Clinical Research Directory

Febrile Infants Swedish Study

Approximately one million febrile infants aged ≤60 days present annually to pediatric emergency departments (PEDs) in Europe and the United States. Although fewer than 5% are diagnosed with meningitis or bacteremia (invasive bacterial infections - IBIs), and 10-15% with urinary tract infections (UTIs), current guidelines recommend extensive diagnostic evaluations, hospitalization, and empirical treatment with broad-spectrum parenteral antibiotics. This approach may contribute to medical overuse, with implications for patient care, healthcare resource utilization, and environmental sustainability. The Febrile Infants Swedish Study (FISS) is a prospective observational study conducted across 11 PEDs in Sweden. All febrile infants aged ≤60 days presenting to participating sites will be eligible. A new clinical guideline for the management of infants with fever without source (FWS) will be implemented in 7 PEDs, while 4 PEDs will continue with current standard practice and serve as a comparison group. The study is expected to run for approximately two years and aims to recruit a minimum of 2,500 febrile infants

Evaluation of Emergency Medicine Pharmacist Impact on Blood Culture Review Following Emergency Department Discharge

Patients are commonly discharged from the Emergency Department(ED) with pending blood culture results. Blood cultures can take up to 48 hours to become positive which is why it is important to notify patients with true positive cultures as soon as possible. Delay in notification can lead to other serious complications such as sepsis, septic shock, and death. The American College of Emergency Physicians states pharmacists serve a critical role in ensuring efficient, safe, and effective medication use in the ED and advocates for health systems to support dedicated roles for pharmacists within the ED. Pharmacists help to decrease the workload on the healthcare team, especially in the ED where there is high volume and acuity.Emergency medicine pharmacist (EMP) play a significant role in the optimization of therapy, medication safety, and reducing costs. There is strong evidence for the positive impact EMPs have on microbiological culture review. Overall, pharmacist review of late cultures results in higher rates of appropriate antimicrobial therapy and decreased missed interventions.These prior studies focused on the review of microbiological tests, including sexually transmitted infections, urine, and wound cultures; however, there was limited data to support the role of pharmacists evaluating late blood culture results.

Structural and Microbiological Characterization of Arterial Catheter Biofilm in ICU's Patients Using Optical Coherence Tomography

29.3% of bacteremias in intensive care units (ICU) are linked to vascular devices, including 7.7% to arterial catheters, with an influence on both morbility and mortality. It is now accepted that biofilm as a role on bacterial development on inner surface of vascular devices but there is yet a lack of clinical relevant data documenting a causal relation between biofilm formation and bacteremias. The investigators assume that a better structural and microbiological characterization of arterial catheter biofilm in ICU patients could help preventing bacteremias or have a more specific treatment when it appears.

Echocardiography Versus no Echocardiography in S. Aureus Bacteraemia and VIRSTA Score < 3

Staphylococcus aureus is the most frequent cause of both healthcare-associated and community-acquired bloodstream infections worldwide. Infective endocarditis (IE) has been detected in 5-17% of cases and is a determinant of poor prognosis. The investigators developed a score (the VIRSTA score) based on patients' characteristics to rule out IE with high confidence (negative predictive value (NPV) above 99%) in patients with SAB. This score, with a cut-off of 3 has been externally validated by two international studies which have also established its high NPV. The 2023 European society of cardiology (ESC) guidelines state that echocardiography should be considered in all patients with Staphylococcus aureus bacteremia (SAB) using risk scores (including VIRSTA score) to guide the use or not of echocardiography. While recommended, the investigators think that VIRSTA score must be evaluated in terms of patients' outcome.

Beta-lactam Plus Levofloxacin to Enhance Therapy in Streptococcal Septicemia

A double-blind randomized controlled trial comparing beta-lactam plus levofloxacin versus beta-lactam monotherapy for the treatment of Streptococcal bacteremia

Bacteremia From Periodontal Treatment to Elucidate the Underpinnings of Sepsis

Approximately 40,000 Swedes suffer from sepsiseach year, about 20% die. Biomarkers that are sensitive to current or previous bacteremia are needed in the treatment of sepsis. Bacteremia from periodontal treatment is predictive and occurs in 13-75%. Cardiovascular disease (CVD) is the number one cause of death in industrialized countries and the impact of bacteria and their products need to be elucidated. The study's hypothesis is to utilize bacteremia from periodontal treatment to evaluate biological markers for current or previous bacteremia. A. What are the long term clinical, and 'omics related CVD-phenotypical effects from treating periodontal disease compared to an untreated group? B. Can biomarkers be used for detecting a bacteremia or previous bacteremia? C. Are the effects from bacteremia on cardiovascular biomarkers related to the individual's antimicrobial peptide profile? D. Does the presence of bacterial proteases, such as gingipain, relate to having a bacteremia from periodontal treatment and the systemic response from a bacteremia? Significance: The project has the potential to shorten the time to treat sepsis, which in turn shortens hospital stay and higher survival. The possible definition of protective AMP-profile could translate to future pharmacologic intervention and improve the treatment of sepsis as well as prophylactic treatment at dental treatments. An elucidation of the impact of bacteria and their products on CVD could lead to personalized medicine targeting anti-inflammation and anti-oxidative stress in subjects with periodontitis. As of March 2024 78 subjects have been included and we anticipate to keep the time-line that we set up.

Improving Therapeutic Drug Monitoring and Dosing for Vancomycin in Young Infants With Infections (VANCAPP) (Part 2)

A challenge to intermittent vancomycin dosing in young infants is the avoidable delay caused by the need to wait until steady state (i.e. when the drug concentrations are in equilibrium) to measure a vancomycin concentration, as this generally occurs 24 to 48 hours after starting treatment. If the target concentration is not achieved, the dose needs to be adjusted, resulting in further delays in an infant achieving the concentration required to treat their infection. The purpose of this study is to assess the use of early therapeutic drug monitoring (first-dose trough) and, if needed, early dose adjustment, in achieving target vancomycin concentrations at steady state. A dose adjustment calculator (available through a web application) will be used to determine the need for dose adjustment (based on predicted steady state concentration) and recommend an adjusted dose if required.

Impact of Blood Cultures Drawn From Arterial Lines on the Incidence of Contamination, Detection of Bacteremia, and Blood Culture Volume

Taking blood cultures is an important and very common procedure in intensive care units due to the high incidence of sepsis and the need for rapid and accurate identification of bacteremia. However, despite the importance of taking a sufficient volume of blood for the purpose of identifying bacterial growth in the blood, the average blood volume in blood cultures at our institution ranges from 3.5-4 ml per bottle (where the desired volume is 10 ml). Taking an insufficient amount of blood reduces the ability of the bacteriological laboratory to detect bacterial growth and thus may lead to a delay or missed diagnosis of bacteremia, identification of the pathogen, and adjustment of appropriate treatment according to sensitivities. In intensive care units, most patients are monitored using an arterial catheter, which allows for frequent blood tests without the need to puncture the patient. Following recently published studies that showed that there is no significant difference in the incidence of contamination when taking blood cultures from an arterial catheter compared to a peripheral vein puncture, and in order to improve our ability to identify bacteremia, it was decided to implement a new protocol in the General Intensive Care Unit that includes taking blood cultures from an arterial catheter. According to the new protocol, it was decided that when taking blood cultures from a patient with an arterial catheter, one pair of cultures should be taken from the arterial catheter and another pair from a peripheral vein puncture. In this study, we would like to examine the contamination rate of blood cultures, the identification of true bacteremia, and the collection of appropriate blood volume and number of blood specimens taken in patients hospitalized in the General Intensive Care Unit at our institution, while analyzing differences between the period before the implementation of the new protocol and the period after the implementation, and differences between cultures taken from an arterial catheter and from a peripheral vein puncture.

Reducing Risk for Infective Endocarditis

This clinical trial is studying if bacteria found in a participant's bloodstream after brushing their teeth can be prevented with a dental cleaning and more education on how to best brush and care for their teeth. One group of participants will have a dental cleaning and oral health instructions and the other group of participants will not. Researchers will compare the blood test results from the two groups to see if the education made a difference in preventing bacteria and how long it stays in the bloodstream.

Prospective Validation of GRADY: A Machine Learning Model for Early Sepsis and Bacteremia Detection in ICU Patients

This study aims to prospectively validate the GRADY prediction models, which use machine learning algorithms to estimate the risk of gram-negative bacteremia and sepsis in intensive care unit (ICU) patients based on routinely collected vital signs and laboratory data. Sepsis, a life-threatening condition associated with high ICU mortality, requires early diagnosis and treatment-yet current diagnostic methods relying on blood cultures are time-consuming. Existing scoring systems such as SOFA, SIRS, and NEWS2 often lack sufficient sensitivity and specificity in early sepsis detection. Unlike traditional tools, the GRADY models seek to provide earlier and more accurate risk stratification. This study will compare the clinical performance of GRADY models against standard scoring systems and explore their integration as early warning tools to support rapid intervention and improve outcomes in critical care.

PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae blood-stream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.

Epidemiology of Antimicrobial-use and Antimicrobial-resistant Infections in Four Hospitals in Thailand

The main goal of this retrospective observational study is to understand how stepping down antibiotic treatment (called antibiotic de-escalation) affects patients who receive it compared to those who don't after received a short-course (≤7 days) of parenteral antibiotics. The investigators will use past medical records from four public referral hospitals in Thailand from the year 2019 to 2024. The investigators will firstly evaluate which types of patients are more likely to receive antibiotic de-escalation. Then, the investigators will estimate the impact of antibiotic de-escalation, while taking those differences into account. This way, it will help us understand the impact of antibiotic de-escalation in real-world clinical practice. The investigators also aim to assess how accurate automated outbreak detection systems are at detecting outbreaks, evaluate patterns of antimicrobial use and antimicrobial-resistant infections, and develop new indicators for antimicrobial stewardship that are applicable for local and national actions in low and middle-income countries.

Monocyte Distribution Width (MDW) in the General Population of Emergency Department Patients With and Without Bacteremia

This project will evaluate the usefulness of Monocyte Distribution Width (MDW) for the diagnosis of blood culture positivity (BSI) in patients in the Emergency Department (ED) and reevaluate the usefulness of MDW in patients with BSI and sepsis. Consequently, if MDW indicate a high likelihood of bacteremia antibiotic management in patients with suspected bacterial infections will be changed and aid appropriate antibiotic administration.

Outcomes of Empiric Antibiotic Therapy Based on Hospital Antibiograms in Organ Transplant Recipients with Bacteraemia

The purpose of this observational study is to examine how using the hospital cumulative antibiogram to guide empirical antibiotic therapy affects outcomes in patients with bloodstream infections who have undergone solid organ transplants. The key question is: does the use of a hospital cumulative antibiogram reduce mortality and improve outcomes in these patients?

Surveillance of AMR in DRC

This study addresses knowledge gaps regarding antimicrobial resistance (AMR) in sub-Saharan Africa, focusing on evaluating the feasibility of AMR surveillance and enhancing local research capacity. Conducted at a general referral hospital in semirural Kinshasa, DRC, the study will investigate bacterial infections, their resistance profiles, and related risk factors, including co-infections such as malaria.

Fosfomycin I.v. for Treatment of Severely Infected Patients

The purpose of this European, multicentric, prospective, non-interventional study is to document and evaluate the efficacy and safety of the treatment of severely infected patients with intravenously administered fosfomycin, including patients with osteomyelitis, complicated urinary tract infection, nosocomial lower respiratory tract infection, bacterial meningitis/central nervous system infection, bacteraemia/sepsis, skin and soft tissue infection, endocarditis or other infections, each as far as covered by the respective nationally relevant SmPC.

Impact of Performing a Rapid Antibiotic Susceptibility Test on Antibiotic Therapy Adaptation in Adult Patients with Enterobacterales Bacteremia

Bacteremia is defined as the presence of bacteria in the blood. They can potentially lead to life-threatening septic shock. Effective probabilistic antibiotic therapy must therefore be initiated immediately after blood cultures have been taken. To diagnose bacteremia, blood culture bottles must first be incubated, which allows bacterial growth and early detection. Then, as soon as the sample is positive, an antibiogram of the incriminated bacterium is carried out by inoculation on MH (Mueller Hinton) medium. This diffusion antibiogram is the reference method and is obtained 24 hours after the vial is positive, i.e. around 48 hours after blood cultures are taken. American recommendations agree that it is crucial to use rapid diagnostic tests to obtain the antibiogram. Antibiotic susceptibility test data can be used to broaden the spectrum of antibiotics in the event of ineffective therapy. They can also be used to reduce the spectrum of broad-spectrum antibiotics. This is part of the proper use of antibiotics and the reduction of multi-resistant bacteria (MRB) or highly resistant bacteria (HRB). Finally, it is also possible to carry out an early oral relay, thus avoiding intravenous infusions and their complications, and potentially reducing hospitalization times. The investigators have evaluated a rapid antibiogram by diffusion on MHR-SIR (Mueller-Hinton Rapid-SIR) medium from the blood culture bottle. The investigators were able to obtain antibiogram results 7 hours after blood culture positivity, with excellent correlation compared with the standard method after 24 hours incubation on MH (Mueller-Hinton). The antibiotics tested were the same as with the standard method. Secondly, The investigators were able to evaluate prospectively the impact of diffusion antibiotic susceptibility testing on MHR-SIR medium on early modification of antibiotic therapy in bacteremia, on 167 patients Antibiotic susceptibility test data on MHR-SIR enabled us to adapt antibiotic therapy 8 hours after blood culture positivity for 74 patients (44%). Antibiotic therapy was ineffective for 30 patients (18%) and was therefore extended. It also enabled us to reduce the spectrum of antibiotic therapy, in particular through early oral relay, for 44 patients (26%). The aim of this multicenter trial is to validate on a large scale this strategy for obtaining rapid antibiotic susceptibility test results, with significant consequences in terms of optimizing antibiotic therapy.

Knowledge Attitude and Practice Regarding Bloodstream Bacterial Infections and Antibiotics Usage Among Doctors.

This study is designed to use a questionnaire to assess doctors' knowledge, attitudes, and practices regarding bloodstream bacterial infections and antibiotic use in Tawam and Al Ain tertiary Hospitals (both hospitals have the same medical team) in Al Ain City, UAE.

An Oral Doxycycline Regimen to Prevent Bacteremia Following Dental Procedures

Although controversy exists regarding the efficacy of antibiotic prophylaxis for patients at risk of infective endocarditis, expert committees continue to publish recommendations for antibiotic prophylactic regimens. The last American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines include several important changes, highlighting that clindamycin (CLI) is no longer recommended as an alternative to amoxicillin in those allergic to penicillin. This new project aims to evaluate the effectiveness of oral doxycycline in preventing post-dental extraction bloodstream infection.

Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs

To evaluate if the combination of pivmecillinam and clavulanic acid (PAC) is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in patients with febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).

Lebanese Interhospital Pneumococcal Surveillance Program

Streptococcus pneumoniae (pneumococcus) is a bacterium that causes severe infections in children and adults such as meningitis, pneumonia, and blood stream infection. There are many types of these bacteria defined by the type of sugar coat that they have. These are classified as serotypes. There are common serotypes that cause severe disease and are preventable by vaccination of children. Other less common types are more difficult to prevent. The investigators aim to determine the serotypes that cause invasive pneumococcal disease in Lebanon and to study their sensitivity to different antibiotics. The investigators will collect bacterial isolates from different hospitals in Lebanon isolated from the blood or spinal fluid of patients with invasive pneumococcal disease. This information will help the investigators determine the usefulness of available pneumococcal vaccines in preventing these infections. The data will be distributed to all primary care physicians treating children in Lebanon and will be shared with the Ministry of Health.