UNASSIGNED: Antituberculosis drugs may cause mild, moderate or severe adverse drug reactions (ADR) leading to poor compliance. Description of the pattern of ADR and their related factors can help tuberculosis (TB) control program as part of the WHO programs. This study aims to investigate the incidence of ADR and associated factors among TB patients in northern Iran.
UNASSIGNED: This is a retrospective cohort study. The required information, including year of diagnosis, age, gender, residence area, nationality, HIV co-morbidity, history of anti TB treatment and ADR, was obtained from the Deputy of Health, Mazandaran University of Medical Sciences, Iran. All data were analyzed using SPSS version 21 software.
UNASSIGNED: Out of 3903 TB patients, 136 (3.5%) experienced major ADR. The incidence of ADR for men and women as well as for those with and without previous treatment history were 3.9% vs. 3.3% and 5.3% vs. 3.4%, respectively (p>0.05). Multiple logistic regression models showed a higher chance of ADR among those aged over 59 compared with those aged under 29 (OR=2.63, 95% confidence interval: 1.54-4.49).
UNASSIGNED: Age over 59 can be considered a risk factor for ADR with anti-TB drug administration.
UNASSIGNED: Antituberkulostatika (AT) können leichte, mittelschwere oder schwere unerwünschte Arzneimittelwirkungen (UAW) verursachen, die zu einer schlechten Compliance führen. Die Beschreibung des Musters von UAW und der damit zusammenhängenden Faktoren kann dem Tuberkulose(TB)-Kontrollprogramm helfen. Ziel der Studie ist es, die Häufigkeit von UAW und die damit zusammenhängenden Faktoren bei TB-Patienten im Norden des Irans zu untersuchen.
UNASSIGNED: Es handelt es sich um eine retrospektive Kohortenstudie. Die erforderlichen Informationen einschließlich Diagnosejahr, Alter, Geschlecht, Wohnort, Staatsangehörigkeit, HIV-Komorbidität, Vorgeschichte der TB-Behandlung und UAW, wurden vom stellvertretenden Gesundheitsamt der Mazandaran Universität für Medical Sciences, Iran, bereitgestellt und mit der Software SPSS Version 21 ausgewertet.
UNASSIGNED: Von 3903 TB-Patienten traten bei 136 (3,5%) schwerwiegende UAW auf. Die Häufigkeit von UAW bei Männern bzw. Frauen betrug bei vorheriger Behandlung 3,9% bzw. 3,3%, ohne vorherige Behandlung 5,3% bzw. 3,4% (p>0,05). Multiple logistische Regressionsmodelle ergaben, dass die Wahrscheinlichkeit einer UAW bei über 59-Jährigen höher war als bei unter 29-Jährigen (OR=2,63, 95 % Konfidenzintervall: 1,54–4,49).
UNASSIGNED: Ein Alter über 59 Jahren kann als Risikofaktor für UAW gegen Antituberkulostatika angesehen werden.

Topological indices are molecular descriptors used in QSPR modelling to predict the physicochemical properties of molecules. Topological indices are used in numerous applications in drug design. In this work, we compute the neighbourhood degree-based topological indices of 15 antituberculosis drugs, we studied the QSPR analysis of these drugs using support vector regression. The efficiency of support vector regression is determined by comparing it with the classical linear regression. Our QSPR model further shows the superiority of the SVR model as a better predictive model in QSPR analysis of the physical properties of antituberculosis drugs. The findings in this study are a further contribution to the field of chemical graph theory and drug design, providing a deeper understanding of neighbourhood degree-based topological indices and their predictive capabilities in QSPR model.

DRESS related to first-line antituberculosis drugs (ATD) is a challenging diagnosis. With a long-lasting combined treatment of 4-concomitantly administrated drugs, identification of the culprit drug remains difficult and may expose patients to treatment interruption and affect their outcome. A 42-year-old female, treated with isoniazid, rifampicin, pyrazinamide and ethambutol for multifocal tuberculosis, developed, 40 days later, hyperthermia, facial edema, cervical lymphadenopathy and generalized exanthema. Biological test results revealed eosinophilia, atypical lymphocytes, and liver injury. DRESS was suspected, and ATD were withdrawn. As patch tests for the 4 ATD showed negative results, we decided to reintroduce pyrazinamide, ethambutol and rifampicin separately with a 3-day interval. Pyrazinamide and rifampicin were tolerated. However, after receiving ethambutol, she developed fever and generalized rash, with no biological abnormalities. Since ethambutol was claimed to be the culprit drug, isoniazid was added, and 10 hours later, the patient developed fever, facial edema, generalized rash, eosinophilia and liver injury. This clinical and biological pattern resolved 2 weeks later. This report suggests a hypersensitivity relapse to ethambutol after isoniazid-induced DRESS.

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

UNASSIGNED: Tuberculosis of the central nervous system is unusual and accounts for 1 % of all cases of tuberculosis in the world. The pituitary location is even scarcer.
METHODS: A 14-year-old girl presented with polyuria-polydipsia syndrome and menstrual irregularity. MRI showed an intrasellar lesion of the pituitary gland. She underwent transsphenoidal surgery for histopathological diagnosis and removal of the lesion. Histological findings were consistent with a tuberculoma. She was put on anti-tuberculosis drugs and is being followed up.
UNASSIGNED: In endemic areas, pituitary tuberculosis should be considered in the differential diagnosis of pituitary tumors. The histological examination will guide the diagnosis. Sometimes, other complementary examinations such as the tuberculin skin test can be of great help when the histology is not conclusive. Medical treatment can be curative, however, surgery can be necessary for decompression.
CONCLUSIONS: In addition to being the first case of histologically proven primary pituitary tuberculosis in a child reported in Morocco, the present case is unique in the way that the extensive radiological examinations did not reveal any evidence of other systemic or pulmonary tuberculosis.

OBJECTIVE: The incidence of tuberculosis (TB) in intensive care units (ICUs) can be as high as 3% in high-burden settings, translating to more than 7,500 patients admitted to the ICU annually. In resource-limited settings, the lack or absence of intravenous formulations of drug-sensitive antituberculosis medications necessitates healthcare practitioners to crush, dissolve, and administer the drugs to critically ill patients via a nasogastric tube (NGT). This off-label practice has been linked to plasma concentrations below the recommended target concentrations, particularly of rifampicin and isoniazid, leading to clinical failure and the development of drug resistance. Optimizing the delivery of crushed drug-sensitive antituberculosis medication via the NGT to critically ill patients is of utmost importance.

Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis (TB) and the most severe form of extrapulmonary TB. It often presents with non-specific symptoms initially and has a high mortality and disability rate. With good central nervous system penetration, linezolid is recommended for treating drug-resistant, severe, or refractory tuberculous meningitis in China. Despite the benefits of linezolid on TBM treatment, the adverse effects of long-term therapy, such as myelosuppression, peripheral neuritis, and optic neuritis, are notable and can be severe and even life-threatening, leading to discontinuation and compromising treatment expectations. Contezolid is a novel oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021, which has a more favorable safety profile than linezolid in terms of myelosuppression and monoamine oxidase inhibition. Here we first report a case of TBM in a patient who was intolerant to antituberculosis treatment with linezolid and achieved good efficacy and safety results after the compassionate use of contezolid. Given the widespread use of linezolid in TB treatment and the potential risks for long-term use, multi-center prospective controlled clinical trials in TB and TBM patients are needed to investigate the appropriate use of contezolid further.

Data on protein binding are incomplete for first-line antituberculosis drugs, and lacking for second-line antituberculosis drugs that are used extensively for multi-drug-resistant tuberculosis (levofloxacin, linezolid and moxifloxacin). Thus, the main purposes of this study were to investigate: (i) the relationship between carrier protein concentration and drug binding; and (ii) the feasibility of predicting free drug concentration using in-vitro and in-vivo results. In-vitro experiments were performed on spiked plasma mimicking real-case samples (drug combinations from clinical practice). Median in-vivo protein binding was 1.5% for ethambutol, 9.7% for isoniazid, 0.7% for pyrazinamide and 88.2% for rifampicin; and median in-vitro protein binding was 26.2% for levofloxacin, 12.8% for linezolid and 46.3% for moxifloxacin. Albumin concentration (<30 g/L) had a moderate impact on moxifloxacin binding and a strong impact on levofloxacin, linezolid and rifampicin binding. Determination of the free drug concentration seems to be of little value for ethambutol, isoniazid, moxifloxacin and pyrazinamide; limited value for linezolid because of its low binding; and major value for rifampicin in hypoalbuminaemic patients with tuberculosis, and levofloxacin because total concentration was an inaccurate reflection of free concentration. The free concentration predicted by the mathematical model was suitable for levofloxacin and linezolid, whereas the real free concentration should be measured for rifampicin. Further investigations should be carried out to investigate the benefit of using free concentration for levofloxacin, linezolid and rifampicin, particularly in the critical period of active tuberculosis associated with hypoalbuminaemia.

BACKGROUND: India has the highest cases of tuberculosis worldwide. According to WHO (2022), the incidence of tuberculosis in India is 210 per 100,000 population. Their incidence of new positive smear cases is 75 per 100,000 population per year. In tuberculosis, the level of albumin decreases while globulin increases leading to a low albumin to globulin (A/G) ratio, and electrophoresis of serum proteins are good diagnostic approach and provides essential information for monitoring treatment outcomes.
METHODS: The present study includes 50 cases of pulmonary tuberculosis and 50 age-sex-matched healthy controls. Initially, serum protein estimation and electrophoresis were performed in newly diagnosed patients and controls. All drugs were given as National Tuberculosis Elimination Programme (NTEP) guidelines and blood samples were collected at two-month, four-month, and six-month intervals, and different serum protein fractions were compared and analyzed.
RESULTS: The total serum protein was significantly lower in the cases than in the controls; 6.12±0.61 vs. 7.02±0.56 g/dL (p˂0.0020, t-value=3.12). The mean serum albumin was also significantly lower in the cases compared to the controls; 1.65±0.69 vs. 3.87±0.47g/dL (p˂0.0001, t-value=10.98). The α1 globulin started to rise after four months of treatment and at six months level was 0.262±0.32 g/dL. The level of γ globulin continuously decreases after antituberculous treatment to 1.56±0.67 gm/dL at six months.
CONCLUSIONS: The cause of the decrease in total protein and albumin may be due to malnutrition leading to low cellular immunity. Serum protein level and protein electrophoresis should be analyzed as routine tests in patients before, during, and after treatment. It helps us in identifying patients at risk of pulmonary tuberculosis as well prognosis of the disease. This study is a valuable guide in deciding the effective management of tuberculosis patients with drug treatment plans and appropriate dietary intake. Hence, it highlights the complex relationship that exists between poverty and disease.

OBJECTIVE: To describe the phenotype of DRESS syndrome induced by antituberculosis drugs.
METHODS: Descriptive study, withdrawn from the review of the records of patients with DRESS syndrome, identified in the interconsultation of the Department of Research in Immunogenetics and Allergy, of the Insti-tuto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, among 2014 and 2020. Frequency analysis was performed. The associations between biomarkers and latency are calculated with the χ2 test and log-rank, and the evaluation of the change in the biomarkers with the Wilcoxon test. The value of p < 0.05 is considered statistically significant. For data analysis, the SPSS v.21 program was obtained.
RESULTS: 15 patients were identified; represented by 0.02% of total cases treated in the Department for so-meimmuno-allergic condition (15/7052); the main symptomatology were: rash (100%), eosinophilia (93%), fe-ver (80%), adenomegaly (60%), kidney damage (40%), liver damage (33%), and latency of 21 days. Liver damage was associated with prolonged latency (p = 0.02). After treatment, the total levels of eosinophils (p < 0.001) and liver and kidney biomarkers (p < 0.04) decreased. DRESS syndrome induced by antituberculosis drugs is not associated with the number of drugs prescribed or with the pattern of resistance of Mycobacterium tuberculosis.
CONCLUSIONS: DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids.
OBJECTIVE: Describir el fenotipo del síndrome de DRESS inducido por fármacos antituberculosos.
UNASSIGNED: Estudio descriptivo efectuado a partir de la revisión de los expedientes de pacientes con síndrome de DRESS, identificados en la interconsulta del Departamento de Investigación en Inmunogénetica y Alergia, del Instituto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, entre 2014 y 2020. Se realizó análisis de frecuencias. Las asociaciones entre biomarcadores y latencia se calcularon con la prueba de χ2 y log-rank, y la evaluación del cambio en los biomarcadores con la prueba de Wilcoxon. Se consideró esta-dísticamente significativo el valor de p < 0.05. Para el análisis de los datos se utilizó el programa SPSS v.21.
RESULTS: Se identificaron 15 pacientes, que representaron el 0.2% de los casos atendidos en el Departa-mento por algún padecimiento inmuno-alérgico (15/7052); las principales manifestaciones fueron: exantema (100%), eosinofilia (93%), fiebre (80%), adenomegalia (60%), daño renal (40%), daño hepático (33%) y latencia de 21 días. El daño hepático se asoció con latencia prolongada (p = 0.02). Posterior al tratamiento disminu-yeron las concentraciones totales de eosinófilos (p < 0.001) y biomarcadores hepáticos y renales (p < 0.04). El síndrome de DRESS inducido por fármacos antituberculosos no se asoció con la cantidad de fármacos prescritos ni con el patrón de resistencia de Mycobacterium tuberculosis.
CONCLUSIONS: El síndrome de DRESS inducido por fármacos antituberculosos es una reacción clínica atípica, similar a otros tipos de síndrome de DRESS que responden favorablemente a corticosteroides sisté-micos.