Infections

All Conditions

Symptoms and General Pathology

Rare Diseases

Critical Illness

Communicable Diseases

Sepsis

Toxemia

Cross Infection

Disease Attributes

Iatrogenic Disease

Oculocerebral Syndrome With Hypopigmentation

performance of the NGS-based identification technique in comparison with the conventional culture-based one, for the same indwelling device biofilm sample

indwelling device biofilm identification

Luminita Smaranda Iancu, Professor

Ioana Grigoras, Professor

Olivia Simona Dorneanu, Assoc Prof

Catalina Lunca, Assist Prof

Teodora Vremera, Assist Prof

Stefania Brandusa Copacianu, MD, PhD

Iuliu Ivanov, PhD

Healthcare associated infections linked to the use of indwelling medical devices increase hospital morbidity, mortality and the Intensive Care treatment costs. The essential strategy for mitigating these consequences are prompt source identifcation and control, with appropriate antimicrobial therapy initiation as soon as possible. Removing the source is one of the golden rule for infection control. Early identification of the responsible germs is the other major guiding element for the appropriate anti-infectious treatment.

Despite multiple detection/identification methods, there are no clear recommendations for biofilm identification in clinical practice. The gold standard method is bacterial/fungal culturing, with disadvantages related to late results, especially for slow growing, fastidious germs or related to the existence of uncultivable strains.

In order to obtain more sensitive, specific results and to increase the chances of better biofilm characterization, in the present study the investigators compare biofilm identification results obtained by standard cultivation methods with those by DNA amplification and next generation gene sequencing. The studied biofilm is associated to four criticallly ill oncological patients indwelling devices (endotracheal tube, central venous catheter, arterial catheter and urinary catheter).

According to Regional Institute of Oncology, Iasi protocols, all septic patients with the need of invasive ventilatory support (endotracheal intubation), have concomitantly inserted a CVC, an AC and a UC, as standard of care. All patients undergo the protocol for the management of suspected/proven sepsis: initial resuscitation, specimen collection for microbiology/molecular biology tests, empirical/targeted anti-infectious treatment, source control, multiple organ support and treatment of the underlying disease/comorbidities. All RIO patients are screened for nasal, pharyngeal and rectal pathogen colonization at the time of hospital/ICU admission.

Informed consent - During the first 24 hours of ICU admission, all eligible patients will receive written information about the study: its implementation, aims, expected advantages and possible risks, and they will be asked to sign an informed consent. If the patient is unable to give consent at ICU admission due to pathological or drug-induced acute alteration of consciousness, a legal representative may give authorization. Once the participant regains the decision capacity, the individual will be asked to confirm or withdraw consent.

Swab sampling - The nasal, pharyngeal and rectal screening swab sampling is collected according to standard methods. In addition to this standard screening, in the first 24 hours of ICU admission cutaneous samples from the groin area of enrolled patients will be obtained, with sterile Copan eSwabTM swabs, a product recommended for aerobic, anaerobic and fastidious microbial agents.

Biofilm sampling and transport - The extraction of the four ID (ET, CVC, AC, UC) will be performed when the clinical condition of the patient dictates it (suspected catheter infection/no further need due to improvement or death). These devices will be extracted by medical ICU personnel, only at the indication and according to the medical judgment of the clinician, without being influenced by the patient's study participation.

Microbiological processing and analysis of the biofilm - Microbiological analysis will be performed by standard method: sample seeding on standard culture media, then biochemical identification test and AST according to CLSI standards and guidelines using MicroScan Walk Away 40 plus®, Beckmann Coulter automatic system compatible pannels.

Molecular biology processing and analysis of the biofilm - After complete sample collection, gene sequencing of the variable regions V3-V4 16S rRNA gene will be performed using Illumina MiSeq® Next Generation Sequencer System.

Biofilm from four medical devices: endotracheal tube, arterial catheter, central venous catheter and urinary catheter.

Indwelling Device-associated Biofilms

Indwelling Device-associated Biofilms in Oncological Critically Ill Patients

Patient report form, patient microbiological study sheet, patient device study sheet.

The detection/identification of biofilm-associated pathogens using Next Generation Sequencing (NGS) technique compared with standard microbiological diagnosis.

Identification of pathogens involved in ID biofilm formation (ET, CVC, AC, UC) in the critically ill oncological patients.

Comparison of the biofilm-associated pathogens with those identified in currently used biological samples (tracheal aspirate/bronchoalveolar lavage, blood culture, urinary culture, surgical wound swab, etc.) collected from the same patient.

Correlations between biofilm-associated pathogens and patient clinico-biological data:

* nasal, pharyngeal, rectal and skin pathogen screening;
* associated risk factors: neutropenia, chemo/radiotherapy, corticosteroid treatment, previous anti-infectious therapy;
* ID exposure time;
* biological markers of inflammation;
* diagnosed infection: respiratory tract infection, urinary tract infection, bloodstream infection, surgical site infection, sepsis of unknown origin, etc.;
* severity scores: Sequential \[Sepsis-Related\] Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score;
* ICU and hospital LOS;
* patient's outcome: survival/death;

Grigore T. Popa University of Medicine and Pharmacy

Assistant lecturer, MD

Neoplasms

Digestive System Diseases

Adenoma

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anti-Infective Agents

All Drugs and Chemicals

Herbal and Botanical

Metronidazole

Fosfomycin

Anti-Bacterial Agents

Antiprotozoal Agents

Antiparasitic Agents

Cola

14 patient with right-sided colon cancer receive intervention before the hemicolectomi.

both arms of this study use the same intervention.

14 patient with right-sided colon adenoma receive intervention before the endoscopic mucosa resection.

both arms of this study use the same intervention.

therapeutic endoscopy where the two drugs: metronidazole and fosfomycin disodium are sprayed through out the right colon section (from caecum to right colon flexure). This intervention is going to be performed on patients in both track 1 and track 2a.

therapeutic endoscopy with metronidazole and fosfomycin disodium

Astrid LB Bennedsen, M.D.

Ismail Gögenur, DMSc, MD,

Peter Vilmann, DMSc, MD

Clinical studies have shown that patients with right-sided colon cancer have reduced progression-free and overall survival compared to patients with left-sided colon cancer. At the same time, patients with right-sided colon adenomas have a higher risk of developing interval cancers after endoscopic mucosal resection. Dysbiosis and known bacterial drivers play a significant role in the carcinogenesis of colorectal cancer, and may contribute to the growth of adenomas. Clinical studies have found biofilm formation and positive staining for Fusobacterium nucleatum (FN) in almost all right-sided colon cancers and adenomas. The composition of bacteria also in the normal mucosa in these two groups of patients has been found to be different from healthy controls.

Endoscopic preoperative antibiotic local treatment of the biofilm and tumors would theoretically result in decreased tumor mass, recovery of the mucosa, and a normalization of the immune response in the treated section of the colon. The oral administration of the antibiotic metronidazole in mice has shown to lower the tumor load (FN-positive xenograft tumors) and decrease in intratumoral abundance of the pro-carcinogenic bacteria, FN.

The aim of this study is to investigate the effect of local antibiotic treatment with fosfomycin and metronidazole on tumor characteristics and the colonic biofilm in patients with right-sided colon cancer or right-sided colon adenomas. This is a clinical proof-of-concept intervention study, and the investigators are to our knowledge the first group to look into local antibiotic treatment of biofilm in patients with colon cancer or colon adenoma. It is based on a non-randomized trial design with an open label single group assignment. There are two tracks depending on the pathology of the tumor: 1) patients with right-sided colon cancer; 2a) patients with right-sided colon adenoma. The intervention is a therapeutic endoscopy where the antibiotics fosfomycin and metronidazole are sprayed throughout the right colon section from caecum to the right colon flexure (100ml of gel contains 800mg of fosfomycin and 200mg of metronidazole). Patients will be included prospectively from the surgical department of Herlev University Hospital and Zealand University Hospital once having received oral and written information, followed by signing the consent. There will be a retrospective cohort of patients with colon adenoma from 2018 (track 2b). The investigators will retrieve the archived adenoma tissue as control tissue. In Clinical Trial, Track 1 and Track 2a will be registered as two different arms that use the same intervention, but the results from each arm later on is going to be reported in separate publications.

The same intervention will apply to both arms of this study, the only difference is the patient group which receives the treatment.

In Clinical Trial, Track 1 and Track 2a will be registered as two different arms, but the results from each arm later on is going to be reported in separate publications.

Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma (MEFO-trial)

Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma: a Clinical Proof-of-concept Intervention Study MEFO Trial

A quantitative change in the bacterial biofilm adherent to the colonic epithelium of the resected colon adjusted for baseline level found before the intervention through fluorescence in situ (FISH) technique. The specific measurement variable is biofilm depth in μm. The method of aggregation will be means.

A quantitative change in the bacterial biomass adherent to the colonic epithelium of the resected colon adjusted for baseline level found before the intervention through fluorescence in situ (FISH) technique. The specific measurement variable is biofilm mass in ng/cm\^2. The method of aggregation will be means.

- The determination of differences in translational markers present in the resected tumor tissue adjusted for the level seen at the baseline (the therapeutic colonoscopy) through a principal component analysis (PCA). The translational markers of interest are tumor markers, markers of the microenvironment and the immune response. The analyses will be performed using the PanCancer IO 360TM Gene Expression Panel (nanoString).

- The determination of a change in the bacterial composition adjusted for the bacteria found at baseline before the intervention through fluorescence in situ (FISH) technique and sequencing with Metagenome.

Differences in the presence of known bacterial drivers such as Fusobacterium nucleatum, Enterococcus faecalis, Bacteroides Fragilis, Escherischia coli, and Porphyromonas in the tumor samples from preoperative biopsies and the resected colon.

Differences in gene expression in the normal mucosa from preoperative biopsies and the resected colon using the PanCancer IO 360TM Gene Expression Panel (nanoString).

Differences in gene expression in the preoperative and operative blood samples determined by the nCounter® PanCancer Immune Profiling Panel (nanoString).

Assessment of the immunological response using immunoscore. A binary outcome of either high or low immunoscore

The pathological assessment of tumor: tumor type, grade of dysplasia, TNVM-stage, MSI- status.

A microbiological assessment of the biofilm present on the tumor in track 1. This will be reported as a binary outcome.

The pathological assessment of the normal mucosa of the right hemicolon: presence of biofilm, dysplasia and inflammation.

Safety assessment of the spraying of the right hemicolon with fosfomycin/metronidazole gel. This will be assessed through adverse events reported at least 19 days after the intervention (postoperative day 14).

Differences in gene expression in the normal mucosa from preoperative biopsies and the operative biopsies using the PanCancer IO 360TM Gene Expression Panel (nanoString).

Differences in gene expression in the tumor tissue from the mucosal resection compared with archived FFPE tumor tissue from patients with colon adenoma using the PanCancer IO 360TM Gene Expression Panel (nanoString).

Differences in gene expression in the preoperative blood samples and the blood samples taken on the operation day using the nCounter® PanCancer Immune Profiling Panel (nanoString).

The pathological assessment of polyp using the Paris Classification and the Lateral Spreading Tumor Classification to determine tumor type.

The pathological assessment of polyp: size

an assessment of the immunological response via immunoscore

The microbiological assessment of polyp: an assessment of the biofilm present on the polyp. This will be reported as a binary outcome.

Assessment of the spraying of the right hemicolon with fosfomycin/metronidazole gel. By collecting reported adverse events at least 19 days after the intervention (postoperative day 14).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Indwelling Device-associated Biofilms	NCT04328818	Oncology Critical Illnes... Sepsis Hospital Infect...	indwelling devi...	18 Years -	Grigore T. Popa University of Medicine and Pharmacy
Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma (MEFO-trial)	NCT04312360	Right-sided Col... Right-sided Col...	therapeutic end...	18 Years -	Zealand University Hospital

Spots Global Cancer Trial Database for biofilm

Every month we try and update this database with for biofilm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for biofilm

Every month we try and update this database with for biofilm cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for biofilm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.