rifampin and Diabetes-Mellitus--Type-2

Rifampicin plays a key role in the management of prosthetic joint infections (PJIs); however, the emergence of rifampicin resistance is associated with less favourable clinical outcomes. The purpose of this study was to investigate the impact of rifampicin resistance and other patient-related factors on recovery rates among patients with PJI undergoing two-stage revision.. We reviewed medical records and microbiology reports of 73 patients (41 males and 32 females) undergoing two-stage revision due to PJI between 2017 and 2019. Patient-specific data, comorbidities and the antibiotic resistance of microbiological isolates were registered. Forty-eight patients had hip, 22 had knee, 2 had shoulder and 1 had elbow joint infection. Obtained data were statistically analysed with a logistic regression model.. Rifampicin-sensitive organism was isolated in 53 cases (72.6%). Recovery rate was 92.5% in the sensitive and 60.0% in the resistant group. We observed that rifampicin resistance significantly reduced the probability of recovery. Furthermore, in the rifampicin-sensitive group, the probability of recovery decreased with advancing age with a significant drop above the age of 60 years. The effect of age is negligible in the rifampicin-resistant group. We also found that type 2 diabetes mellitus has a negative effect on recovery. Coagulase-negative Staphylococci were predominant in the rifampicin-sensitive (50% of the isolates) and Gram-negative rods in the resistant group (40%).. Rifampicin resistance was associated with lower recovery rates among patients undergoing two-stage revision due to PJI. Higher age and type 2 diabetes mellitus had negative impact on clinical outcome.

Topics: Arthroplasty, Replacement, Hip; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Prosthesis-Related Infections; Rifampin; Risk Factors

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

This study aimed to explore the relationship between glycosylated hemoglobin (HbA1c) and the risk of anti-tuberculosis (TB) drug resistance for TB-type 2 diabetes mellitus (T2DM) patients.. From March 2014 to June 2019, medical records from multiple centers were searched. Logistic regression analyses were performed. A predictive model for multidrug-resistance (MDR) was developed and validated. Calibration and discrimination of the model were assessed.. Inconsistent results were found in the systemic review. A multicenter chart review with 657 records was thus conducted. The HbA1c <7% group and HbA1c ≥7% group had 390 and 267 patients, respectively. The HbA1c<7% group had a lower risk of developing rifampicin resistance, isoniazid resistance and MDR, with odd ratios (ORs) of 1.904 (p=0.001), 2.896 (p<0.001) and 3.228 (p<0.001), respectively. The between-group differences in the risk of anti-TB drug resistance were analyzed based on data from three provinces in China. After adding HbA1c grading, the predictive model for MDR (https://mengyuan.shinyapps.io/Shinyapp/) showed excellent capacity with an AUC of 75.4% in the training set (Sichuan and Gansu) and 73.9% in the internal validation set (Henan). The performances in calibration, prediction probabilities and net clinical benefit were significantly improved by HbA1c grading.. HbA1c grading was an independent risk factor for isoniazid resistance and MDR in TB-T2DM patients.

Topics: Adult; Aged; Antitubercular Agents; Diabetes Mellitus, Type 2; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Glycated Hemoglobin; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Odds Ratio; Rifampin; Risk Factors; Tuberculosis; Tuberculosis, Multidrug-Resistant

Optimal management of combined tuberculosis (TB) and diabetes (DM) is important but challenging in terms of achieving good disease outcomes and avoiding toxicity, drug interactions and other challenges. DM management during anti-tuberculosis treatment, aimed at improving TB treatment outcomes and reducing DM-related morbidity and mortality, consists of glycaemic control and measures to reduce the risk of cardiovascular disease. Metformin, the glucose-lowering drug of choice for TB patients, has no meaningful interaction with rifampicin (RMP), and may reduce TB mortality. Insulin is effective for severe hyperglycaemia, but has several disadvantages that limit its use in TB patients. Cardiovascular risk assessment should be considered in TB-DM patients to guide management in terms of counselling and prescription of antihypertensive, lipid-lowering and anti-platelet treatment. With regard to anti-tuberculosis treatment, DM is associated with an increased risk of drug resistance, lower exposure to anti-tuberculosis drugs, treatment failure and recurrent TB. Patients therefore need careful assessment before, during and possibly after anti-tuberculosis treatment. Although no studies have been performed, anti-tuberculosis treatment may also have to be prolonged or intensified in terms of regimen or drug dosage if DM is present. With regard to service delivery, combined treatment should probably be administered, supervised and monitored as much as possible in a TB clinic. Local circumstances and severity of DM will guide the need for referral of patients to specialised DM care, and continuation of DM care after completion of anti-tuberculosis treatment. More data are also needed for the management of TB-DM patients with human immunodeficiency virus co-infection.

Topics: Antitubercular Agents; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Hypoglycemic Agents; Metformin; Recurrence; Rifampin; Risk Assessment; Treatment Outcome; Tuberculosis

BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Epidural Abscess; Humans; Laminectomy; Lumbar Vertebrae; Male; Middle Aged; Rifampin; Risk Factors; Schizophrenia; Spinal Stenosis; Staphylococcal Infections; Suction; Treatment Outcome; Vancomycin

Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology.

Topics: Aging; Amyloid; Amyloid beta-Peptides; Animals; Cell Death; Copper; Diabetes Mellitus, Type 2; Heparin; Humans; Hydrogen-Ion Concentration; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Mice; Mutation; Nondisjunction, Genetic; Proprotein Convertase 2; Rats; Rifampin

Repaglinide is a novel, fast-acting prandial oral hypoglycaemic agent developed for the treatment of patients with type 2 diabetes whose disease cannot be controlled by diet and exercise alone. Although repaglinide binds to the sulphonylurea binding sites on pancreatic beta-cells and has a similar mechanism of action, repaglinide exhibits distinct pharmacological properties compared with these agents. Following administration, repaglinide is absorbed rapidly and has a fast onset of dose-dependent blood-glucose lowering effect. The drug is eliminated rapidly via the biliary route, without accumulation in the plasma after multiple doses. Repaglinide is well tolerated in patients with type 2 diabetes, including elderly patients and patients with hepatic or renal impairment. The pharmacokinetic profile of repaglinide and the improvements in post-prandial hyperglycaemia and overall glycaemic control make repaglinide suitable for administration preprandially, with the opportunity for flexible meal arrangements, including skipped meals, without the risk of hypoglycaemia.

Topics: Adult; Aged; Blood Glucose; Carbamates; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Hypoglycemic Agents; Liver Diseases; Male; Piperidines; Renal Insufficiency; Rifampin

Seventeen cases of infections due to Cunninghamella species have been reported worldwide in humans, and there have been only three survivors. We report a case of paranasal sinusitis due to Cunninghamella bertholletiae in an elderly patient who had diabetes mellitus and myelodysplasia. After receiving 7 weeks of therapy with deoxycholate amphotericin B (44 mg/kg or a total of 3 g) and rifampin, the patient was cured and did not have to undergo radical surgery.

Topics: Aged; Amphotericin B; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Ethmoid Sinusitis; Humans; Male; Maxillary Sinusitis; Mucorales; Mucormycosis; Myelodysplastic Syndromes; Paranasal Sinuses; Rifampin; Tomography, X-Ray Computed

Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).. The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.. PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.. ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

Topics: Adult; Antitubercular Agents; Cohort Studies; Diabetes Mellitus, Type 2; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifampin; Tanzania

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

Piragliatin is a CYP3A substrate; its inactive metabolite M4, formed through cytosolic reductase, is reversibly metabolized back to piragliatin through CYP3A. The impact of concomitant CYP3A modifiers thus cannot be predicted. Drinking alcohol under fasting conditions is associated with a recognized glucose-lowering effect, which might be synergistic with piragliatin's hypoglycemic effect. Two exploratory studies were conducted to examine these potential interactions in type 2 diabetes (T2D) patients: 16 completed an open-label, sequential 2-way crossover, 2-arm (randomized to ketoconazole and rifampicin) CYP3A study; another 18 participated in a double-blind, placebo-controlled, randomized 3-way crossover ethanol study. Administration of piragliatin (100-mg single dose) resulted in a 32% Cmax and 44% area under the curve (AUC∞ ) increase in piragliatin exposure without affecting glucose AUC0-6h following ketoconazole (400 mg QD × 5 days); 30% Cmax and 72% AUC∞ decrease in piragliatin exposure with a 13% increase in glucose AUC0-6h following rifampicin (600 mg QD × 5 days); and, unexpectedly, a 32% Cmax and 23% AUC0-6h decrease (no change in AUC∞ ) in piragliatin exposure with a 13% increase in glucose AUC0-6h following alcohol (40-g single dose). In conclusion, a strong CYP3A modifier or concomitant alcohol could lead to a change in exposure to piragliatin with a potential alteration in glucose-lowering effect.

Topics: Adult; Aged; Benzeneacetamides; Blood Glucose; Cross-Over Studies; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Diabetes Mellitus, Type 2; Double-Blind Method; Ethanol; Female; Humans; Hypoglycemic Agents; Ketoconazole; Male; Middle Aged; Rifampin

To observe the clinical effect on type 2 diabetes mellitus (T2DM) complicated with pulmonary tuberculosis (TB) of insulin, isoniazid, rifampicin, pyrazinamide and ethambutol (conventional medication) administered together with Qi-boosting and Yin-nourishing decoction derived from Traditional Chinese Medicine (TCM).. A total of 60 patients with T2DM complicated with pulmonary TB were randomly and equally divided into positive control group and treatment group. The control group was treated with Western conventional regiment (WCR): insulin, isoniazid, rifampicin, pyrazinamide, and ethambutol, whereas the treatment group was given both WCR and Qi-boosting and Yin-nourishing decoction prepared from TCM.. After the treatment, 20 (66.7%) and 11 (36.7%) cases showed sputum bacteria negative conversion in the WCR plus TCM group and WCM group respectively (P < 0.05). A total of 25 (83.3%) and 18 (60%) cases showed improvement in lung lesion in the WCR plus TCM group and WCM group respectively (P < 0.05). Compared with WCR group, fasting plasma glucose and 2-hour postprandial blood glucose levels in the WCR plus TCM group significantly decreased (P < 0.05 and P < 0.01, respectively).. Qi-boosting and Yin-nourishing decoction combined with the Western medication showed better curative effect in treating T2DM complicated with pulmonary TB compared with the group using the conventional Western Medicine alone.

Topics: Adult; Aged; Antitubercular Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drugs, Chinese Herbal; Ethambutol; Female; Humans; Hypoglycemic Agents; Insulin; Isoniazid; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

Dapagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that decreases serum glucose by reducing renal glucose reabsorption, thereby promoting urinary glucose excretion. Dapagliflozin is primarily metabolized via the uridine diphosphate-glucuronosyltransferase (UGT)1A9 pathway to its major inactive metabolite, dapagliflozin 3-O-glucuronide. The aim of this study was to evaluate the potential for drug-drug interaction between dapagliflozin and two potential UGT1A9 modulators.. The results of two open-label, non-randomized, single-sequence studies are reported in which the effects of rifampin (a pleiotropic drug-metabolizing enzyme inducer; study 1) and mefenamic acid (a strong UGT1A9 inhibitor; study 2) were evaluated on the pharmacokinetics and pharmacodynamics (assessed by urinary glucose excretion [UGE]) of dapagliflozin in healthy subjects. In study 1, 14 subjects received single doses of dapagliflozin 10 mg alone and in the presence of rifampin 600 mg QD (6 days). In study 2, 16 subjects received single doses of dapagliflozin 10 mg alone and in the presence of mefenamic acid 250 mg q6h (5 days).. Rifampin reduced total exposure (area under the concentration-time curve from time 0 to infinity [AUC0-inf]) to dapagliflozin by 22% and mefenamic acid increased dapagliflozin AUC0-inf by 51%. No clinically meaningful effect of rifampin or mefenamic acid on the pharmacokinetics of dapagliflozin or on dapagliflozin-mediated urinary glucose excretion was observed.. Modest changes in dapagliflozin exposure were seen with rifampin and mefenamic acid with minor changes in UGE, none of which were considered clinically meaningful.

Topics: Adolescent; Adult; Benzhydryl Compounds; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Female; Glucosides; Glucuronosyltransferase; Humans; Hypoglycemic Agents; Male; Mefenamic Acid; Middle Aged; Rifampin; Signal Transduction; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; UDP-Glucuronosyltransferase 1A9

PB-201 is the second glucokinase activator in the world to enter the phase III clinical trials for the treatment of type 2 diabetes mellitus (T2DM). Combined with the efficacy advantages and the friendly absorption, distribution, metabolism, and excretion characteristics, the indication population of PB-201 will be broad. Because the liver is the primary organ for PB-201 elimination, and the elderly account for 20% of patients with T2DM, it is essential to estimate PB-201 exposure in specific populations to understand the pharmacokinetic characteristics and avoid hypoglycemia. Despite the limited contribution of CYP3A4 to PB-201 metabolism in vivo, the dual effects of nonspecific inhibitors/inducers on PB-201 (substrate for CYP3A4 and CYP2C9 isoenzymes) exposure under fasted and fed states also need to be evaluated to understand potential risks of combination therapy. To grasp the unknown information, the physiologically-based pharmacokinetic (PBPK) model was first developed and the influence of internal and external factors on PB-201 exposure was evaluated. Results are shown that the predictive performance of the mechanistic PBPK model meets the predefined criteria, and can accurately capture the absorption and disposition characteristics. Impaired liver function and age-induced changes in physiological factors may significantly increase the exposure under fasted state by 36%-158% and 48%-82%, respectively. The nonspecific inhibitor (fluconazole) and inducer (rifampicin) may separately increase/decrease PB-201 systemic exposure by 44% and 58% under fasted state, and by 78% and 47% under fed state. Therefore, the influence of internal and external factors on PB-201 exposure deserves attention, and the precision dose can be informed in future clinical studies based on the predicted results.

Topics: Aged; Computer Simulation; Cytochrome P-450 CYP3A; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Models, Biological; Rifampin

BACKGROUND Foot ulcers are high-morbidity and debilitating complications of diabetes mellitus, and carry significantly increased rates of associated major amputations. They contribute to significantly worse quality of life. Osteomyelitis is a frequent complication of diabetic foot ulcers, since bacteria can contiguously spread from soft tissues to the bone, involving the cortex first and then the bone marrow. Unfortunately, clinically unsuspected osteomyelitis is frequent in persisting diabetic foot ulcers. It is associated with limb amputations and increased mortality. CASE REPORT We describe a 76-year-old man with long-standing insulin-treated type 2 diabetes, who experienced extensively drug-resistant Enterococcus faecalis diabetic foot myositis and osteomyelitis associated with sepsis. He was successfully treated with surgical debridement combined with the administration of teicoplanin plus rifampicin in the outpatient setting, completing, in total, a twelve-week course of antibiotic therapy. CONCLUSIONS Clinically unsuspected osteomyelitis in patients with persisting diabetic foot ulcers has been associated with infections from highly resistant bacteria. Early and accurate diagnosis of diabetic foot osteomyelitis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diabetic Foot; Enterococcus faecalis; Humans; Male; Myositis; Osteomyelitis; Outpatients; Pharmaceutical Preparations; Quality of Life; Rifampin; Teicoplanin

Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed.. The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations.. The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.

Topics: Antitubercular Agents; Diabetes Mellitus, Type 2; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Phylogeny; Polymorphism, Single Nucleotide; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant; Whole Genome Sequencing

Rifampicin is one of the most important drugs for the treatment of tuberculosis (TB). Polymorphisms in SLCO1B1 and SLC10A1 genes are associated with impaired transporter function of drug compounds such as rifampicin. The relationship between genetic variation, clinical comorbidities, and rifampicin exposures in TB patients has not been completely elucidated. The aim of this study was to investigate the prevalence of SLCO1A1 and SLCO1B1 polymorphisms in TB and TB-DM patients and to determine their relationship with rifampicin pharmacokinetics on patients from México. Blood samples were collected in two hospitals in Baja California, Mexico from February through December 2017. Sampling included 19 patients with TB, 11 with T2DM and 17 healthy individuals. Polymorphisms genotype rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs72559746,rs2291075 and rs4603354 of SLCO1B1 and rs4646285 and rs138880008 of SLC10A1 were analyzed by Sanger's sequencing. None of the SLCO1B1 and SLC10A1 variants were significantly associated with rifampicin C

Topics: Diabetes Mellitus, Type 2; Genotype; Humans; Liver-Specific Organic Anion Transporter 1; Mexico; Morbidity; Mycobacterium tuberculosis; Organic Anion Transporters, Sodium-Dependent; Polymorphism, Single Nucleotide; Rifampin; Symporters; Tuberculosis

Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics.. An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference.. Rifampicin decreased the AUC

Topics: Antiviral Agents; Area Under Curve; Cross-Over Studies; Cytochrome P-450 CYP3A; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Interactions; Healthy Volunteers; Humans; Hypoglycemic Agents; Piperazines; Protease Inhibitors; Rifampin

The therapeutic success of peptidic GLP-1 receptor agonists for treatment of type 2 diabetes mellitus (T2DM) motivated our search for orally bioavailable small molecules that can activate the GLP-1 receptor (GLP-1R) as a well-validated target for T2DM. Here, the discovery and characterization of a potent and selective positive allosteric modulator (PAM) for GLP-1R based on a 3,4,5,6-tetrahydro-1

Topics: Allosteric Regulation; Animals; Blood Glucose; Cells, Cultured; Diabetes Mellitus, Type 2; Drug Design; Glucagon-Like Peptide-1 Receptor; HEK293 Cells; Humans; Hypoglycemic Agents; Male; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Rats; Rats, Sprague-Dawley

The pharmacokinetic (PK) and clinical implications of combining metformin with rifampicin are relevant to increasing numbers of patients with diabetic tuberculosis (TB) across the world and are yet unclear. We assessed the impact of rifampicin on metformin PKs and its glucose-lowering effect in patients with diabetic TB by measuring plasma metformin and blood glucose during and after TB treatment. Rifampicin increased metformin exposure: plasma area under the plasma concentration-time curve from time point 0 to the end of the dosing interval (AUC

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Drug Interactions; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Rifampin; Tuberculosis; Young Adult

Metformin (MET) is a potential combination drug to elevate anti-TB efficacy. However, the clinical effect, especially smear reversion, during metformin applied with anti-tuberculosis and insulin in patients with type 2 DM newly TB co-infection were remain unknown. An observational clinical study was done in DM newly TB co-infection outpatients at Surabaya Paru Hospital. This study evaluated MET therapy, at least 2 months, accompanying with insulin and anti-TB regimens and compared to comparison group. The smear, microtubule-associated Protein1 Light Chain 3B (MAP1LC3B) level, as the presentation of autophagy, Superoxide Dismutase (SOD) level, Interferon (IFN)-γ and Interleukin (IL)-10 levels were evaluated twice. From 42 participants in this study, 22 participants of observation group that received additional MET therapy, 100% had sputum smear reversion after 2-months intensive phase of anti-TB therapy. Whereas 25% of 20 participants of comparison group did not undergo reversion inserts sputum smear. As conclusion, MET has the potential of being an additive combination therapy to enhance the bactericidal effect of anti-TB on DM-TB coinfection patients. Metformin enhances the effects of anti-TB and insulin therapy in increasing the smear reversion by increasing autophagy.

Topics: Adult; Antitubercular Agents; Autophagy; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Ethambutol; Humans; Hypoglycemic Agents; Insulin; Interferon-gamma; Interleukin-10; Isoniazid; Leukocytes, Mononuclear; Metformin; Microtubule-Associated Proteins; Middle Aged; Pyrazinamide; Rifampin; Sputum; Superoxide Dismutase; Tuberculosis

Topics: Aged, 80 and over; Diabetes Mellitus, Type 2; Doxycycline; Echocardiography; Electroencephalography; Embolism; Endocarditis; Fever; Fluorodeoxyglucose F18; Heart Valve Prosthesis; Humans; Hypertension; Magnetic Resonance Imaging; Male; Myocardial Infarction; Positron Emission Tomography Computed Tomography; Rifampin; Treatment Outcome

Sulfonylureas (SUs) such as glibenclamide, gliclazide, glimepiride, glipizide and gliquidone are one of the first oral medicines available for the treatment of type 2 diabetes and are widely used for the treatment of hyperglycaemia. The hepatic transporters, organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), play an important role in the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. Drug-drug interactions mediated by OATP1B1/1B3 may result in the hepatic transporting change for drug substrates. The inhibitory effects of glibenclamide and glimepiride on sulfobromophthalein (BSP) uptake have been previously studied, and glibenclamide has been reported as the substrate of OATP1B3, but it remains unclear whether other SUs such as gliclazide, glipizide and gliquidone are substrates of OATP1B1 and OATP1B3. Here, we investigated the relationship between the five most commonly applied SUs (glibenclamide, gliclazide, glimepiride, glipizide, gliquidone) and OATP1B1 and OATP1B3. We performed uptake and inhibition assays in HEK293T cells stably expressing OATP1B1 or OATP1B3, respectively, and established a liquid chromatography-mass spectrometry (LC-MS) method for the simultaneous measurement of five SUs. We demonstrated that gliclazide and glimepiride are substrates of OATP1B1 and glibenclamide and glipizide are substrates of OATP1B3. We also confirmed the interaction between these SUs and rosuvastatin. No transporting was observed for gliquidone, suggesting that it is not a substrate of either transporter.

Topics: Diabetes Mellitus, Type 2; Drug Interactions; Glycyrrhizic Acid; HEK293 Cells; Hepatocytes; Humans; Hypoglycemic Agents; Liver; Liver-Specific Organic Anion Transporter 1; Rifampin; Rosuvastatin Calcium; Solute Carrier Organic Anion Transporter Family Member 1B3; Sulfobromophthalein; Sulfonylurea Compounds; Tandem Mass Spectrometry

In 2015, 10.4 million people developed tuberculosis (TB) and 580,000 amongst them suffered from multidrug-resistant TB (MDR-TB). From those 580,000 cases of MDR-TB, only 125,000 were detected and reported. A total of 111,000 people began to receive MDR-TB treatment in 2014 while 190,000 MDR-TB patients were estimated to have died, largely due to lack of access to effective treatment. The mechanism of drug resistance can be caused by genetic factors, factors related to previous treatment and other factors such as comorbidity with diabetes mellitus. Although there is some evidence which postulate host genetic predisposition is the basis for the development of MDR-TB, changes in the genomic content is the major underlying event in the emergence of variants strains in the M. tuberculosis complex. Spontaneous chromosomally-borne mutation occurring in M. tuberculosis at predictable rates are thought to confer resistance to anti-TB drugs. Factors related to previous anti-tuberculosis treatments consists of incomplete or inadequate treatment and also poor treatment adherence. A review of the published literature strongly suggest that the most powerful predictor for the presence of MDR-TB is a history of TB treatment. Many new cases of MDR-TB are created by physician's errors related to drugs regimen, dosing interval and duration of treatment. Multidrug-resistance TB developed due to error in TB management in the past such as initiation of an inadequat regimen using first line anti-TB drugs, the addition of single drug to a failing regimen, the failure to identify pre-existing resistance and variations in bioavailability of anti-TB drugs that predispose the patient to the development of MDR-TB. Non-adherence to prescribed treatment is often underestimated by physicians and difficult to predict. Certain factors such as psychiatric illness, alcoholism, drug additiction and homelessness can predict non-adherence to treatment. Poor compliance with the treatment is also an important factor in the development of acquired drug resistance.Diabetes mellitus has been a well-known risk factor for TB in the past. The global convergence of the accelerating type 2 DM pandemic, high TB prevalence and drug-resistant TB during the past couple of decades has become a serious challenge to clinicians worldwide. Over the past few years, some studies have shown that the treatment failure rate is higher in TB patients with DM as comorbidity. Moreover, there is significant association be

Topics: Antibiotics, Antitubercular; Diabetes Mellitus, Type 2; Humans; Medication Adherence; Mycobacterium tuberculosis; Rifampin; Risk Assessment; Risk Factors; Tuberculosis, Multidrug-Resistant

Mycobacterium gordonae, a low pathogenicity organism, is rarely implicated in skin and soft tissue infections. We present a 77-year-old returned diabetic traveler from rural Sudan with cutaneous M. gordonae infection. Several months of ciprofloxacin, rifampin and ethambutol led to resolution of his plaque, without signs of recurrence at 6-month follow-up.

Topics: Aged; Anti-Bacterial Agents; Ciprofloxacin; Diabetes Mellitus, Type 2; Diagnosis, Differential; Ethambutol; Humans; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Skin Diseases, Infectious; Travel

Diabetes mellitus (DM) is a well-known risk factor to develop tuberculosis (TB). Some reports indicate the serum concentrations of anti-TB drugs are lower in patients with TB and DM than those with TB only. Therefore, we developed a nonlinear mixed-effects model (NONMEM) to determine the population PK parameters of rifampin and assessed the effects of DM status in patients with TB. One-compartment linear modeling with first-order absorption was evaluated using the 206 plasma samples of rifampin from 54 patients with DM. Based on the final model, DM affected the absorption rate constant (ka) and the volume of distribution (Vd) of rifampin. The body mass index (BMI) of the patients affected rifampin clearance (CL). The ka of rifampin in patients with TB and DM was greater than that in patients with TB only. Further, the predicted Vd in patients with DM was greater than that in patients without DM. As Vd is inversely correlated with plasma concentrations, the rifampin concentrations were predicted to be lower in the patients with DM. The authors recommend administering the greater doses of rifampin for the treatment of TB in patients with DM compared with the doses for the patients without DM to prevent treatment failure.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Models, Chemical; Prospective Studies; Rifampin; Tuberculosis, Pulmonary; Young Adult

Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 2; Female; Half-Life; Humans; Interleukin-17; Killer Cells, Natural; Male; Middle Aged; Rifampin; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Young Adult

Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (P < 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (P < 0.01), 66% or 100% (P < 0.05), 30% or 50% (P = 0.198), and 32% or 21% (P = 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients.

Topics: Adult; Antitubercular Agents; Biological Availability; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Dosage Calculations; Ethambutol; Female; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

Topics: Cicatrix; Clarithromycin; Debridement; Diabetes Mellitus, Type 2; Disease Susceptibility; Femoral Fractures; Fracture Fixation, Internal; Fractures, Closed; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Osteomyelitis; Osteotomy; Ribotyping; Rifampin; Surgical Wound Infection; Vancomycin

At the University Centre for Chronic Diseases Dekkerswald, a tertiary tuberculosis (TB) referral hospital in The Netherlands, therapeutic drug monitoring (TDM) is used in patients in case of relapse TB, when there is delayed response to TB treatment, and when abnormal TB drug concentrations are suspected for other reasons. In this article, a case series is presented to illustrate the value of individualized TB drug dosing in four patients with low TB drug concentrations. Increased doses of the TB drugs, especially of rifampicin, resulted in adequate peak plasma concentrations and improved clinical response to treatment in these patients, while no adverse events occurred.

Topics: Adult; Aged; Alcoholism; Antibiotics, Antitubercular; Antitubercular Agents; Chromatography, High Pressure Liquid; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Monitoring; Ethambutol; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Precision Medicine; Pyrazinamide; Recurrence; Rifampin; Schizophrenia; Sputum; Treatment Failure; Tuberculosis; Tuberculosis, Multidrug-Resistant

Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin.

Topics: Amikacin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow; Bone Marrow Diseases; Ciprofloxacin; Diabetes Mellitus, Type 2; Humans; Isoniazid; Male; Middle Aged; Mycobacterium fortuitum; Mycobacterium Infections, Nontuberculous; Rifampin; Treatment Outcome

Altered pharmacokinetics of antituberculosis drugs may contribute to an increased risk of tuberculosis treatment failure for diabetic patients. We previously found that rifampin exposure was 2-fold lower in diabetic than in nondiabetic tuberculosis patients during the continuation phase of treatment. We now examined the influence of diabetes on the pharmacokinetics of antituberculosis drugs in the intensive phase of tuberculosis treatment, and we evaluated the effect of glycemic control. For this purpose, 18 diabetic and 18 gender- and body weight-matched nondiabetic tuberculosis patients were included in an Indonesian setting. Intensive pharmacokinetic sampling was performed for rifampin, pyrazinamide, and ethambutol at steady state. The bioavailability of rifampin was determined by comparing rifampin exposure after oral versus intravenous administration. Pharmacokinetic assessments were repeated for 10 diabetic tuberculosis patients after glycemic control. No differences in the areas under the concentration-time curves of the drugs in plasma from 0 to 24 h postdose (AUC(0-24)), the maximum concentrations of the drugs in plasma (C(max)), the times to C(max) (T(max)), and the half-lives of rifampin, pyrazinamide, and ethambutol were found between diabetic and nondiabetic tuberculosis patients in the intensive phase of tuberculosis treatment. For rifampin, oral bioavailability and metabolism were similar in diabetic and nondiabetic patients. The pharmacokinetic parameters of antituberculosis drugs were not correlated with blood glucose levels or glucose control. We conclude that diabetes does not alter the pharmacokinetics of antituberculosis drugs during the intensive phase of tuberculosis treatment. The reduced exposure to rifampin of diabetic patients in the continuation phase may be due to increased body weight and possible differences in hepatic induction. Further research is needed to determine the cause of increased tuberculosis treatment failure among diabetic patients.

Topics: Adult; Antitubercular Agents; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Pulmonary

Topics: Aged, 80 and over; Anti-Bacterial Agents; Cardiology; Daptomycin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endocarditis, Bacterial; Female; Humans; Incidental Findings; Interdisciplinary Communication; Lung Neoplasms; Medical Oncology; Pacemaker, Artificial; Patient Care Team; Pulmonary Disease, Chronic Obstructive; Pulmonary Medicine; Radiography; Referral and Consultation; Rifampin; Streptococcal Infections; Streptococcus sanguis; Thoracic Surgery

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Rifampin; Risk Factors; Sensitivity and Specificity; Treatment Outcome; Tuberculosis

Type 2 diabetes (DM) is a strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Because lower concentrations of anti-TB drugs may be a contributing factor, we compared the pharmacokinetics of rifampicin in patients with TB, with and without DM.. Seventeen adult Indonesian patients with TB and DM and 17 age- and sex-matched patients with TB and without DM were included in the study during the continuation phase of TB treatment. All patients received 450 mg of rifampicin (10 mg/kg) and 600 mg of isoniazid 3 times weekly. Steady-state plasma concentrations of rifampicin and its metabolite desacetylrifampicin were assessed at 0, 2, 4, and 6 h after drug intake.. Geometric means of rifampicin exposure (AUC(0-6 h)) were 12.3 mg x h/L (95% confidence interval [CI], 8.0-24.2) in patients with TB and DM, and 25.9 mg x h/L (95% CI, 21.4-40.2) in patients with TB only (P=.003). Similar differences were found for the maximum concentration of rifampicin. No significant differences in time to maximum concentration of rifampicin were observed. The AUC(0-6 h) of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only (geometric mean, 0.60 vs. 3.2 mg x h/L; P=.001). Linear regression analysis revealed that higher body weight (P<.001), the presence of DM (P=.06), and plasma glucose concentration (P=.016) were correlated with exposure to rifampicin.. Exposure (AUC(0-6 h)) to rifampicin was 53% lower in Indonesian patients with TB and DM, compared with patients with TB only. Patients with TB and DM who have a higher body weight may need a higher dose of rifampicin.

Topics: Adult; Antitubercular Agents; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Mycobacterium tuberculosis; Rifampin; Tuberculosis

Intensive chemotherapy for first detected pulmonary tuberculosis was initiated in 110 patients with diabetes mellitus (DM). Types 1 and 2 DM was present in 52 and 58 patients, respectively. In accordance with the WHO recommendations, isoniazid, rifampicin, pyrazinamide, and streptomycin or ethambutol were given to the patients at the first loading stage. Following 2-3 months, they were treated with isoniazid and rifampicin (as well as with pyrazinamide in some cases). A good or fair tolerability of the first stage of chemotherapy was noted in 86 (78.2%) patients with concurrent pathology (Group 1). The signs of intolerability developed in the remaining 24 (21.8%) patients forced them have an individually chosen chemotherapy regime instead of the standard one (Group 2). Both groups were comparable by age, gender, the pattern of a pulmonary process, the types and severity of DM. The effect of treatment was much higher in Group 1 patients. According to the data of bacterioscopy and inoculation, bacterial isolation ceased in them earlier and achieved more frequently than in Group 2 patients (83.7 and 54.5%, respectively; p < 0.05). Better X-ray lung changes were revealed after 4-month therapy. Decay cavity closure after 10 months of treatment was achieved in 69.3 and 30% of the patients in Groups 1 and 2, respectively (p < 0.05). Thus, most patients with DM tolerated intensive chemotherapy for pulmonary tuberculosis well or satisfactorily. The higher efficiency of this therapy than that of individually selected regiment allows the author recommend its wider use in patients with this concomitant pathology.

Topics: Antibiotics, Antitubercular; Antitubercular Agents; Data Interpretation, Statistical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Pyrazinamide; Radiography, Thoracic; Rifampin; Time Factors; Tuberculosis, Pulmonary

Topics: Animals; Animals, Domestic; Anti-Bacterial Agents; Antibiotics, Antitubercular; Diabetes Mellitus, Type 2; Drug Resistance, Bacterial; Fishes; Hand Dermatoses; Humans; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Rifampin; Risk Factors; Skin Diseases, Bacterial; Spinocerebellar Degenerations; Water Microbiology

Topics: Aged; Antibiotics, Antitubercular; Clarithromycin; Diabetes Mellitus, Type 2; Drug Interactions; Drug Therapy, Combination; Ethambutol; Gliclazide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Isoniazid; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin