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Introduction: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare. Case presentation: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction. Conclusions: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects. [ABSTRACT FROM AUTHOR]

Abstract Introduction Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare. Case presentation We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient’s symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction. Conclusions This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects.

Background: Tuberculosis (TB) gumma (metastatic tuberculous abscess) is a rare form of cutaneous TB, generally occurring in malnourished and immunocompromised patient. Case: A 24 year old man with a chief complaint of ulcers accompanied by a thick pigmented crusts on the neck and left abdomen without pain since 3 months ago. Initially, 6 months ago a small skin coloured lump the size of a green bean seed arised on the stomach and neck, not itchy or painful. One month later, the mass got bigger, ulcerated, and pus drainage were seen. The patient was also currently diagnosed with pulmonary TB. Dermatological examination showed an ulcer with a diameter of 10 cm with crusts and pus with irregular edges and hyperpigmentation in the left colli region and an ulcer with a diameter of 15 cm with crusts and pus with irregular edges and hyperpigmentation in the left lumbar region. The results of histopathological examination of the dermis showed fibrocollagenous connective tissue with infiltration of inflammatory lymphocytes and PMN cells, localized clusters of epithelioid cells with central necrosis and Langhans multinucleated giant cells were found. Discussion: Gumma tuberculosis is a multibacillary variant of cutaneous TB with a focus on hematogenous spread. Antituberculosis drugs are given according to the phase and the dose is according to the patient's body weight. Conclusion: A case of gumma tuberculosis has been reported in an immunocompetent young adult patient with pulmonary tuberculosis. The prognosis in patients is generally good. Pendahuluan: Tuberkulosis (TB) gumma (abses tuberkulosis metastatik) adalah bentuk TB kutis yang jarang, umumnya terjadi pada keadaan malnutrisi dan imunokompromais. Kasus: Seorang laki-laki berusia 24 tahun dengan keluhan utama luka borok disertai dengan keropeng hitam yang tebal pada leher dan perut kiri yang tanpa rasa nyeri sejak 3 bulan lalu. Awalnya, 6 bulan yang lalu pasien merasakan adanya benjolan kecil seukuran biji kacang hijau pada perut dan leher yang sewarna kulit dan tidak terasa gatal maupun nyeri. Satu bulan setelahnya benjolan dirasakan semakin membesar kemudian pecah dan mengeluarkan nanah. Pasien saat ini juga didiagnosis dengan TB paru. Dari pemeriksaan dermatologis tampak ulkus dengan diameter 10 cm disertai krusta dan pus dengan tepi ireguler dan hiperpigmentasi pada regio colli sinistra dan ulkus dengan diameter 15 cm disertai krusta dan pus dengan tepi ireguler dan hiperpigmentasi pada regio lumbalis sinistra. Hasil histopatologis dari jaringan regio abdomen dekstra menunjukan bagian dermis terdiri dari jaringan ikat fibrokolageneus dengan infiltrasi sel-sel radang limfosit dan PMN, setempat tampak kelompokan sel-sel epiteloid dengan nekrosis sentral dan dijumpai Langhans multinucleated giant cell. Diskusi: Tuberkulosis gumma merupakan varian multibasiler dari TB kutis dengan fokus penyebaran secara hematogen. Obat antituberkulosis (OAT) diberiksan sesuai fase dan dosis disesuaikan dengan berat badan pasien. Kesimpulan: Telah dilaporkan satu kasus tuberkulosis gumma pada pasien dewasa muda imunokompeten yang mengalami tuberkulosis paru. Prognosis pada pasien umumnya baik.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusions: Age over 59 can be considered a risk factor for ADR with anti-TB drug administration.

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.

ABSTRACT In low-resource settings, access to intravenous formulations of antituberculosis drugs is lacking or absent. Thus, critically ill patients with tuberculosis (TB) are often treated with readily available tablets which are crushed, mixed with water, and administered via a nasogastric tube (NGT). This has been associated with plasma concentrations below the recommended target, particularly of rifampicin (RIF) and isoniazid (INH), leading to clinical failure and development of drug resistance. We aimed to identify physiochemical factors contributing to lower plasma concentrations of antituberculosis drugs when administered in this manner using laboratory-based techniques, including the addition of ascorbic acid (AA) for optimum administration. Aqueous solubility of crushed medication using the inversion mixing method was evaluated against easily implementable mixing methods (sonication/vortexing) with or without AA. Stability of crushed medication in simulated-gastrointestinal fluids was evaluated with or without AA. Drug loss via NGT surface adsorption was quantitatively determined. RIF demonstrated poor aqueous solubility of 5.2%. Incorporation of AA improved the solubility to 29.7%, and with the addition of mixing techniques, solubility improved to 86.3%. Mixing methods with AA further improved the solubilities of both INH (80%) and pyrazinamide (PZA, 64%) to over 90%. AA also showed protective effects against unstable RIF in simulated-gastric fluid. Conventional flushing of NGT after drug administration with 10 mL of water resulted in drug losses of 1.5%, 0.13%, and 1.4% for RIF, INH, and PZA, respectively. An additional flushing step halved this amount. These interventions may improve the poor plasma concentrations of crushed antituberculosis drugs in critically ill patients. IMPORTANCE 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.

This study was designed to explore whether Chinese herbals could enhance the clinical efficacy of levofloxacin and a combination of antituberculosis drugs. To this end, a group of pulmonary patients were treated with pyrazinamide, isoniazid, ethambutol, and levofloxacin (control), and the other group (treatment) also received a combination of extra Chinese herbal compounds. After 6 months of therapy, the total efficiency of lesion absorption in the treatment group was higher than in the control group. The treatment group had a higher peak expiratory flow rate, a higher percentage of forced vital capacity, a higher percentage of the first second of forced expiration, higher levels of immunoglobulin A, immunoglobulin G, immunoglobulin M, and CD4+, and lower levels of CD8+ compared to the control group. The levels of proinflammatory cytokines were lower, the sputum conversion rate was higher, and the recurrence rate was lower in the treatment group than the control group. After therapy, the treatment group had higher scores in the quality of daily life, spirit, appetite, fatigue, and sleep assessments. In conclusion, therapy with levofloxacin and antituberculosis drugs combined with Chinese herbal compounds for patients with pulmonary tuberculosis could effectively relieve the inflammatory reaction, promote lesion absorption, and thus improve their lung function and promote recovery. [ABSTRACT FROM AUTHOR]

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.

The aim of this study was to create nanoparticles of human serum albumin immobilized with anti-TB drugs (rifampicin, isoniazid) using the desolvation method. Central Composite Design (CCD) was applied to study the effect of albumin, urea, L-cysteine, rifampicin and isoniazid concentration on particle size, polydispersity and loading degree of the drugs. The optimized nanoparticles were spherical in shape with an average particle size of 216.7 ± 3.7 nm and polydispersity of 0.286 ± 4.9. The loading degree of rifampicin and isoniazid in the optimized nanoparticles were 44% and 27%, respectively. The obtained nanoparticles were examined by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC); the results showed the absence of drug–polymer interactions. The drug release from the polymer matrix was studied using dialysis membranes. [ABSTRACT FROM AUTHOR]

Aim: Serum microRNA‐122 (miR‐122) is a novel biomarker for drug‐induced liver injury, with good sensitivity in the early diagnosis of paracetamol‐induced liver injury. We describe miR‐122 concentrations in participants with antituberculosis drug‐induced liver injury (AT‐DILI). We explored the relationship between miR‐122 and alanine aminotransferase (ALT) concentrations and the effect of N‐acetylcysteine (NAC) on miR‐122 concentrations. Methods: We included participants from a randomized placebo‐controlled trial of intravenous NAC in AT‐DILI. ALT and miR‐122 concentrations were quantified before and after infusion of NAC/placebo. We assessed correlations between ALT and miR‐122 concentrations and described changes in ALT and miR‐122 concentrations between sampling occasions. Results: We included 45 participants; mean age (± standard deviation) 38 (±10) years, 58% female and 91% HIV positive. The median (interquartile range) time between pre‐ and post‐infusion biomarker specimens was 68 h (47‐77 h). The median pre‐infusion ALT and miR‐122 concentrations were 420 U/L (238‐580) and 0.58 pM (0.18‐1.47), respectively. Pre‐infusion ALT and miR‐122 concentrations were correlated (Spearman's ρ =.54, P =.0001). Median fold‐changes in ALT and miR‐122 concentrations between sampling were 0.56 (0.43‐0.69) and 0.75 (0.23‐1.53), respectively, and were similar in the NAC and placebo groups (P =.40 and P =.68 respectively). Conclusions: miR‐122 concentrations in our participants with AT‐DILI were considerably higher than previously reported in healthy volunteers and in patients on antituberculosis therapy without liver injury. We did not detect an effect of NAC on miR‐122 concentrations. Further research is needed to determine the utility of miR‐122 in the diagnosis and management of AT‐DILI. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the steady-state pharmacokinetic profiles of 3-month weekly rifapentine plus isoniazid (3HP) in children with latent tuberculosisinfection (LTBI). We also assessed other factors, including tablet integrity, food, and pharmacogenetics. Methods: During the 3HP treatment, blood and urine samples were collected in week 4. Isoniazid and rifapentine levels were measured using a high-performance liquid chromatography technique. The genetic variation of arylamine N-acetyltransferase 2 (NAT2) and arylacetamide deacetylase (AADAC) were assessed by the MassARRAY®. Safety and clinical outcomes at week 48 were monitored. Results: A total of 12 children with LTBI (age 3.8 [range 2.1-4.9 years old]) completed the treatment (isoniazid and rifapentine dose 25.0 [range 21.7-26.8] and 25.7 [range 20.7-32.1] mg/kg, respectively). No serious adverse events or active TB occurred. Tablet integrity was associated with decreased area under the concentration-time curve (91 vs 73 mg.h/l, P= 0.026) and increased apparent oral clearance of isoniazid (0.27 vs 0.32 l/h/kg, P= 0.019) and decreased rifapentine's renal clearance (CLR, 0.005 vs 0.003 l/h, P= 0.014). Food was associated with increased CLR of isoniazid (3.45 vs 8.95 l/h, P= 0.006) but not rifapentine. Variability in NAT2 and AADAC did not affect the pharmacokinetics of both drugs. Conclusion: There is high variability in the pharmacokinetic profiles of isoniazid and rifapentine in young children with LTBI. The variability was partly influenced by tablet integrity and food, but not pharmacogenetics. Further study in a larger cohort is warranted to display the relationship of these factors to treatment outcomes.

The burden of tuberculosis (TB) disease is a global health challenge accounting for thousands of deaths. TB is unevenly distributed in South Africa, with some provinces having more than 70% of the TB burden. In Mpumalanga Province, TB is ranked as the sixth leading cause of death. Antituberculosis agents are usually costly, with numerous unwanted side effects. This has prompted the major use of herbs which have an imperative biological role against tuberculosis and are easily accessible. A comprehensive review of plants used as a combating strategy against tuberculosis in Mpumalanga Province was conducted. An in-depth literature search was performed using scientific databases, theses, dissertations and ethnobotanical books. Twenty-four (24) plant species were reported by the people of Mpumalanga for the treatment of tuberculosis. Fifteen (15) plant species have been investigated for antituberculosis activities, and seven antimycobacterial compounds were successfully isolated. This review validates the use of plants against tuberculosis in Mpumalanga Province and, thus, identified species that may be explored for further scientific studies. [ABSTRACT FROM AUTHOR]

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 Instituto 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%), fever (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. Conclusion: DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an ancient human disease caused by Mycobacterium tuberculosis which affects the lungs, making pulmonary disease the most common presentation. Herbal medicine began to be developed as hepatoprotection. The hepatoprotection effects of Plantago major extract on serum glutamic pyruvic transaminase (SGPT), liver tissue Malondialdehyde (MDA), and histopathological changes were evaluated in rifampicin and isoniazid-induced hepatitis rats. Thirty male Wistar rats were divided into 6 groups: Group I received 1 % PGA, with hepatitis induced in the remaining groups by rifampicin and isoniazid 50 mg/kg BW/day, group II was only given rifampicin and isoniazid, group III was given curcuma 10.8 mg/kg BW/day and groups IV (PM1), V (PM2), and VI (PM3) were given Plantago major extract at a dose of 20.3, 40.5, and 81 mg/kg BW/day, respectively. The rats were treated for 28 days. Administration of Plantago major extract (20.3 and 40.5 mg/kg BW/day) inhibited the elevation of serum SGPT and MDA levels, with less portal inflammation than the negative control group. The rats treated with the higher dose of 81 mg/kg BW/day had serum SGPT, MDA, and percentage portal inflammation equivalent to the negative control group. The Plantago major extract at a dose of 20.3 and 40.5 mg/kg BW can inhibit the elevated serum SGPT. Plantago major extract exerts dose-dependent hepatoprotection effects in a rifampicin-isoniazid induced hepatitis rat model by reducing elevated levels of SGPT, liver tissue MDA, as well as the percentage of portal inflammation. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is among the deadliest infectious diseases worldwide. Although the existing antituberculosis (anti-TB) drugs remain to be effective, the administration of these complex anti-TB drug combinations with obvious toxicity often leads to patients’ nonadherence. This may contribute toward the emergence of drug-resistant strains as well as lead to treatment failure and relapse. Therefore, in the past half century, the main focus of anti-TB drug research was to reduce the frequency of administration and toxicity and improve patients’ compliance and drug sensitivity. Following these principles, the development of engineered biosafety materials is one of the most effective and promising methods in resolving these challenges. Compared with traditional drugs, biosafety materials provide a viable platform for treating TB, which are beneficial in reducing the frequency of drug administration and systemic toxicity, improving patients’ compliance and drug sensitivity, and enhancing drug targeting. In this review, we summarized the application of biosafety materials in treatment of TB in recent years and discussed the challenges faced when developing a safe, more effective, and economical pharmacotherapy against TB.

Background: The antituberculosis drugs (ATDs), isoniazid, rifampicin, pyrazinamide and ethambutol prompt extreme hepatic and renal damage during treatment of tuberculosis. The present study aimed to investigate protective potential of naringenin against ATDs induced hepato-renal injury. Methods: Rats were administered with ATDs (pyrazinamide; 210, ethambutol; 170, isoniazid; 85, rifampicin; 65 mg/kg b.wt) orally for 8 weeks (3 days/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg b.wt) conjointly for 8 weeks (3 days/week alternately to ATDs administration) and silymarin (50 mg/kg b.wt) as positive control. Results: Exposure to ATDs caused significant increase in interleukin-6 (IL-6), triglycerides, cholesterol, bilirubin whereas depletion in insulin like growth factor-1 (IGF-1), albumin and glucose in serum. Endogenous antioxidant enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate-dehydrogenase (G-6-PDH) were diminished in liver and kidney tissues with parallel increase in triglycerides, cholesterol, microsomal LPO and aniline hydroxylase (CYP2E1 enzyme). Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles after 8 weeks of exposure to ATDs. Conclusions: Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, CYP2E1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin has excellent potential to protect ATDs induced hepato-renal injury by altering oxidative stress, modulation of antioxidant enzymes, serum cytokines and ultra-structural changes. [ABSTRACT FROM AUTHOR]

Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes. [ABSTRACT FROM AUTHOR]

(Z)-1,2-Bis[4-oxo-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-8-yl]diazene oxide, C28H24F6N6O3S2, was obtained and its structure determined while attempting to crystallize and structurally characterize 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one, a simplified analogue of the antituberculosis clinical drug candidate BTZ043. X-ray crystallography revealed the structure of the azoxy compound to be comprised of two benzothiazinone moieties linked by a Z-configured azoxy group in an almost coplanar arrangement. In the crystal, the molecules are densely packed, revealing a herringbone pattern. [ABSTRACT FROM AUTHOR]

Tuberculosis kutis adalah bentuk langka dari mikrobiosis yang menyumbang 1% hingga 2% dari semua bentuk tuberculosis ekstrapulmonal. Dilaporkan seorang pasien pria,18 tahun, datang dengan keluhan luka lecet pada pergelangan kaki yang sudah dialami selama 6 tahun. Pemeriksaan histopatologi membuktikan bahwa pasien mengalami tuberculosis kutis. Pengobatan tuberculosis kutis sama dengan pengobatan tuberculosis pulmonal. Pasien diberikan regimen obat antituberkulosis (OAT) selama 6 bulan. [ABSTRACT FROM AUTHOR]

• We studied the pharmacokinetic profiles of 3-month weekly rifapentine plus isoniazid in young children with latent tuberculosis infection. • The area under the curve (AUC) 0-24h of isoniazid was lower in those receiving crushed tablets. • Crushed tablets showed a trend AUC reduction in rifapentine than whole tablets. • Food affected the renal clearance of isoniazid but not rifapentine. This study investigated the steady-state pharmacokinetic profiles of 3-month weekly rifapentine plus isoniazid (3HP) in children with latent tuberculosisinfection (LTBI). We also assessed other factors, including tablet integrity, food, and pharmacogenetics. During the 3HP treatment, blood and urine samples were collected in week 4. Isoniazid and rifapentine levels were measured using a high-performance liquid chromatography technique. The genetic variation of arylamine N-acetyltransferase 2 (NAT2) and arylacetamide deacetylase (AADAC) were assessed by the MassARRAY®. Safety and clinical outcomes at week 48 were monitored. A total of 12 children with LTBI (age 3.8 [range 2.1-4.9 years old]) completed the treatment (isoniazid and rifapentine dose 25.0 [range 21.7-26.8] and 25.7 [range 20.7-32.1] mg/kg, respectively). No serious adverse events or active TB occurred. Tablet integrity was associated with decreased area under the concentration-time curve (91 vs 73 mg.h/l, P = 0.026) and increased apparent oral clearance of isoniazid (0.27 vs 0.32 l/h/kg, P = 0.019) and decreased rifapentine's renal clearance (CL R , 0.005 vs 0.003 l/h, P = 0.014). Food was associated with increased CL R of isoniazid (3.45 vs 8.95 l/h, P = 0.006) but not rifapentine. Variability in NAT2 and AADAC did not affect the pharmacokinetics of both drugs. There is high variability in the pharmacokinetic profiles of isoniazid and rifapentine in young children with LTBI. The variability was partly influenced by tablet integrity and food, but not pharmacogenetics. Further study in a larger cohort is warranted to display the relationship of these factors to treatment outcomes. [ABSTRACT FROM AUTHOR]

Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

The aim of this study was to create nanoparticles of human serum albumin immobilized with anti-TB drugs (rifampicin, isoniazid) using the desolvation method. Central Composite Design (CCD) was applied to study the effect of albumin, urea, L-cysteine, rifampicin and isoniazid concentration on particle size, polydispersity and loading degree of the drugs. The optimized nanoparticles were spherical in shape with an average particle size of 216.7 ± 3.7 nm and polydispersity of 0.286 ± 4.9. The loading degree of rifampicin and isoniazid in the optimized nanoparticles were 44% and 27%, respectively. The obtained nanoparticles were examined by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC); the results showed the absence of drug–polymer interactions. The drug release from the polymer matrix was studied using dialysis membranes.

Laccase from Trametes villosa was immobilized by CLEAs (cross-linked enzyme aggregates), biochemically characterized and applied for the degradation of the antibiotics rifampicin (RIF) and isoniazid (INH). The extracellular laccase purified by Sephadex G-100 chromatography presented a specific activity of 530.07 U/mg with a purification factor of 6.3-fold. SDS–PAGE followed by zymogram provided a single band, indicating that laccase from T. villosa was a monomeric protein with molecular mass of about 45 kDa. The optimum pH and temperature values for the laccase CLEAs (Lac-CLEAs) were 4.0 and 60 °C, respectively, and they remained more active over a broader range of pH and temperature during 60 min of incubation as compared to the partially purified free form. Lac-CLEAs presented less affinity for ABTS than their corresponding free enzyme, and the values for Km and Vmax were 3.521 mM and 137.0 mM min, respectively. Free laccases and Lac-CLEAs were used for simultaneous biodegradation of 5 mg/L RIF and INH in aqueous solutions. Results obtained by high-performance liquid chromatography (HPLC) revealed that 95% and 94% of RIF were biodegraded by free and immobilized laccase, respectively. Lac-CLEAs degraded more than twofold (71%) the amount of INH degraded by the free enzyme (32%). A microbial susceptibility assay demonstrated a stronger inhibition of Staphylococcus aureus by laccase-treated samples, with lower MIC values in comparison to control samples. Article Highlights: Trametes villosa produced 12 U/mL of laccase in semi solid cultures. Apparent molecular mass of the laccase from T. villosa was 45 kDa. Lac-CLEAs were more stable than the free enzyme at pH 6.0 and T ≥ 60 °C. Both free laccase and Lac-CLEAs biodegraded rifampicin and isoniazid. Isoniazid was more efficiently degraded by Lac-CLEAs. [ABSTRACT FROM AUTHOR]

Diagnosis of tuberculous spondylodiscitis is difficult because clinical findings usually are nonspecific and radiological features may mimic other bacterial, fungal, inflammatory and neoplastic diseases. We present the first reported case of tuberculous spondylodiscitis in a 56-year-old man successfully treated by rifampicin-containing anti tuberculosis regimen with close follow-up of serum cyclosporine levels.

The burden of tuberculosis (TB) disease is a global health challenge accounting for thousands of deaths. TB is unevenly distributed in South Africa, with some provinces having more than 70% of the TB burden. In Mpumalanga Province, TB is ranked as the sixth leading cause of death. Antituberculosis agents are usually costly, with numerous unwanted side effects. This has prompted the major use of herbs which have an imperative biological role against tuberculosis and are easily accessible. A comprehensive review of plants used as a combating strategy against tuberculosis in Mpumalanga Province was conducted. An in-depth literature search was performed using scientific databases, theses, dissertations and ethnobotanical books. Twenty-four (24) plant species were reported by the people of Mpumalanga for the treatment of tuberculosis. Fifteen (15) plant species have been investigated for antituberculosis activities, and seven antimycobacterial compounds were successfully isolated. This review validates the use of plants against tuberculosis in Mpumalanga Province and, thus, identified species that may be explored for further scientific studies.

Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation. [ABSTRACT FROM AUTHOR]

Based on plasma endotoxin/toll-like receptor-4/nuclear factor-kappa B signal pathway to investigate the protective effect of soothing liver mixture on mice with liver injury induced by antituberculosis drugs. A total of 72 Sprague Dawley male rats were randomly divided into blank control group, model group, silymarin group and soothing liver mixture group (low, medium and high dosage), with 12 rats in each group. 16 h after the last administration, the pathological changes of liver tissue were observed by hematoxylin eosin staining; blood samples were taken from eyeball to detect liver function indexes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) oxidative stress indexes (superoxide dismutase, malondialdehyde, glutathione peroxidase) and inflammatory factors (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha) and the content of plasma endotoxin in plasma; the microRNA expression levels of toll-like receptor-4 and nuclear factor-kappa B in rat liver were detected by real time reverse transcription-polymerase chain reaction. Soothing liver mixture can alleviate hepatocyte injury, effectively improve liver function in rats, attenuate oxidative stress and inflammatory reactions in the body, reduce plasma endotoxin content and inhibit hepatic toll-like receptor-4 and nuclear factorkappa B microRNA and protein expression, the higher the drug dose, the better the silymarin was similar to the high dose soothing liver mixture efficacy. Soothing liver mixture has a better protective effect on rats with liver injury induced by antituberculosis drugs; the mechanism may involve the regulation of plasma endotoxin/toll-like receptor-4/nuclear factor-kappa B signaling pathway the alleviation of the body's oxidative stress and inflammatory reaction. [ABSTRACT FROM AUTHOR]

Background: Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection. Methods: We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018. Results: A total of 1,014 patients were enrolled. The leading culprit drug category was antimicrobials (481, 47.4%), followed by nonsteroidal anti-inflammatory drugs, anticonvulsants, and statins. Among the antimicrobials, antituberculosis agents were most likely to induce liver injury (257, 25.3%), followed by antibacterial, antifungal, and antiviral agents. The liver-related mortality rate was 8.2% (83/1,014). The patients who died had higher rates of hepatocellular-type liver injury, elevated liver biochemical tests, preexisting liver cirrhosis, jaundice, chronic HBV infection, and antituberculosis drug-induced liver injury (ATDILI) than the survivors. A total of 131 patients (12.9%) with DILI were HBV carriers, of whom 23 (17.6%) died of hepatic failure. The rate of HBV-DNA > 2000 IU/mL was higher in the patients who died (47.8% vs. 26.9%, p = 0.047) than in the survivors. After adjusting for possible risk factors, active HBV infection with HBV-DNA > 2000 IU/mL was the most significant risk factor for liver-related mortality (adjusted HR, 4.40, 95% CI, 2.31%-8.38%, p < 0.001). The other independent risk factors for mortality were ATDILI and albumin-bilirubin (ALBI) score (adjusted HR, 1.25 and 4.09, respectively, p < 0.003). Conclusion: Antituberculosis agents were the leading cause of DILI in Taiwanese, and they were associated with poorer outcomes than other drug categories. Active HBV infection, ATDILI and ALBI score were independent risk factors for fatal DILI. Close monitoring of liver tests and timely antiviral therapy should be implemented in HBV carriers during the administration of high-risk drugs, such as antituberculosis agents. [ABSTRACT FROM AUTHOR]

8-Nitro-1,3-benzothiazin-4-ones are a promising class of new antitubercular agents, two candidates of which, namely BTZ043 and PBTZ169 (INN: macozinone), have reached clinical trials. The crystal and molecular structures of two synthetic precursors, 2-chloro-3-nitro-5-(trifluoromethyl)benzoic acid, C8H3ClF3NO4 (1), and 2-chloro-3-nitro-5-(trifluoromethyl)benzamide, C8H4ClF3N2O3 (2), are reported. In 1 and 2, the respective carboxy, carboxamide and the nitro groups are significantly twisted out of the plane of the benzene ring. In 1, the nitro group is oriented almost perpendicular to the benzene ring plane. In the crystal, 1 and 2 form O—H...O and N—H...O hydrogen-bonded dimers, respectively, which in 2 extend into primary amide tapes along the [101] direction. The trifluoromethyl group in 2 exhibits rotational disorder with an occupancy ratio of 0.876 (3):0.124 (3).

Introduction: Antituberculosis drugs are associated with hepatic and renal toxicities due to drug’s radical metabolites. Kleinhovia hospita L extract possesses a potent antioxidant capacity that can be beneficial in eradication of oxidative-induced cell damage. This study aimed to evaluate the effects of K. hospita hydro-alcoholic extract on biomarkers and structure changes in liver and kidney induced by a combination of antituberculosis drugs (CAD), comprising isoniazid, rifampicin, pyrazinamide and ethambutol in Wistar rats. Methods: Thirty-five male Wistar rats were assigned into one of the five groups: control, CAD, and CAD with K. hospita extract in three different doses (125, 250 and 500 mg/kg). The extract was administered three hours prior to CAD and all treatments were carried out for 28 days. Following the last day of treatment, blood samples and organs were collected for biomarker analysis and histopathological examinations. Results: Twenty-eight days of CAD treatment in rats induced marked elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum creatinine and urea levels compared to controls. K. hospita extract at higher doses (250 mg/kg and 500 mg/kg) significantly improved ALT, urea and creatinine levels in the rats treated with CAD (P

BackgroundPregnant women are a common group of people with tuberculosis,especially in patients infected with HIV at the same time. Antituberculosis drug prophylaxis is effective in reducing tuberculosis infection in pregnant women and fetuses after pregnancy, but its safety is still worthy of in-depth discussion. In this study, we conducted a systematic review and meta-analysis of reports on the use of antituberculosis drugs during pregnancy in recent years to provide evidence for clinical diagnosis and treatment.MethodsThe PubMed, Embase, Web of Science databases, Ovid, and clinicaltrials.gov were searched. Search for clinical randomized controlled studies and cohort studies on the use of antituberculosis drugs during pregnancy published in the databases from January 2000 to September 2021 was performed using the Stata 16.0 software after screening qualified bodies of literature.ResultsOn the basis of the initial search of 408 articles, this study included a total of 8 articles and 2,563 patients after screening; meta-analysis results showed that preventive treatment with antituberculosis drugs did not increase the incidence of serious maternal adverse events [RR = 0.99, 95% CI (.88, 1.12), Z = −0.108, P = 0.914], did not increase drug hepatotoxicity [RR = 1.13, 95% CI (.9, 1.43), Z = 1.071, P = 0.284], did not increase the incidence of peripheral nerve disease [RR = 1.52, 95% CI (.85, 2.71), Z = 1.412, P = 0.158], did not increase maternal mortality [RR = 0.67, 95% CI (.27, 1.7), Z = −0.84, P = 0.401], and could significantly reduce adverse pregnancy outcomes [RR = 0.78, 95% CI (0.68, 0.89), Z = −3.581, P < 0.0001].DiscussionThe use of antituberculosis drugs for preventive treatment during pregnancy is safe and can obtain better pregnancy outcomes.

The hepatoprotective activity of remaxol, reamberin and ademethionine was studied on a model of the liver Injury Induced by antituberculosis drugs. The study included 30 male uninbred albino rats. The following antituberculosis drugs were used: isoniazid (50 mg/kg) subcutaneously + rifampicin (250 mg/kg) intragastrically + pyrazinamide (45 mg/kg) intragastically (by the procedure of Yu.I. Slivka, 1989). Remaxol, reamberin and ademethionine were administered 1.5 hour prior to the antituberculosis drugs. The treatment course was 14 days. It was shown that remaxol, reamberin and ademethionin were able to correct the structural and functional disorders in the liver due to the use of the antituberculosis drugs. By the impact on the biochemical indices, evident of the liver function condition, remaxol showed the maximum effect. The effect of reamberin was somewhat lower and the results of the ademethionine use were less significant. Remaxol had also a distinct effect as for lowering the level of the structural injuries in the liver, evident from recovery of the organ histoarchitectonics, less extended carbohydrate, albuminous and fatty degeneration, more active intracellular regeneration. It was noted that ademethionine had an insignificant effect on necrobiosis. Moreover, there was once detected a large necrosis focus, evident of possible stimulation of the liver tissue alteration by the drug.

The efficacy of reamberin, remaxol, S-adenosyl-L-methionine (ademethionine) and 5% glucose solution was estimated in the treatment of patients with tuberculosis of the respiratory organs and drug hepatotoxicity signs confirmed by higher activity of liver indicative enzymes and nitrogen oxide levels. Remaxol showed a pronounced positive effect on the cytolytic syndrome signs, evident from lower activity of alanine aminotransferase and aspartate aminotransferase. At the same time ademethionine was superior to remaxol in the effect on the cholestatic signs and inferior in the effect on the cytolytic signs. By the effect on the activity of alanine aminotransferase and aspartate aminotransferase, reamberin was inferior to remaxol and superior to ademethionine, its effect on the cholestasis markers level vs. the other drugs being superior only to that of 5% glucose solution. As compared to reamberin, ademethionine and 5% glucose solution, remaxol promoted higher integral indices of the host antioxidant protection (total antioxidant capacity and total antioxidant status), that partially explained the drug pronounced hepatoprotective effect.

At present, the conception of the use, efficacy and safety of hepatotropic agents in treatment of drug-induced liver injury, in particular due to antituberculosis drugs is not yet final, which is conditioned by extremely rare clinical trials on the subject adequate to the up-to-date principles of the conclusive medicine. The review presents data on the hepatotoxic effect of antituberculosis drugs, analysis and systematization of the data on the use of hepatotropic agents in liver injury induced by antituberculosis drugs, the principles and characteristics of their clinical use. The mechanism of action of remaxol, a new original hepatotropic agent and the indications of its use are discussed. The experimental findings on the remaxol ability to decrease the antituberculosis drug-induced liver injury through lowering the carbohydrate, albuminous and fatty degeneration and activating the organ reduction are presented. The clinical trials are evident of the most efficient action of remaxol on the signs of toxemia, as well as cytolysis and cholestasis, which along with its antiasthenic and antidepressant action allows to use remaxol as an universal hepatotropic agent in the treatment of diverse drug-induced liver injuries in both the therapeutic and prophylactic schemes.

Preclinical and clinical investigations of levofloxacin in complex with antituberculosis drugs of the main and reserve groups in 152 patients with newly diagnosticated drug resistant pulmonary tuberculosis demonstrated its efficacy and safety. The adverse events due to levofloxacin (8.6% of the cases) disappeared after discontinuation of the drug use without any affection of the patient's organs. Levofloxacin is applicable in antituberculosis therapy of patients with extended, acute progressing or polycavernous tuberculosis of the lungs. It provides significant clinical improvement and if necessary allows to prepare the patient in a short period for surgical operation.

Pharmacokinetic parameters of PAS-Akri coated tablets (Akrikhin, Russia) were investigated. The tablets contain paraaminosalicylic acid (PAS) as sodium dihydrate in an amount of 1000 mg. The single oral dose of the drug for healthy volunteers in the trial was 6, 9 or 12 tablets. In 7 days the dosage was changed. The blood samples were collected 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 10 hours after the drug administration. The PAS serum levels were determined with HPLC. The trials will allow to optimize the dosing of PAS for providing efficient antituberculosis therapy.

Efficient chemotherapy of tuberculosis patients could be complicated by hepatoprotective responses to antituberculosis drugs. The frequency and nature of the response depend on the drug and the genotypical and phenotypical characteristics of its metabolism in the patients, that should be considered while choosing the hepatoprotector. The liver injury was induced by the reserve antituberculosis drugs in experiments on rats with various acetylation phenotypes. Analysis of the clinicobiochemical and morphological indices revealed differences in the liver injury simulation: prevalence of the cytolytic mechanism in slow acetylators vs. the rapid ones.

In spite of the availability of many antituberculosis drugs all over the world the morbidity of tuberculosis does not lower. Often the tuberculosis therapy schemes are adapted to every particular patient which is mainly due to the therapy unfavourable effects requiring discontinuation of the drugs used. Polymorphism of the detoxication genes, as predictors of the response to the drug therapy, was shown to be of certain significance. The experimental data would allow to substantiate personalized management of tuberculosis patients and to increase its efficacy and safety.

DRESS syndrome is defined as drug-induced hypersensitivity syndrome with rash, eosinophilia, and systemic symptoms. This syndrome is mostly associated with anticonvulsants, antibacterial and anti-inflammatory drugs. DRESS syndrome is a rare disease and is more frequently seen in adults. We present the first case report of DRESS syndrome in an 8-year-old girl, after 3 months of treatment with isoniazid and rifampicin. After discontinuation of drugs and a short course of prednisolone the girl recovered. After 5 years of follow-up, she is healthy and has no complaints but patch tests with isoniazid and rifampicin remain positive. The reported case emphasizes the importance of thorough medical history and including drug reactions in differential diagnosis.

A 44-year-old woman underwent a follow-up examination for Crohn's disease 9 years ago. Chest computed tomography (CT) showed an infiltration shadow with a cavity in the right upper lobe. After a CT-guided lung biopsy, epitheloid granuloma was noted, and an acid-fast bacilli examination was smear-positive, but a culture examination was negative. Because the abnormal chest shadow with cavity gradually increased and right shoulder pain appeared, we performed bronchoscopy again six months later. Mycobacterium heckeshornense was isolated from the bronchoalveolar lavage fluid specimen, so we diagnosed her with pulmonary M. heckeshornense disease. Isoniazid, rifampicin, and ethambutol were administered, and the abnormal chest shadow improved.

A 31-year-old male patient presented with sudden onset loss of vision in the left eye. Ocular examination revealed significant vitritis with chorioretinitis lesion in the posterior pole. Subsequent investigations revealed positive human immunodeficiency virus (HIV) and syphilis serology; chest imaging revealed active pulmonary tuberculosis. Polymerase chain reaction from aqueous aspirate was positive for Mycobacterium tuberculosis. There was complete resolution of the lesions following antisyphilitic medications, antitubercular therapy along with highly active antiretroviral therapy. Syphilis and tuberculosis coinfection in a previously unknown HIV patient is rare but can occur. It is worthwhile to look for multiple coinfections in HIV patients.

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia. [ABSTRACT FROM AUTHOR]

Aim: Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients. Methods: A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models. Results: In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low‐weight bands. Simulations also showed significantly lower drug exposures in low‐weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration‐time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed‐dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low‐weight bands. Conclusion: PK variability of first‐line anti‐TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment. [ABSTRACT FROM AUTHOR]

The aim. To conduct a structural analysis of the volume of government spending on the purchase of antituberculosis drugs (anti-TB D) within 2014-2018. Materials and methods. In the study, we used information on public procurement of anti-TB D for 2014-2018 presented on the website of the Ministry of Health of Ukraine in the section "Procurement of Medicines", as well as statistical data of the "Center for Public Health of the Ministry of Health of Ukraine" on the incidence of multi-drug resistant tuberculosis (MDR-TB) in the population. Analytical and comparative, system, and logical methods, as well as economic analysis were used. With the help of synthesis the conclusions and recommendations were formed. Results. It was found that in 2014-2018, the MDR-TB incidence rate increase had a positive dynamics in reducing the number of registered cases. For example, in 2015 this indicator was 2.56 %, and in 2018 it was -7.93 %. It was proven that public procurement of anti-TB D in physical terms was chaotic. Thus, in 2015/2014, the growth rate of anti-TB D number was 35.55 %, in 2016/2015 - 31.59 %, in 2017/2016 - 15.31 %, in 2018/2017 - 6.13 %. It was found that the dynamics of the growth rate of purchases of TB D in the national currency and USD had some differences. For example, in 2015, expenses increased by 55.02 % in the national currency, while in dollar terms this indicator decreased by 15.64 % compared to 2014. At the same time, in 2018 there was a positive trend of increasing the volume of public spending in monetary terms. Thus, in 2018, the growth rate in the national currency was 53.16 %, and in USD - 49.83 %. It was found that in the structure of public spending there was a tendency for an insignificant predominance of foreign anti-TB D. Based on the comparative analysis of government spending on groups of anti-TB D by the priority of their use in treatment regimens according to the standards it was determined that the process of anti-TB D purchasing did not meet the priority criteria for treatment. It complicates the implementation of the process of reforming TB care in connection with the construction of an outpatient model. Conclusions. The results of the analysis indicate that there is a need to make a number of organizational and economic decisions to increase the level of availability of anti-TB D in the treatment of patients with MDR-TB. Critical measures include monitoring procurement programs based on real regional needs taking into account disease indicators. In addition, it is relevant to review the lists of drugs that are purchased with priority regarding the inclusion of drugs of domestic production, which belong to the second line anti-TB D in pharmacotherapy regimens. The list of measures also includes monitoring of prices taking into account inflationary processes in the state and predicting their impact on the volume of public spending on the purchase of anti-TB D. [ABSTRACT FROM AUTHOR]

8-Nitro-1,3-benzothiazin-4-ones are a promising class of new antitubercular agents, two candidates of which, namely BTZ043 and PBTZ169 (INN: macozinone), have reached clinical trials. The crystal and molecular structures of two synthetic precursors, 2-chloro-3-nitro-5-(trifluoromethyl)benzoic acid, C8H3ClF3NO4 (1), and 2-chloro-3-nitro-5-(trifluoromethyl)benzamide, C8H4ClF3N2O3 (2), are reported. In 1 and 2, the respective carboxy, carboxamide and the nitro groups are significantly twisted out of the plane of the benzene ring. In 1, the nitro group is oriented almost perpendicular to the benzene ring plane. In the crystal, 1 and 2 form O-H...O and N-H...O hydrogen-bonded dimers, respectively, which in 2 extend into primary amide tapes along the [101] direction. The trifluoromethyl group in 2 exhibits rotational disorder with an occupancy ratio of 0.876 (3):0.124 (3). [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Sefako Makgatho Health Sciences University.)