Active clinical trials for "Gram-Negative Bacterial Infections"

The primary objectives of this study are to assess the safety, tolerability, and pharmacokinetics (PK) of cefiderocol after single-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections and after multiple-dose administration in hospitalized pediatric participants 3 months to < 18 years of age with suspected or confirmed complicated urinary tract infection (cUTI), hospital-acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP).

The primary purpose of this study is to evaluate the safety and tolerability of imipenem/cilastatin/relebactam (IMI/REL) in participants from birth to less than 18 years of age with confirmed or suspected gram-negative bacterial infection. Participants are expected to require hospitalization through completion of intravenous (IV) study intervention, and have at least one of the following primary infection types: hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI). Participants will be randomized in a 3:1 ratio to receive IMI/REL or active control. This study will also evaluate the efficacy of IMI/REL by assessing all-cause mortality at Day 28 post-randomization, as well as clinical and microbiological response to treatment. It will also evaluate the pharmacokinetics of IMI/REL.

Sepsis is the leading cause of death in intensive care units and a major public health concern in the world. Heparin, a widely used anticoagulant medicine to prevent or treat thrombotic disorders, has been demonstrated to prevent organ damage and lethality in experimental sepsis models. However, the efficacy of heparin in the treatment of clinical sepsis is not consistent. Caspase-11, a cytosolic receptor of LPS, triggers lethal immune responses in sepsis. Recently, we have revealed that heparin prevents cytosolic delivery of LPS and caspase-11 activation in sepsis through inhibiting the heparanase-mediated glycocalyx degradation and the HMGB1- LPS interaction, which is independent of its anticoagulant properties. In our study, it is found that heparin treatment could prevent lethal responses in endotoxemia or Gram-negative sepsis, while caspase-11 deficiency or heparin treatment failed to confer protection against sepsis caused by Staphylococcus aureus, a type of Gram-positive bacterium. It is probably that other pathogens such as Gram-positive bacteria might cause death through mechanisms distinct from that of Gram-negative bacteria. Peptidoglycan, a cell-wall component of Gram-positive bacteria, can cause DIC and impair survival in primates by activating both extrinsic and intrinsic coagulation pathways, which might not be targeted by heparin. We speculate that the discrepancy between the previous clinical trials of heparin might be due to the difference in infected pathogens. Thus, stratification of patients based on the type of invading pathogens might improve the therapeutic efficiency of heparin in sepsis, and this merits future investigations.

The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants. The study is seeking participants who are: 9 months to less than 18 years of age Hospitalized Suspected/known to have a gram-negative infection Receiving intravenous (iv, given directly into a vein) antibiotics Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs. Participants will receive either ATM-AVI or best available therapy (BAT). Both therapies will be given through a vein. Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion. The iv dose of ATM-AVI will be based on the participant's weight and kidney function. The study doctor will determine the iv dose of BAT. During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities. Starting on day 4, the study doctor will decide if participants may be switched to oral therapy. Participants will receive a maximum of 14 days of ATM-AVI treatment. After discharge from the hospital, 1 study visit may be required. Depending on the participant's response, the study duration will be from 33 to 50 days. The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.

Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. These bacteria are of special concern because few therapeutic options are available. Traditionally, the duration of treatment for severe multidrug-resistant (MDR)-GNB infections is 14 days. Studies of severe infections by GNB, regardless of susceptibility profile, have shown that shorter antimicrobial treatments are not inferior to traditional durations of therapy and are associated with a lower incidence of adverse effects. However, there are currently no studies assessing whether shorter duration of antimicrobial treatment is effective for MDR-GNB. This open-label, randomized clinical trial aims to assess the non-inferiority of 7-day antibiotic therapy compared to conventional 14-day treatment in severe infections by MDR-GNB.

The primary purpose of this study is to understand the pharmacokinetics (PK) of single and multiple doses of cefiderocol in children from birth to less than 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections.

Sepsis sometimes occurs in people who have a serious infection. It is caused by toxic substances (toxins) from bacteria and other germs entering your bloodstream. Most people with sepsis will recover with routine medical care before the illness gets more serious. However, in some people, sepsis does become more serious. This severe sepsis can cause damage to internal organs (such as your heart, lungs, kidneys, and liver) and can be life threatening. Special natural fats, (called 'lipoproteins') in our blood are thought to help protect us from the toxins produced by bacteria during sepsis. Levels of these lipoproteins are often low in people with sepsis and this may make it more difficult to recover from the disease. GR270773 is a new drug that has been developed to help the lipoproteins in protecting the body against toxins. GR270773 is made from purified fats and oils from the soyabean and does not contain cholesterol. This research study will test the safety (side effects) of GR270773 and whether or not it is effective in preventing complications in people with severe sepsis.

Antimicrobial resistance is a global health emergency estimated to be responsible for 700,000 deaths per year worldwide, and it is well known that previous antibiotic exposure is the single most contributing factor. For example, the use of non-antipseudomonal agents can increase risk for any P. aeruginosa strain; however, the use of an agent with antipseudomonal activity would select for resistance to that particular antimicrobial agent or class. Demonstrated that each additional day of exposure to any antipseudomonal beta-lactam is associated with an increased risk of new resistance development. The study seeks to determine whether the choice of empiric therapy (i.e., the same agent versus a different agent from prior antibiotic exposure) has any effect on the likelihood of in vitro activity against GN pathogens (GNPs) in a subsequent infection.

This research is important because it allows for the determination of resistance rates to antibiotics that may not be frequently tested by the clinical microbiology laboratory at University of Pittsburgh Medical Center (UPMC)-Presbyterian. It also will provide antibiotic minimum inhibitory concentrations (MICs) for these pathogens which may help in identifying the best empiric antibiotic option for gram-negative blood stream infections based on known pharmacodynamic parameters.

The purpose of this study was to assess the pharmacokinetics, safety, and tolerability of a single intravenous dose of ceftolozane/tazobactam (MK-7625A) in pediatric participants. In each of the 6 age cohorts, an interim analysis of pharmacokinetics (PK) and safety data was conducted after approximately 3 participants had received the initially proposed dose. The interim analysis was to determine whether the initial dose was appropriate based on pre-defined criteria. If data from the interim analysis demonstrated that the initially proposed dose met the above criteria, enrollment was to continue with the same dose administered to approximately 3 additional participants of the same age range. However, if the interim analysis demonstrated that a new optimized dose was required, the new dose was to be administered to approximately 3 additional participants of the same age range.