Active clinical trials for "Endocarditis"

Drug resistance of G+ cocci is a severe healthcare problem. According to the Ministry of Health National Antimicrobial Resistant Investigation Net (mohnarin) surveillance report, the isolation rate of MRSA is some 60% in China. MRSA infection has become a serious clinical problem; Vancomycin is a bactericidal glycopeptide antibiotic which inhibits bacterial growth by hindering the synthesis of cell wall in bacteria. It exerts strong antibiotic effect to Gram+ bacteria. It is indicated for serious staphylococcus infections especially MRSA infection and has become the gold standard agent in MRSA treatment; Vancomycin is a time-dependent antibiotic, its clinical and microbiological efficacy is related to area under curve（ AUC）/minimum inhibitory concentration （MIC ）(AUIC). Cmin at steady state is an surrogate parameter of AUIC, which is closely associated to the efficacy; AUIC >400 and Cmin between 15~20 mg/L are recommended for effective vancomycin treatment by Infectious Diseases Society of America （IDSA） although it is still disputable; Due to the absence of PK/PD study on vancomycin in China, administration of vancomycin is performed in reference to the recommendation of IDSA. Its suitability to Chinese patients is still to be clarified; Plasma concentrations of vancomycin vary significantly between population and individuals. Factors such as large-volume fluid infusion, hypoproteinemia and renal clearance, etc. will influence the distribution and excretion of vancomycin, resulting in different plasma concentrations between individuals. Results of PK studies differ greatly between China and abroad. Administration based on the AUIC or Cmin recommended by IDSA would not be suitable to Chinese patients. Given the definite long-term benefit of vancomycin treatment, the AUIC or Cmin suitable to Chinese patients must be identified by clinical study. The PK/PD study on vancomycin in the treatment to MRSA septicemia and endocarditis is of great significance for more reasonable use and improved therapeutic efficacy of MRSA infection.

Infective endocarditis is a microbial infection of the endocardial surface of the heart.

The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. In the other hand, a new treatment schema useful in OPAT programs is proposed, but there is still a lack of pharmacokinetic data to support it. The plasma drug concentrations will be measured in both cases, comparing the minimal drug concentration observed and the pharmacokinetic profiles of the two regimens.

Infectious endocarditis (IE) is defined as an infection anywhere on the endocardium, most often localised to the cardiac valves. It is an infection with an increasing incidence and in Denmark with 6-700 new cases annually. Approximately 45% of the patients must undergo cardiac surgery with replacement of infected cardiac valves by prosthetic valves. Recently, the formation of biofilms infections has drawn attention with respect to the effects of hyperbaric re-oxygenation of stricken tissues as anaerobic bacterial metabolism with low levels of activity within the biofilm environment, may be responsible for the development of antimicrobial resistance. Polymorphonuclear leukocytes (PMNs) consume available oxygen in the conversion of oxygen to ROS and in the formation of reactive nitrogen species (RNS) by inducible nitric oxide (iNOS) as PMN's are activated by bacteria. In pre-clinical context the effect of hyperbaric oxygen treatment (HBOT) in re-oxygenating biofilm related infections have been demonstrated in infected lungs with Pseudomonas aeruginosa and staphylococcus aureus endocarditis. Adjunctive HBOT has never been offered to patients with IE. However, HBOT may be associated with reduced compliance and side effects, such as equalisation problems of ears and sinuses and confinement anxiety, and the treatment is organizational challenging. On this basis the investigators suggest an initial feasibility study as the basis for a later and larger scaled randomized controlled trial of HBOT in patients with IE.

The purpose of the EARLY study is to evaluate the efficacy and effectiveness of early surgery in patients with Infective Endocarditis (IE).

Background: Prognosis of infective endocarditis is poor and has remained steady over the last four decades. Several nonrandomized studies suggest that early surgery could improve prognosis. Methods: The early surgery in infective endocarditis study (ENDOVAL 1) is a multicenter, prospective, randomized study designed to compare the state-of-the-art therapeutic strategy (that advised by the international societies in their guidelines) with the early surgery strategy in high-risk patients with infective endocarditis. Patients with infective endocarditis without indication for surgery will be included if they meet at least one of the following: 1) early-onset prosthetic endocarditis; 2) Staphylococcus aureus endocarditis; 3) periannular complications; 4) new-onset conduction abnormalities; 5) vegetations longer than 10 mm in diameter; 6) new-onset severe valvular disfunction. A total of 216 patients will be randomized to either of the two strategies. Stratification will be done within 3 days of admission. In the early surgery arm, the procedure will be performed within 48 hours of randomization. The only event to be considered will be death within 30 days. The study will be extended to 1 year. In the follow-up substudy, death and a new episode of endocarditis will be regarded as events. Conclusion: The early surgery in infective endocarditis study (ENDOVAL 1), the first randomized in endocarditis, will provide crucial information regarding the putative benefit of early surgery over the state-of-the-art therapeutic approach in high-risk patients with infective endocarditis.

The purpose of this study is to assess the impact of 18-FDG positron emission tomography (PET)/computed tomography (CT) imaging in the management of patients with suspected or proven IE in detecting cardiac valve damages and other extracardiac complications. The study will evaluate whether this procedure can change the clinical decisions (treatments, valve surgery, patients' overall care) and modify the diagnosis of IE.

With aging of the general population and broadening indications, the number of pacemaker recipients is steadily increasing. The incidence of infections of the implanted material, a dreaded major complication, is also rising. The diagnosis is evident in presence of an abscessed pocket, cutaneous breakthrough of the pulse generator or vegetations attached to the lead. On the other hand, a proportion of patients present with less specific clinical manifestations and a pacemaker recipient may be recurrently hospitalized for an infectious disorder of unknown origin despite detailed investigations. Without proof of lead infection, removal of the system without confirmation of its infection is usually proposed, despite the known morbidity and mortality associated with the extraction procedure (0.5 to 2%). Positive culture of the leads implies that the leads were involved in the infectious process. In recent years, 18FDG-PET-CT scan has made promising contributions in different areas including imaging to detect infection at different organ sites. Absence of hyperfixation of the lead, identified by 18FDG-PET/CT scan may be an accurate sign of absence of pacing system infection. The extraction of intracardiac implanted material, when it is indicated by the current standard strategy, may result in negative bacteriological cultures in 10 to 25% of patients, even when they did not receive antibiotics before extraction. The hypothesis of the study is that a new strategy adding 18FDG-PET-CT to the current strategy may avoid or reduce these false-positives. Therefore it is hypothesized that the sensitivity of 18FDG-PET-CT will be high enough to avoid unnecessary extractions of uninfected leads, resulting in a high negative predictive value of the new diagnostic strategy incorporating 18FDG-PET-CT. The present study aims at providing valid estimates of diagnostic accuracy parameters of 18FDG-PET-CT, especially its sensitivity. For this clinical study, firstly, 18FDG-PET-CT exam will be performed in patients, with suspicion of pacing or defibrillation lead infection, hospitalized in cardiology unit; secondarily, an intervention for the extraction of the intra-cardiac material, under general anesthesia, will be practiced and then a bacteriological culture for extracted material will be required. The end of study visit is complete the last day of material extraction. The follow up will last 2 to 7 days.

The primary purpose is to improve and quicken the microbial diagnosis in severe infections, since only one third of the cases are documented by blood cultures and adequate anti-infective therapy in the 48 hours reduced mortality and morbidity. Our hypothesis is that detection of microbial DNA in blood by real time PCR may increase the number of cases diagnosed for bacteraemia or fungemia and shorten the time to positive results, which will provide information for an adequate anti-infectious therapy.

The diagnosis of prosthetic valve endocarditis (PVE) remains challenging. In PVE cases, initial echocardiography is normal or inconclusive in almost 30% of cases, leading to a decreased diagnostic accuracy for the modified Duke criteria. Aims: The investigators sought to determine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for diagnosing PVE. Methods: In two referral French centers (Timone Hospial, Marseille and Georges Pompidou European Hospital, Paris), the investigators plan to include consecutive patients suspected of having PVE. All of the patients will be subjected to clinical, microbiological, and echocardiographic evaluation. Cardiac PET/CT will be performed at admission and the data analysis will be based on visual interpretation and quantitative measurement of FDG uptake (SUVmax). The final diagnosis will be defined according to the clinical and/or pathological modified Duke criteria determined during a 3-month follow-up (gold standard).