Clinical Research Directory

Safety of Combined Intravenous Antibiotic and Bacteriophage Therapy in Adults With Cystic Fibrosis and Antibiotic-Resistant Lung Infections

This is a Phase 1, open-label, multi-center pilot study evaluating the safety and microbiological activity of intravenous (IV) bacteriophage therapy in combination with standard IV antibiotics in adults with cystic fibrosis (CF) experiencing pulmonary exacerbations due to antibiotic-resistant bacterial infections. Eligible participants will receive a 7-day course of IV antibiotics, selected by their treating clinician, along with a phage cocktail specifically formulated to target their identified bacterial pathogen (Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans). The primary objective is to assess the safety and tolerability of this combined treatment approach. Secondary and exploratory outcomes include assessment of changes in sputum bacterial burden, lung function (spirometry and oscillometry), quality of life, and bacteriophage pharmacokinetics. Results from this study will inform the feasibility and design of future clinical trials using phage therapy in the CF population.

Immune Resolution After Staphylococcus Aureus Bacteremia

The purpose of this study is to determine how monocyte HLA-DR and other markers of immune function change with time in patients with and without prior immune dysfunction who survive sepsis from Staphylococcus aureus bacteremia. We hypothesize that patients with prior immune dysfunction will have greater reductions in HLA-DR and other markers of immune function after an episode of sepsis than people who do not have prior immune dysfunction.

Pharmacology of Mupirocin in Nasal Application in Healthy Volunteers: Monocentric Study

Mupirocin is an old antibiotic used topically since the 1970s. Initially used in the treatment of skin infections for its antistaphylococcal action, it is now part of the decolonization strategy for Staphylococcus aureus (SA) carriage, in association with chlorhexidine. This decolonization strategy has been recommended in France for preoperative cardiac surgery in nasal SA carriers since 2013 by the French Hospital Hygiene Society, and recommended for cardiac and orthopedic surgery in SA carriers by the World Health Organization (WHO) since 2016. This strategy includes nasal decolonization using mupirocin ointment nasally (2 to 3 applications/day), a daily shower with chlorhexidine soap and + /- mouthwashes all over 5 days, often pre-operatively. As a result, mupirocin is now widely used throughout the world, all the more so as, for reasons of ease of organization, many centers use this decolonization procedure universally (i.e. without prior screening for Staphylococcus aureus carriage), thus further increasing the use of this molecule. Mupirocin administration methods are very vague, ranging from 2 to 3 applications per day and the application of "a match head", i.e. 50 mg, to 500 mg per nostril. Mupirocin is bacteriostatic at low doses, becoming bactericidal at higher concentrations; low concentrations could favor the selection of resistance, so using the most effective dosage seems essential. This lack of precision in administration is linked to an almost complete ignorance of the pharmacokinetics of mupirocin and its metabolite (monic acid) after nasal application. It therefore seems essential to conduct a pharmacokinetic study of this molecule, in order to eventually offer patients the regimen with the administration methods offering the best characteristics in terms of dosage and efficacy.

Bacteriophage Therapy for Methicillin-Sensitive Staphylococcus Aureus Prosthetic Joint Infection

This is a single-patient, phase I/II clinical trial that aims to evaluate the potential of a bacteriophage cocktail to treat and prevent the recurrence of a methicillin-susceptible Staphylococcus aureus prosthetic joint infection of the hip. The patient has exhausted all conventional therapies, both surgical and medical, at considerable detriment to his quality of life. The treatment involves a one time, intra-operative injection of bacteriophages into the joint and 14 days of intravenous phage therapy. The goal is to eliminate the infection and prevent further complications, providing a potential new treatment avenue for patients with difficult-to-treat infections.

Dalbavancin Versus Standard Antibiotic Therapy for Catheter-related Bloodstream Infections Due to Staphylococcus Aureus

The primary objective of the study is to demonstrate, among patients with non-complicated CR-BSIs due to S. aureus, that a single-dose of intravenous (IV) dalbavancin 1500 mg is non-inferior to standard documented antibiotic therapy for 14 days according to national guidelines at DAY 30 (Long follow up visit). As the secondary objectives, the study aims to evaluate according to treatment group: 1. Cure rate at DAY 14 and DAY 90 (EOS); 2. Mortality rate within 90 days of follow-up; 3. Time to negativation of blood cultures; 4. Patient's quality of life; 5. Hospitalization length of stay; 6. Cost-utility analyses; 7. Occurrence of any adverse event (AE and SAE), until Day 90 (EOS).

Adjunctive Clindamycin for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled Trial

This is an exploratory study to evaluate the effect of adjunctive clindamycin in the treatment of skin and soft-tissue infections due to Staphylococcus aureus in patients from Sierra Leone. The study hypothesizes that clindamycin, when added to routine treatment, will lead to a more rapid clinical resolution and less frequent recurrences of infection.

Plasma Pharmacological Monitoring of M Penicillins in Methicillin-sensitive Staphylococcus Aureus Bacteremia

The treatment of Methicillin-sensitive Staphylococcus aureus bacteremia is based on the first-line use of cefazolin or M penicillins (oxacillin and cloxacillin). The use of the latter is recommended at high doses (150-200 mg/kg/24h). In a study on infectious endocarditis, 52 of 56 patients with staphylococcal endocarditis treated with (cl)oxacillin were overdosed with the recommended doses. Although the main mechanism of renal toxicity described for M penicillins is immunoallergic, a frequent overdose is observed in cases of acute renal failure with M penicillins. There is also a significant association between overdose and risk of neurological toxicity. The currently recommended treatment duration is a minimum of 14 days of IV treatment from the first negative blood culture, which leaves room for carrying out a plasma assay and possible dosage adjustment subsequently. Overdose is a risk factor for nephrotoxicity and neurotoxicity. Plasma level could be predictive of clinical success. Systematic plasma dosing would reduce the risk of toxicity and improve the clinical cure rate.

Serum Based Diagnosis of and Monitoring of Infection Recovery in Orthopedic Spine Implant Infections

The goal of this study is to test a new way to diagnose and track treatment of spine infections caused by the bacteria Staphylococcus aureus.

Nasal Decolonization of Dialysis Patients Noses

Hemodialysis patients are at high-risk for infections, specifically Staphylococcus aureus infections. The investigators propose to 1) implement a novel intervention (nasal povidone-iodine at each hemodialysis session) to prevent S. aureus infections using a stepped-wedge cluster randomized trial, and 2) evaluate the feasibility and acceptability of this intervention. If successful, this intervention can be used among hemodialysis patients, and evaluated in other high-risk patient populations to prevent S. aureus infections.

18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia

Having bacteria in the blood can be very dangerous. This is called bacteraemia (or bacteremia) or bloodstream infection. It can lead to problems across the whole body, which is what happens in sepsis. Bacteria called Staphylococcus aureus (S. aureus) cause one kind of bacteraemia. Up to a third of people with this condition die within three months, even with antibiotics. One reason for such severe problems is that the bacteria can spread almost anywhere in the body, and hide in places where they are very hard to find. When people with S. aureus bacteraemia come into hospital and have had antibiotics, doctors sometimes cannot tell if they still have an infection source (called a 'focus') hiding in their body. The focus can be like an abscess and may need removing or the pus draining out. A focus might be obvious, if there is pain or swelling, or it might be hidden and deep. If these 'foci' can be found, then doctors can treat them and this helps to cure patients. To improve survival for patients with these life-threatening infections, it is vital that doctors find the focus of S. aureus bacteraemia as quickly as possible. However, the research team do not know the best way to do this. Most patients with S. aureus bacteraemia have a chest X-ray and a scan of the heart valves. Patients may go to the scanning department lots of times while doctors try to work out where these foci are. This is uncomfortable and takes a lot of time. In about 1 in 5 cases the doctors still cannot find the focus. This is very worrying for patients, their relatives and doctors. This study has been designed by researchers, doctors and patient advocates. It aims to work out if fewer patients may die when a specific type of scan called a 'PET/CT' is done quickly, because it finds more foci. To do this the team plan to do a clinical trial in patients with S. aureus bacteraemia. Half of the patients will receive the usual tests that patients currently get and the other half will receive an extra scan as soon as possible. The patients will be chosen randomly (like the flip of a coin) to go into one of the 2 groups. A year into the trial, an independent committee will check the results to make sure the extra scan is finding more foci. If this is the case, the trial will carry on. At the end of the study, we will share the results globally. The findings are expected to change the way this dangerous condition is managed, so patients do better.