Probiotic Prophylaxis for Microbiome Modulation and VAP or Infections Prevention in Multitrauma Patients
Probiotic Prophylaxis for Microbiome Modulation and VAP or Infections Prevention in Multitrauma Patients
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.
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.
Inclusion Criteria:

 -  adults >18 and < 80 years oldmultitrauma patients with at least two organ-system
 injury

 -  intubated immediately after injury

 -  likelihood that the patient would require mechanical ventilation with an endotracheal
 tube (or tracheostomy) for >10 days

 -  life expectancy > 15 days

 Exclusion Criteria:

 -  investigators unable to obtain informed written consent from patients' relatives

 -  administer the first dose of the study drug within 24 hours of intubation

 -  pregnancy; lactation; immunosuppression; hematologic disease; prosthetic cardiac valve
 or vascular graft; cardiac trauma; history of rheumatic fever, endocarditis, or
 congenital cardiac abnormality; oropharyngeal mucosal injury; recent history of
 sinusitis and respiratory tract infection

 -  obesity [BMI > 40]

 -  administration of antibiotics for > 3 days before recruitment into the study

 -  administration of probiotics before recruitment into the study

 -  history of infection from Hepatis B or C and HIV

 -  administration of < 90% of the predicted doses of probiotics during the study period