Probiotic Prophylaxis for Microbiome Modulation and VAP or Infections Prevention in Multitrauma Patients
Condition: Ventilator Associated Pneumonia; Infection; Trauma
MeSH terms: Infections; Communicable Diseases; Pneumonia; Pneumonia, Ventilator-Associated
Study type: Interventional

Summary: 
      Ventilator-associated pneumonia (VAP), is a type of pneumonia that develops more than 48
      hours after endotracheal intubation, is common in intensive care units (ICUs). It is
      estimated to be responsible for 27% to 47% of ICU-acquired infections.

      The pathogenesis of VAP is complex but typically involves colonization of the aerodigestive
      tract with pathogenic bacteria, the formation of biofilms, and microaspiration of
      contaminated secretions. Preventing carriage of potentially pathogenic micro-organisms from
      the aerodigestive tract is an infection control strategy used to reduce the occurrence of
      VAP. One novel intervention is the administration of prophylactic probiotics which restore
      non-pathogenic flora that compete with pathogens, modulate local and systemic immunity, and
      decrease intestinal permeability and thus can be beneficial in preventing nosocomial
      infections in critically ill patients. The role of the probiotics in preventing VAP in
      mechanically ventilated patients is inconclusive. Some evidence indicates that probiotics may
      reduce the incidence of VAP by inhibiting pathogen adhesion, improving gut mucosal barrier
      function, reducing bacterial translocation and up-regulating the immune system. Furthermore,
      guidelines remain inconclusive regarding the role of commensal oropharyngeal flora (COF) as a
      causative agent in VAP, mainly due to a scarcity of studies in this research field. However,
      there is evidence that COF may cause pulmonary infection, mostly in immunocompromised
      patients.
    

Detailed description: 
      The oropharyngeal swab will be collected on days 1, 3 and 7 after ICU admission and upon the
      occurrence of VAP or other infection. Nonbronchoscopic bronchoalveolar lavage (BAL) using a
      protected catheter will be collected on day 3 after ICU admission and upon the occurrence of
      VAP. Whole blood sample and stool sample will be collected on day 1 after ICU admission and
      upon the occurrence of VAP or other infection for microbiome analysis.

      As soon as the first sample of the oropharyngeal swab is collected, patients will be
      allocated to the "treatment" groups. Each patient will receive two capsules per day for 15
      consecutive days post admission. The content of one capsule will be suspended in 100ml tap
      water and administered by nasogastric tube or through), while the content of the other
      capsule will be suspended in sterile, water-based surgical lubricant and administered as a
      slurry to the oropharynx. The administration will be performed by a study nurse who was
      responsible for ascertaining that the whole prepared volume is given.

      The study protocol-mandated baseline data will include demographic information, medical
      history, and the APACHE II, SAPS II, NISS and SOFA score, and Operative POSSUM score (only
      cases undergoing surgical treatment).

      Additional information collected on a daily basis will include patient's clinical course with
      special emphasis on clinical signs of VAP or infections, type of chemoprophylaxis,
      endotracheal or tracheostomy tube cuff pressure, type of nutrition and bowel movement.
      Furthermore, duration of intubation, tracheostomy day after ICU admission, duration of
      mechanical ventilation, lengths of stay in the ICU and hospital, adverse events (related and
      non-related to probiotics administration) and mortality. Data recording will be extended up
      to 30 days after hospital admission (patient recovered, treated in ICU / department or
      death).

      Central venous line infection will be considered as positive when there is bacteremia with
      common skin commensal and positive catheter tip culture or exit site culture for the same
      organism.

      An ICU-acquired urinary tract infection will be deemed present if there are at least 103
      colony-forming units (cfu)/mL of 1 or 2 micro-organisms identified by urine culture in
      patients who develop a positive urine culture first identified 48 h or later after ICU
      admission.

      A superficial incisional infection (SSI) must meet the following criterion:

      Infection occurs within 30 days after the operative procedure and involves only skin and
      subcutaneous tissue of the incision and patient has at least 1 of the following:

        -  purulent drainage from the superficial incision

        -  organisms isolated from an aseptically obtained culture of fluid or tissue from the
           superficial incision

        -  at least 1 of the following signs or symptoms of infection: pain or tenderness,
           localized swelling, redness, or heat, and superficial incision is deliberately opened by
           the surgeon and is culture positive or not cultured. A culture-negative finding does not
           meet this criterion.

        -  diagnosis of superficial incisional SSI by the surgeon or attending physician.

      Intraabdominal trauma infection will be defined by the following:

        -  Temperature >38°C or <36°C

        -  White blood cell count >12 000/mm3 or <4000/mm3 or >10% immature bands

        -  Abdominal tenderness during clinical examination

        -  CT scanning compatible with positive findings for acute intraabdominal infection An
           antibiotics-related infection will be documented by the detection of toxins produced by
           C. difficile bacteria in a stool sample.

      Bacteremia will be defined as the presence of a recognized Gram(+) or Gram(-) pathogen or
      Candida spp cultured from one or more blood cultures and organism cultured from blood is not
      related to an infection at another site Sepsis is defined as life-threatening organ
      dysfunction caused by a dysregulated host response to infection.

      Organ dysfunction will be identified as an acute change in total SOFA score ≥2 points
      consequent to the infection.

      Patients with septic shock will be identified with a clinical construct of sepsis with
      persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum
      lactate level >2 mmol/L (18mg/dL) despite adequate volume resuscitation.
    

Intervention name(s): LactoLevure; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): The probiotic preparation will consist a combination of four probiotics: Lactobacillus acidophilus LA-5 1.75 × 109 CFU, Lactobacillus Plantarum 0.5 × 109 CFU, Bifidobacterium lactis BB-12 1.75 × 109 CFU και Saccharomyces boulardii 1.5 × 109 CFU per capsule (LactoLevure, UniPharma, Athens, Greece).; Placebo will consist of identical capsules of powdered glucose polymer
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The present study will be a multicenter, randomized, double-blind, placebo-controlled trial including data collected from 9 ICUs. Patients will be randomly assigned in a 1:1 ratio to receive probiotic or placebo treatment according to a computer-based table blinded to study investigators and physicians in charge.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: probiotics; VAP; microbiome; trauma; infections