Indwelling Device-associated Biofilms (BiofilmICU)

Indwelling Device-associated Biofilms in Oncological Critically Ill Patients

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis; Critical Illness; Oncology; Hospital Infection
• Intervention / Treatment: Diagnostic test: indwelling device biofilm identification

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• Romania
  • Iasi, Romania, 7--483
    • Regional Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive critical oncology patients, which meet all inclusion criteria and have no exclusion criteria, admitted to the Intensive Care clinic of the Regional Oncology Institute, Iasi, Romania.

Description

Inclusion criteria:

1. Signed informed consent;
2. Age ≥18 years;
3. Suspected/proven sepsis/septic shock (Supplemental file 2);
4. APACHE II score ≥10 (Supplemental file 3);
5. Predictable invasive ventilatory support ≥ 48 hours;
6. Patient estimated survival ≥ 4 days.

Exclusion criteria:

1. Patient/legal representative refusal;
2. Age <18 years;
3. Chronic psychiatric/neurological disease with impaired decision-making capacity;
4. Pregnancy;
5. Invasive ventilatory support < 2 days;
6. Death in less than 4 days after ICU admission.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The detection/identification of biofilm-associated pathogens	The detection/identification of biofilm-associated pathogens using Next Generation Sequencing (NGS) technique compared with standard microbiological diagnosis.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of pathogens involved in ID biofilm formation	Identification of pathogens involved in ID biofilm formation (ET, CVC, AC, UC) in the critically ill oncological patients.	through study completion, an average of 1 year
Comparison of the biofilm-associated pathogens with those identified in currently used biological samples	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.	through study completion, an average of 1 year
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.	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.	through study completion, an average of 1 year
Establishing clinico-biological correlations	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;	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Grigore T. Popa University of Medicine and Pharmacy
• Investigators: Principal Investigator: Luminita Smaranda Iancu, Professor, University of Medicine and Pharmacy "Grigore T Popa", Iasi, Romania; Study Director: Ioana Grigoras, Professor, University of Medicine and Pharmacy "Grigore T Popa", Iasi, Romania; Study Director: Olivia Simona Dorneanu, Assoc Prof, University of Medicine and Pharmacy "Grigore T Popa", Iasi, Romania; Study Director: Catalina Lunca, Assist Prof, University of Medicine and Pharmacy "Grigore T Popa", Iasi, Romania; Study Chair: Teodora Vremera, Assist Prof, University of Medicine and Pharmacy "Grigore T Popa", Iasi, Romania; Study Chair: Stefania Brandusa Copacianu, MD, PhD, Regional Institute of Oncology Iasi, Romania; Study Chair: Iuliu Ivanov, PhD, Regional Institute of Oncology Iasi, Romania

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2019
• Primary Completion (Anticipated): September 5, 2023
• Study Completion (Anticipated): October 5, 2025

Study Registration Dates

• First Submitted: March 27, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): March 31, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: biofilm; Next Generation Sequencing; critical; oncologic
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Iatrogenic Disease; Critical Illness; Cross Infection
• Other Study ID Numbers: GTPopaUMPIASI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Patient report form, patient microbiological study sheet, patient device study sheet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No