Clinical Research Directory

Risk Factors for Colonization or Infection With Carbapenem-Resistant Enterobacteriaceae in Children

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly identified in children in China. Pediatric intensive care unit (PICU) is the high-risk area. However, data on the epidemiology of CRE in hospitalized children in PICU are limited. The objectives of this study are to characterize the risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. The investigators will perform a single retrospective study from January 2018 to December 2019 at PICU of Children's Hospital of Fudan University .

Microbiological and Clinical Characteristics of Severe Infections Caused by Carbapenem-Resistant Enterobacterales

Severe infections caused by carbapenem-resistant Enterobacterales (CRE) represent a challenge for the clinicians, considering the high mortality rate of these infections. Data regarding the prevalence of CRE, clonal analysis, resistant genes (resistome) and virulence genes (virulome) molecular analyses, and clinical outcomes of infected patients are scarce. Thus, creating a network to Standardize and implement microbiological sourveillance could be crucial to answer this challenge. Our group consisting of the, UOC of Infectious Diseases and UOC of Microbiology (Prof Sanguinetti), the Microbiology Unit of the University of Catania (Prof. Stefania Stefani), the local Infectious Disease Unit (Dr Carmelo Iacobello) the Microbiology Unit of the "Magna Graecia'' University (Prof. Giovanni Matera) and the UOC of Infectious and Tropical Diseases UMG Catanzaro Prof Enrico Maria Trecarichi, has already started a project with promising ad interim results on this topic.

Different Methods of Aerosolized Polymyxin B Inhalation for Treating Carbapenem-Resistant Gram-Negative Bacterial Pneumonia.

Study Design: A randomized, open-label, parallel-group clinical trial comparing the efficacy and safety of jet nebulization versus vibrating mesh nebulization of sulfate polymyxin B in mechanically ventilated patients with carbapenem-resistant Gram-negative bacterial pneumonia. Participants: 144 patients (72 per group) will be enrolled from December 2023 to December 2025. Interventions: Group A: 25mg polymyxin B + 5ml sterile water via jet nebulizer (respirator-assisted). Group B: 25mg polymyxin B + 5ml sterile water via vibrating mesh nebulizer (respirator-assisted). Both groups receive additional intravenous polymyxin B (2.0mg/kg loading dose, followed by 1.25mg/kg every 12h) starting 12h after nebulization. Treatment duration: 14 days. Key Procedures: Nebulization parameters: Fixed ventilator settings (SIMV+PSV mode, tidal volume 8ml/kg, PEEP 6cmH₂O). Bronchoalveolar lavage (BAL) and blood sampling: BAL fluid (BALF) and blood collected pre-nebulization (baseline), 1h post-nebulization, and at steady-state (days 3-7). BALF analyzed for polymyxin B concentration, urea nitrogen, and inflammatory mediators (IL-6, TNF-α, etc.). Primary Outcomes: Clinical efficacy: Total response rate (cure + improvement). 28-day survival rate. Time to fever resolution and bacterial clearance. Drug exposure: Polymyxin B concentration in alveolar epithelial lining fluid (ELF) and blood. Secondary Outcomes: Inflammatory response: Changes in BALF and serum IL-6, TNF-α, CRP levels. Safety: Nephrotoxicity (changes in serum creatinine/urea nitrogen). Airway complications (bronchospasm incidence). Assessment Timeline: Clinical monitoring: Daily evaluation of vital signs, sputum volume, and ventilator parameters. Lab tests: Blood tests (hematology, renal function, inflammatory markers) at baseline, days 3/7/14. Microbiological evaluation: Sputum cultures on days 3/7/14. Statistical Analysis: Efficacy and safety endpoints compared between groups using t-tests or chi-square tests. A p-value \<0.05 will be considered statistically significant.

Interventions to Decrease CRE Colonization and Transmission Between Hospitals, Households, Communities and Domesticated Animals

Carbapenem resistant Enterobacteriaceae (CRE) colonization of patients discharged from hospitals is a source of transmission to the community. In a cluster randomized controlled trial the effect of a bundle of interventions will be assessed on CRE transmission from CRE+ index patient discharged from hospital to HouseHold (HH) members. The districts in two provinces will be randomized to intervention or control. An information, communication, education and hygiene intervention, developed in collaboration with local health authorities, will aim to improve hygiene and decrease antibiotic (AB) use. The effect will be evaluated on CRE transmission between HH members, livestock and environment through consecutive CRE screening using fecal and hospital effluent samples cultured on carbapenem selective media. Knowledge, Attitudes, Practice surveys with smartphones will assess health seeking, AB use and hygiene adherence, hence detecting the effect of interventions. If transmission of CRE +/- Colistin Resistant Enterobacteriaceae (CoRE, common among livestocks) is detected the source will be investigated including livestock and food, targeted information will be given and evaluated. In hospitals the effect of cohort care will be assessed on CRE acquisition, hospital acquired infection, treatment outcome, costeffectiveness and contamination in sewage water. Mechanisms of resistance, relatedness of CRE isolates in different One Health departments, and rate of CRE transmission from humans to animals and vice versa, will be assessed through Whole Genome Sequencing (WGS).

Efficacy and Safety of Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection

Colistin can be used to treat the infection caused by carbapenem-resistant enterobacteriaceae(CRE). In China, patients diagnosed with Hospital-acquired-pneumonia (HAP)or bloodstream infection caused by CRE are recruited, and randomly assigned to two groups, and in one group the patients accept treatment with colistin, however in another group, the patients accept treatment without colistin. The efficacy and safety of the treatment between the two groups are compared.

Safety and Efficacy of Fecal Microbiota Transplantation

The gut microbiota is critical to health and functions with a level of complexity comparable to that of an organ system. Dysbiosis, or alterations of this gut microbiota ecology, have been implicated in a number of disease states. Fecal microbiota transplantation (FMT), defined as infusion of feces from healthy donors to affected subjects, is a method to restore a balanced gut microbiota and has attracted great interest in recent years due to its efficacy and ease of use. FMT is now recommended as the most effective therapy for CDI not responding to standard therapies. Recent studies have suggested that dysbiosis is associated with a variety of disorders, and that FMT could be a useful treatment. Randomized controlled trial has been conducted in a number of disorders and shown positive results, including alcoholic hepatitis, Crohn's disease (CD), ulcerative colitis (UC), pouchitis, irritable bowel syndrome (IBS), hepatic encephalopathy and metabolic syndrome. Case series/reports and pilot studies has shown positive results in other disorders including Celiac disease, functional dyspepsia, constipation, metabolic syndrome such as diabetes mellitus, multidrug-resistant, hepatic encephalopathy, multiple sclerosis, pseudo-obstruction, carbapenem-resistant Enterobacteriaceae (CRE) or Vancomycin-resistant Enterococci (VRE) infection, radiation-induced toxicity, multiple organ dysfunction, dysbiotic bowel syndrome, MRSA enteritis, Pseudomembranous enteritis, idiopathic thrombocytopenic purpura (ITP), and atopy. Despite FMT appears to be relatively safe and efficacious in treating a wide range of disease, its safety and efficacy in a usual clinical setting is unknown. More data is required to confirm safety and efficacy of FMT. Therefore, the investigators aim to conduct a pilot study to investigate the efficacy and safety of FMT in a variety of dysbiosis-associated disorder.

EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

The goal of this clinical trial is to propose a seamless intervention linking rapid bacterial isolate identification and antibiotic resistance gene detection and targeted antibiotic prescription to minimise time between infection onset and appropriate treatment in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales infections. This is an investigator initiated trial. The primary hypothesis is that these interventions will lead to improved clinical outcomes amongst patients with hospital-acquired bloodstream infection, hospital-acquired pneumonia or ventilator-associated pneumonia due to carbapenem non-susceptible Pseudomonas aeruginosa or Enterobacterales, compared to standard antibiotic susceptibility testing. Patients will be randomised to either a control or intervention arm. Patients randomised to the intervention arm will have relevant specimens analysed by rapid microbiological diagnostics and will have early availability of ceftazidime-avibactam if appropriate. Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics. Antibiotics will be available to these patients as per usual institutional practice.

Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients

The goal of this observational study is to investigate how bacterial populations from the intestine and mouth of patients change during the hospitalization period and evaluate if some populations of specific bacteria increase or decrease the risk of acquiring an infection or becoming colonized by pathogenic bacteria. Participants will have the following samples collected during enrollment: stool samples (maximum 2x/week), blood draws (1x/week), oral swab (1x/week).

Precise Treatment of Ceftazidime-Avibactam in Patients With CRO Infections Under the Guidance of TDM and PPK Model

The goal of this study is to evaluate the efficacy and safety of ceftazidime-avibactam(CAZ-AVI) in the treatment of critically ill patients with carbapenem-resistant organisms(CRO) infections (including dialysis patients and extracorporeal membrane oxygenation(ECMO) patients).