Ventilator Associated Pneumonia

Adults who are unconscious or severely ill and need a breathing tube connected to a ventilator are at high risk of developing a lung infection (pneumonia) within the first few days in the intensive care unit. This early pneumonia affects up to 30 to 50 % of certain high-risk patients, prolongs the time on the ventilator and in hospital, and increases the use of antibiotics. Two strategies are commonly used today to try to prevent this infection: a short, three-day course of an intravenous antibiotic, and removal of secretions from the airway with a sterile suction catheter. Both have limitations - antibiotics can favour the growth of resistant bacteria, and catheter suctioning is uncomfortable and may injure the airway. PIRÁMIDES is a small (60-patient) pilot study that compares the current practice with two non-invasive, mechanical alternatives for keeping the airway clear: a continuous low-pressure suction system built into a special breathing tube, and a device that produces a gentle, programmed "artificial cough" through the ventilator. Adult patients who are intubated for severe trauma, severe brain injury, stroke, resuscitated cardiac arrest or other causes of decreased consciousness are randomly assigned, in equal numbers, to one of the three approaches and followed for 14 days, with a final visit at day 90. The main goal is to find out which of the three strategies best prevents early pneumonia, and which provides the best overall result for patients when survival, severity of infection, need for additional antibiotics and side effects are considered together. To make these comparisons as fair as possible in an open-label study, an independent committee of doctors not involved in patient care reviews each suspected pneumonia case without knowing which strategy the patient received. The results will help design a larger trial to confirm which approach is safest and most effective for preventing early pneumonia in critically ill patients on a ventilator.

The primary objective of the AMIVAT trial is to assess whether a 5-day course of inhaled amikacin, compared to placebo, reduces the incidence of progression to ventilator-associated pneumonia (VAP) at day 28 in intensive care unit (ICU) patients with ventilator-associated tracheobronchitis (VAT). Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT.

Diagnosis of VAP relies on a set of non-specific clinical, biological, and imaging criteria. Understanding host-pathogen interactions and the mechanisms of deregulations leading to infection of pulmonary tissue appears essential. The aim is to qualitatively describe the B lymphocyte populations present in the pulmonary microenvironment of patients admitted to intensive care and requiring invasive mechanical ventilation

The goal of this clinical trial is to learn if nebulized colistimethate sodium can prevent pneumonia in ventilated children. The main question it aims to answer is: • Does nebulized colistimethate sodium lower the number of times participants develop ventilation associated pneumonia? Researchers will compare nebulized colistimethate sodium to a placebo (a look-alike substance that contains no drug) to see if nebulized colistin works to prevent ventilation associated pneumonia in children. Participants will: * Take nebulized colistimethate sodium or a placebo twice a day for a maximum of 7 days. * Will be followed to check for pneumonia occurrence while they are on mechanical ventilation.

The goal of this observational clinical trial is to learn about the role white blood cells (macrophages) play in lung inflammation in people with Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are: 1. How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other? 2. What roles do the cells that live in the lungs (macrophages) play in turning off inflammation? How does their role differ from other cells that are called to the lung to help repair injury (recruited macrophages)? 3. Will more frequent testing of lung cell samples help reduce the time it takes to start treatment for ventilator-associated pneumonia (VAP) and therefore reduce the rates of initial therapy failure? Participants will be in the intensive care unit (ICU) on a mechanical ventilator (machine that helps patients breathe) because they have ARDS or are on a mechanical ventilator for some other reason (control group). The following will happen: 1. Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation. 2. A lung specialist (pulmonologist), a member of Dr. Janssen's research team, or respiratory therapist will place small amount of saline into the lung using a long catheter going through the breathing tube. 3. The fluid will be removed with suction and will be sent to the laboratory for testing. 4. This will be repeated two more times over the course of 10 days, or less if participants are taken off of the ventilator. The procedure will be performed no more than three times. 5. Two nasal brushings will be taken from the participants' nose. 6. Approximately 3 tablespoons of blood will be removed by putting a needle into the participants vein. This is the standard method used to obtain blood for tests. A total of 9 tablespoons will be taken for research purposes over the course of this study 7. Data including the participants age, sex, severity of illness, and other medical conditions will be recorded to determine how these can affect the white blood cells. 8. If bacteria are isolated from the fluid in the participants lung, the participants' physician may choose to place the participants on antibiotics to treat an infection. 9. A follow-up phone call may be made by a member of the research team after discharge from the hospital. At this time, the participant may be invited to participate in the Post-ICU clinic at National Jewish Health.

Clinical Trial The goal of this clinical trial is to learn whether different enteral feeding cycles (18-hour, 20-hour, or standard 24-hour continuous feeding) improve outcomes for critically ill ICU patients who need tube feeding. It will also look at tolerance, nutrition delivery, and safety. The main questions it aims to answer are: Do shorter feeding cycles (with fasting windows) reduce ICU length of stay? Do they lower the risk of infections like ventilator-associated pneumonia? How do they affect calorie delivery, blood sugar control, and gastrointestinal tolerance? Researchers will compare: Continuous 24-hour feeding (standard care) 20-hour feeding with a 4-hour fasting window 18-hour feeding with a 6-hour fasting window Participants will: Be critically ill adults in the ICU who require at least 7 days of enteral feeding Be randomized to one of the three feeding schedules Receive daily monitoring of calories, protein, blood sugar, and GI tolerance Have outcomes measured, including ICU length of stay, infections, metabolic control, and feeding tolerance

The use of corticosteroids in patients with severe community pneumonia, bacterial infection which kills lots of patients around the world, reduces the mortality of this infection. However, there are no studies with this type of drug regarding hospital-acquired pneumonia. This is the first multicenter randomized trial to test hydrocortisone plus standard therapy in critical care patients with nosocomial pneumonia. This intervention is inexpensive and may improve the outcome of those patients, besides having an acceptable side effects profile.

Almost 90 out of 100 people carry herpes simplex viruses (HSV). Once a person has been infected with the herpes viruses, he or she can't get rid of them for the rest of her/his life. For the most part, the viruses are in a dormant state. Only when the immune system is weakened, for example in the case of a serious illness or stress, are the viruses reactivated. They then mainly cause cold sores, which are harmless for healthy people and usually heal without therapy. However, especially in people with a weakened immune system, HSV can also cause serious infections, such as meningitis. In almost every second mechanically ventilated patient in intensive care who has pneumonia, HSV can be detected in the respiratory tract. This is caused by reactivation of the viruses as a result of the severe underlying disease and stress during intensive care therapy. Whether treatment of the herpes viruses (e.g. with acyclovir) is necessary in this situation and helps the patients to cure has not been clarified, especially as acyclovir can also cause side effects such as a deterioration in kidney function. Currently, the physicians decide to treat the herpes viruses in about half of the patients. Several studies have shown that patients for whom the physician decided to treat the viruses survived more often. However, all of these studies looked at the course of the disease only retrospectively and thus are subject to many biases (including physician selection of who receives treatment, missing data). A definitive conclusion as to whether herpesvirus therapy can be recommended cannot be drawn without doubt from these studies. Therefore, the investigators would like to investigate in a randomized controlled trial, i.e. patients are randomly assigned to the experimental (therapy of herpesviruses) or control group (no therapy of herpesviruses), the effect of therapy with acyclovir on survival in ventilated intensive care patients with lower respiratory tract infection (pneumonia) in whom a large amount of HSV was found in the respiratory tract. The goal of the study is to provide clarity on whether therapy will help patients recover.

Advanced stages of the response to life-threatening infection, severe trauma, or other physiological insults often lead to exhaustion of the homeostatic mechanisms that sustain normal blood pressure and oxygenation. These syndromic presentations often meet the diagnostic criteria of sepsis and/or the acute respiratory distress syndrome (ARDS), the two most common syndromes encountered in the intensive care unit (ICU). Although critical illness syndromes, such as sepsis and ARDS, have separate clinical definitions, they often overlap clinically and share several common injury mechanisms. Moreover, there are no specific therapies for critically ill patients, and as a consequence, approximately 1 in 4 patients admitted to the ICU will not survive. The purpose of this observational study is to identify early patient biologic factors that are present at the time of ICU admission that will help diagnose critical illness syndromes earlier, identify who could benefit most from specific therapies, and enable the discovery of new treatments for syndromes such as sepsis and ARDS.

PROACT study aims to resolve uncertainties to influence actual practice guidelines or public health policing regarding VAP prevention in ICU by using probiotics administration. Multi-trauma patients with a head injury OR stroke or brain haemorrhage patients without any sign of aspiration and lung infection will be enrolled and randomized to either placebo or probiotic treatment to assess if VAP and mortality can be reduced in the interventional group.

This study is designed to investigate the impact of a constructivist education program on nurses and cleaning personnel regarding the preventive care bundle for the prevention of ventilator-associated pneumonia in the intensive care unit.

Ventilator-associated pneumonia (VAP) remains one of the main nosocomial infections acquired in the intensive care unit (ICU). VAP is pneumonia occurring 48 hours after intubation. Today, bronchoalveolar lavage (BAL) is used for microbiological diagnosis, with bacterial culture and antibiotic susceptibility results within 48 to 72 hours. Multiplex PCR can detect DNA of a number of bacteriae, as well as the presence of resistance genes. However, its clinical value in the ICU remains to be demonstrated. We think that the use of multiplex PCR with a panel adapted to the microbiology of VAP, could be an interesting method for clinicians in ICU.

Critically ill patients who (1) are not able to maintain their airway, (2) cannot breathe on their own, or (3) both, are ones who often require tracheal intubation and support from a breathing machine (mechanical ventilator). When the patient is ready to be liberated from the mechanical ventilator because the initial insult for intubation has been resolved, the patient is screened using the readiness to wean test in preparation for extubation. As the patient passes this screening, a spontaneous breathing test (SBT) is initiated. Currently, there are many debates surrounding which SBT technique is most favorable. At Toronto General Hospital, the clinical team uses a zero-end expiratory pressure (ZEEP) trial. Once the patient successfully passes their SBT they are then extubated. The patient will undergo a spontaneous breathing trial of continuous positive airway pressure (CPAP) of 5 cmH2O and ZEEP, in which time the investigators will be using a new technology called electrical impedance tomography (EIT), to study and compare the end expiratory lung volume (EELV); investigators will use an esophageal catheter to measure and monitor pressures in the lung, and also assess the patient's work of breathing. This will be repeated once the patient has been extubated safely.

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment and for patients treated for ventilator associated pneumonia (VAP). Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP. Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP). The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms: Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure. Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines.

Efficacy of cotrimoxazole as a de-escalation treatment for adult patients Ventilator-Associated Pneumonia in intensive care unit Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP

Premature infants are susceptible to complications related to infrequent and non-standardized oral care. Although the benefits of frequent standardized oral care are known to reduce oral dysbiosis (increased level of potentially pathogenic bacteria) and its associated complications in critically ill adults leading to established evidence-based guidelines, no such information exists for VLBW infants. The proposed study will prospectively follow 168 VLBW infants for 4 weeks following birth.

Little is known about how lung mechanics are affected during the very early phase after starting mechanical ventilation. Since the conventional method of measuring esophageal pressure is complicated, hard to interpret and expensive, there are no studies on lung mechanics on intensive care patients directly after intubation, during the first hours of ventilator treatment and forward until the ventilator treatment is withdrawn. Published studies have collected data using the standard methods from day 1 to 3 of ventilator treatment for respiratory system mechanics, i.e. the combined mechanics of lung and chest wall. Consequently, information on lung mechanical properties during the first critical hours of ventilator treatment is missing and individualization of ventilator care done on the basis of respiratory system mechanics, which are not representative of lung mechanics on an individual patient basis. We have developed a PEEP-step method based on a change of PEEP up and down in one or two steps, where the change in end-expiratory lung volume ΔEELV) is determined and lung compliance calculated as ΔEELV divided by ΔPEEP (CL = ΔEELV/ΔPEEP). This simple non-invasive method for separating lung and chest wall mechanics provides an opportunity to enhance the knowledge of lung compliance and the transpulmonary pressure. After the two-PEEP-step procedure, the PEEP level where transpulmonary driving pressure is lowest can be calculated for any chosen tidal volume. The aim of the present study in the ICU is to survey lung mechanics from start of mechanical ventilation until extubation and to determine PEEP level with lowest (least injurious) transpulmonary driving pressure during ventilator treatment. The aim of the study during anesthesia in the OR, is to survey lung mechanics in lung healthy and identify patients with lung conditions before anesthesia, which may have an increased risk of postoperative complications.

The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 gram three times a day vs 1-hour infusion of 2 gram three times a day.

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.