Safety Of Rifampicin Research Articles

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial.

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.

Clinical Pharmacology of Antituberculosis Drugs in Infants and Children

The antituberculosis drugs used in paediatric patients are: rifampicin, isoniazid, and pyrazinamide. The treatment of infections with rifampicin, isoniazid, and pyrazinamide has been reviewed. The efficacy and safety of rifampicin have been reported in children. The pharmacokinetics of rifampicin have been studied in infants and rifampicin median elimination half-life is 7.1 hours in infants with a postnatal age < 14 days and 3.5 hours in infants with a postnatal age ≥ 14 days. The treatment of children with rifampicin has been described. Rifampicin penetrates into the cerebrospinal fluid and treats the tuberculous meningitis and tuberculous meningo-encephalitis. Rifampicin is poorly transferred across the human placenta and poorly migrates into the breast-milk. The pharmacokinetics of isoniazid have been studied in children and the median elimination half-life of isoniazid is 3.22 hours. The treatment of children with isoniazid has been described and isoniazid poorly migrates into the breast-milk. The pharmacokinetics of pyrazinamide have been studied in children and the median elimination half-life of pyrazinamide is 3.47 hours and pyrazinamide poorly migrates into the breast-milk. The aim of this study is to review the treatment with rifampicin, isoniazid, and pyrazinamide. Rifampicin efficacy and safety, pharmacokinetics, treatment, penetration into the cerebrospinal fluid, treatments of meningitis, transfer across the human placenta, and migration into the breast milk have been reviewed. The efficacy and safety of isoniazid, the pharmacokinetics of isoniazid, and the migration of isoniazid into the breast-milk have been reviewed. The pharmacokinetics of pyrazinamide and the migration of pyrazinamide into the breast-milk have been reviewed.

Adjunctive rifampin therapy for diabetic foot osteomyelitis: A protocol for systematic review and meta-analysis.

The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis. English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3. This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals. This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.

Rifampicin treatment of canine pyoderma due to multidrug-resistant meticillin-resistant staphylococci: a retrospective study of 32 cases.

Rifampicin has received increased interest in veterinary dermatology because of its activity against multidrug-resistant meticillin-resistant staphylococci (MRS). There is limited knowledge about the efficacy and safety of rifampicin in dogs. To provide information on response to treatment and adverse effects in dogs treated with rifampicin for multidrug-resistant MRS pyoderma. Thirty two dogs treated with rifampicin for rifampicin-susceptible multidrug-resistant MRS pyoderma. Retrospective review of medical records, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum activity levels and total bilirubin concentrations, obtained before and throughout the treatment, was performed. Oral rifampicin as sole systemic antimicrobial therapy (median dose 5 mg/kg twice daily) was effective in 71.88% of cases. Topical antimicrobials were used in most cases. Median duration of rifampicin treatment was five weeks for superficial pyoderma and four weeks for deep pyoderma. Gastrointestinal signs were reported in 15% of treated dogs. Statistically significant increases of ALT (P = 0.045) and ALP (P = 0.0002) values after 3-4 weeks of treatment was observed. The median increase was equal to 0.3 and ×1.5 the upper limit of the reference ranges for ALT and ALP, respectively. Oral rifampicin combined with topical antimicrobials can be considered an effective therapeutic option for canine superficial and deep pyoderma caused by rifampicin-susceptible multidrug-resistant MRS. Liver enzyme induction might be the most important cause of ALT and ALP increase associated with rifampicin therapy in dogs.

Rifampicin as Adjunct to Colistin Therapy in the Treatment of Multidrug-Resistant Acinetobacter baumannii

To evaluate the available evidence regarding the efficacy and safety of rifampicin, as adjunct to colistin, in the treatment of multidrug resistant Acinetobacter baumannii (MDR-AB). We searched MEDLINE (1966 to January 2014) using the following search terms: A baumannii, drug resistance, treatment, colistin, and rifampicin and combinations. In addition, the bibliographies of relevant articles were searched for additional citations. The search was limited to English-language references and adults. Studies in which colistin was not administered intravenously were excluded. In addition, we excluded meeting abstracts and single case reports. The search strategy identified 5 observational studies and 2 randomized controlled trials that evaluated the combination of intravenous colistin and rifampicin for the treatment of MDR-AB. All observational studies included a small sample size, and the microbiological clearance associated with the combination therapy ranged from 60% to 100%. The randomized controlled trials reported reduced time to microbiological clearance and higher microbiological eradication rate in the colistin/rifampicin group compared with colistin alone. However, there was no difference between both groups in the overall mortality, infection-related mortality, and the length of stay. Furthermore, rifampicin was associated with a higher incidence of hepatotoxicity. Studies evaluating the combination of rifampicin and colistin in the treatment of MDR-AB are limited. The currently available evidence does not support the addition of rifampicin to colistin because of the lack of improved clinical outcomes with the combination therapy and the risk of rifampicin-induced hepatotoxicity.