factors in Gamo Zone, Southern Ethiopia. METHODS: An institutional-based cross-sectional study design for quantitative data and a phenomenological approach were employed for qualitative data. The calculated sample size was 374. A systematic random sampling method was used to select study participants. A pre-tested structured interviewer-administered questionnaire for quantitative data and focus group discussions (FGDs) for qualitative data were used for data collection. Bivariable and multivariable analyses were used. The determinants with a p-value < 0.05 were declared to have a significant association with the outcome variable, and an adjusted odd ratio with a 95% confidence interval (CI) was used. RESULTS: A total of 358 patients participated in the study, with a response rate of 95.72%. The majority of study participants' ages ranged between 25 and 34 years. The tuberculosis DOT satisfaction rate was 61.17% [56.10-66.25%, 95%CI]. The TB patients who took treatment for 20 weeks or more were 3.97 times [AOR = 3.97; 95% CI (1.55-10.16)] more likely to be satisfied with the DOTs service provided. However, the participants who perceived transport costs as high were 79% [AOR = 0.21; 95% CI (0.06-0.71)] less likely to be satisfied with DOTs. Qualitatively, the participants reported that there was a major problem with laboratory services, which resulted in delays and long appointments to get the results in addition to lack of clean toilets and safe water to swallow medications. CONCLUSION: The satisfaction rate for tuberculosis DOTs observed in this study appears to be relatively lower in comparison to other studies. Availing DOTs service nearby patients to enhance the accessibility of the service is crucial to improving patients' satisfaction with DOTs service. Reducing laboratory result delays by improving laboratory service is essential to enhancing patients' satisfaction with DOTs. Moreover, improving toilet services, and availing safe water to swallow medications is recommended to enhancing patients' satisfaction with DOTs service.

Dynamic changes of respiratory microbiota associated with treatment outcome in drug-sensitive and drug-resistant pulmonary tuberculosis.

BACKGROUND: Respiratory microbiota is closely related to tuberculosis (TB) initiation and progression. However, the dynamic changes of respiratory microbiota during treatment and its association with TB progression remains unclear. METHODS: A total of 16 healthy individuals and 16 TB patients (10 drug-sensitive TB (DS-TB) and 6 drug-resistant TB (DR-TB)) were recruited. Sputum samples were collected at baseline for all anticipants and after anti-TB treatment at Month-6 for TB patients. High throughput 16 S RNA sequencing was used to characterize the respiratory microbiota composition. RESULTS: Compared to the healthy individuals, TB patients exhibited lower respiratory microbiota diversity (p < 0.05). This disruption was alleviated after anti-TB treatment, especially for DS-TB patients. Parvimonas spp. numbers significantly increased after six months of anti-TB treatment in both DS-TB and DR-TB patients (p < 0.05). Rothia spp. increase during treatment was associated with longer sputum-culture conversion time and worse pulmonary lesion absorption (p < 0.05). Besides, Moraxella spp. prevalence was associated with longer sputum-culture conversion time, while Gemella spp. increase was associated with worsening resolving of pulmonary lesions (p < 0.05). CONCLUSION: Dynamic changes of respiratory microbiota during anti-TB treatment is closely related to TB progression. The involvement of critical microorganisms, such as Parvimonas spp., Rothia spp., Moraxella, and Gemella spp., appears to be associated with pulmonary inflammatory conditions, particularly among DR-TB. These microorganisms could potentially serve as biomarkers or even as targets for therapeutic intervention to enhance the prognosis of tuberculosis patients.

Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

Coexistence of pulmonary thromboembolism and pulmonary tuberculosis: a diagnostic dilemma.

A man in his early 50s with previously treated pulmonary tuberculosis (TB) presented with a 3-month history of cough, expectoration and progressive breathlessness, accompanied by significant weight loss. Examination revealed tachycardia, tachypnoea, hypoxaemia and unilateral diminished breath sounds. Investigations showed anaemia, leucocytosis and a homogeneous opacity on the left side of the CXR. ECG and echocardiography suggested pulmonary thromboembolism (PTE). A CT pulmonary angiogram confirmed a chronic embolus and a severely fibrosed left lung. A comprehensive thrombophilia workup yielded normal results and the PTE was attributed to his history of TB. Sputum analysis confirmed reactivated TB, leading to the initiation of antitubercular therapy. The patient improved clinically with plans for a repeat CT pulmonary angiography to assess the need for pulmonary thromboendarterectomy after completing TB treatment. This case highlights the possible association of TB and PTE, its management and why it should be considered as a differential diagnosis in patients with a history of TB presenting with exacerbated breathlessness.

[Disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation: a case report].

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis. She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.

Smoking cessation to prevent death and tuberculosis recurrence after treatment: A prospective cohort study with a seven-year follow-up in China.

Background: Although there is consistent evidence that smoking is a risk factor associated with tuberculosis (TB), whether smoking cessation improves treatment outcomes and reduces the risk of TB recurrence remains understudied. Methods: We conducted a prospective cohort study with a seven-year follow-up in China. We recruited newly-diagnosed TB patients and classified them as non-smokers, ex-smokers, and current smokers. Current smokers were invited to participate in a smoking cessation intervention programme. We used a Cox proportional hazards model to assess the risk of death among TB patients and the risk of recurrence among successfully treated patients. Results: In total, 634 (79.2%) patients completed anti-TB treatments and 115 (14.4%) patients died. We confirmed the existence of a dose-response relationship between smoking frequency and the risk of TB recurrence (the slope of the fitted line >0; P < 0.05). Compared to those who continued smoking, the risk of death and recurrent TB for the patients who quit smoking during treatment decreased. The HR of mortality for smokers who smoked 30 or more cigarettes was 2.943 (95% confidence interval (CI) = 1.035-8.368), while the HR of mortality for those who smoked 30 or more cigarettes, but quit during treatment was 2.117 (95% CI = 1.157-3.871). However, the risk of recurrence remained high for ex-smokers who had a smoking history of 25 years or more. Conclusions: Our study provides further evidence supporting the World Health Organization's call for co-management of smoking and other risk factors as part of routine TB treatment.

A machine-learning based model for automated recommendation of individualized treatment of rifampicin-resistant tuberculosis.

BACKGROUND: Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. METHODS: We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. RESULTS: Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. CONCLUSIONS: Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of patients with RR-TB, especially those with 'difficult-to-treat' forms of RR-TB.

Treatment for multidrug-resistant tuberculosis: A comparative analysis of programmatic outcome indicators between Buenaventura and other municipalities of Valle del Cauca, Colombia / Tratamiento para tuberculosis resistente a rifampicina o multirresistente: análisis comparativo de indicadores programáticos entre Buenaventura y otros municipios del Valle del Cauca, Colombia

Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.

Introducción. El manejo adecuado de la tuberculosis multirresistente es una estrategia priorizada para el control de la tuberculosis en el mundo. Objetivo. Evaluar las diferencias entre las características demográficas y clínicas, y los indicadores programáticos de los pacientes con diagnóstico confirmado de tuberculosis pulmonar resistente a rifampicina o multirresistente en Buenaventura, frente a la cohorte de los demás municipios del Valle del Cauca entre 2013 y 2016. Materiales y métodos. Se desarrolló un estudio analítico de cohortes para comparar los registros de pacientes mayores de 15 años con tuberculosis multirresistente, del Programa de Tuberculosis de Buenaventura (con ácido paraaminosalicílico), frente a los demás municipios del Valle del Cauca (sin ácido paraaminosalicílico). Resultados. Se registraron 99 casos con una mediana de edad de 40 años (RIC = 26- 53); en Buenaventura, el 56 % eran mujeres; en los demás municipios, predominaron los hombres (67 %); el 95 % de los evaluados tenía aseguramiento en salud. La comorbilidad más frecuente fue diabetes (14 %). Las reacciones adversas a medicamentos antituberculosos en Buenaventura fueron 1,3 veces más frecuentes que en los demás municipios (OR = 2,3; IC95 %: 0,993 - 5,568; p = 0,04). En Buenaventura falleció el 5 % de los casos frente al 15 % reportado en los demás municipios. No hubo fracasos con el tratamiento en Buenaventura, pero se reportó un 35 % de pérdida del seguimiento. El éxito del tratamiento fue mayor en Buenaventura en el 56 %. Conclusión. El programa fortalecido de Buenaventura presentó mejores resultados programáticos que los demás municipios del Valle del Cauca. El acceso a pruebas moleculares, la disponibilidad de tratamientos acortados y el seguimiento continuo para identificar reacciones adversas a medicamentos antituberculosos son un derrotero para todos los programas de control.

Evaluation of mycobacterial microscopy and culture results from clinical samples: A five-year analysis.

Introduction: Ehrlich-Ziehl-Neelsen (EZN) staining and culture methods are often used to diagnose tuberculosis. This study aimed to determine the acidfast bacteria (AFS) positivity rates in various clinical samples sent to our laboratory over five years and the growth and resistance rates in two different (solid and liquid) cultures and compare them with the data from Türkiye and the world. Materials and Methods: A total of 62.456 clinic samples were accepted in the microbiology laboratory between 2019 and 2024. The mycobacterial culture was performed by searching for acid-resistant bacilli microscopically and parallel inoculation media [solid Löwenstein-Jensen (L-J) and MGIT 960 liquid]. Those growing in the MGIT 960 system were identified using BD MGIT TBC Identification test kits that detect the MPT64 antigen. AFS and MPT64 antigenpositive samples were identified as Mycobacterium tuberculosis complex (MTBC) while AFS-positive samples and MPT64 antigen-negative results were classified as non-tuberculous mycobacteria (NTM). Drug susceptibility testing was performed with the BACTEC MGIT 960 SIRE kit. Susceptibility to NTM samples was not performed. Result: Out of a total of 120.829 samples, 95.101 were lung samples and 25.728 were extrapulmonary samples. AFS positivity was detected in 2961 (2.4%) samples. MTBC grew in 6854 (5.6%) samples, and NTM grew in 1506 (1.24%) samples. Contamination was detected in 7171 (5.9%) media. Two thousand one hundred and sixty-nine susceptibility tests were performed. Considering antibiotic resistance rates, isoniazid resistance was detected in 154 (7%), rifampicin resistance in 140 (6.4%), ethambutol resistance in 18 (0.8%), and streptomycin resistance in 120 (0.5%) samples. All four-drug resistance was observed in 91 (4.1%) samples. AFP positivity and resistance rates for rifampicin have decreased significantly, while there have been no significant changes in NTM rates over the years. Conclusions: When our data was determined, the sensitivity of microscopy was low. It is understood that mycobacterial culture and microscopy must be evaluated together to exclude tuberculosis infection. The high mycobacterial culture positivity rate, which is 5.6%, is due to the high number of follow-up patients and new referrals. It is seen that the change in sensitivity rates is due to the period of the COVID-19 epidemic, and it is similar to World Health Organization (WHO) data.

[Study on the direct economic burden and relevant influencing factors of 233 multidrug/rifampicin-resistant pulmonary tuberculosis patients in Jiangsu Province].

Objective: To explore the direct economic burden and factors affecting out-of-pocket direct costs of multidrug-/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) patients in Jiangsu Province. Methods: MDR/RR-PTB patients diagnosed and treated at 13 municipal tuberculosis (TB)-designated hospitals in Jiangsu Province between January 1, 2021, and December 31, 2022, were included, and basic information and direct economic costs were obtained through questionnaires and hospital information systems. Stepwise multiple linear regression was used to analyze the factors influencing patients' out-of-pocket direct costs. Results: The age of the 233 MDR/RR-PTB patients was (44.04±15.64) years. The M(Q1, Q3) direct medical expense of the patients was 134 051.00 (98 934.01,163 205.73) Yuan, of which the M(Q1,Q3) reimbursement by health insurance or policy reduction was 100 462.10 (78 120.00,130 816.00) Yuan, and the M(Q1,Q3) out-of-pocket direct medical expense was 21 694.62 (14 734.83,37 813.00) Yuan. The M(Q1,Q3) direct non-medical expense was 4 971.00 (3 138.00,7 870.00) Yuan. Age, registered residence location, TB resulting in divorce or separation from spouse or partner, drug resistance test results, and treatment regimens were the influencing factors associated with out-of-pocket direct costs for MDR/RR-PTB patients. Conclusions: The direct economic burden caused by MDR/RR-PTB in Jiangsu Province is heavy. It is necessary to emphasize psychological guidance and care for MDR/RR-PTB patients, improve the diagnosis, treatment, and management of MDR/RR-PTB, and effectively reduce the economic burden of MDR/RR-PTB patients.