Decreasing Antibiotic Use in Infants With Suspected Ventilator-associated Infection

Microbial Colonization Clinical Trial

— VAIN2  

Official title:

Decreasing Antibiotic Use in Infants With Suspected Ventilator-associated Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03041207
• Other study ID #: HM20009140
• Status: Completed
• Start date: March 20, 2017
• Est. completion date: April 30, 2019

Study information

• Verified date: July 2019
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a prospective study with three specific aims: (1) To convene a consensus conference to develop a guideline for antibiotic use in infants (age < 3 yrs) with suspected ventilator-associated infection; (2) To evaluate outcomes before and after implementation of the antibiotic guideline; (3) To evaluate changes in the tracheal microbiome over the course of mechanical ventilation

Description:

In 2011 the Centers for Disease Control (CDC) estimated antibiotic-resistant infections resulted in $20 billion in excess healthcare costs and more than 100,000 unnecessary deaths in the U.S. alone. Ventilator-associated infections (VAI) are the most commonly diagnosed hospital-acquired infections in the pediatric intensive care unit (PICU) and account for more than half of all antibiotic use. We believe the diagnosis is often in error and that much of the antibiotic use is unnecessary. Initiating broad-spectrum antibiotics is routine when VAI or other infection is suspected in the child on mechanical ventilation, but our data show when all other cultures are negative at 48-72 hours antibiotics are frequently still continued based on identification of bacteria in respiratory secretion cultures. The investigators have previously shown, however, that identification of bacteria in respiratory secretion cultures is common in asymptomatic children and continuing antibiotics on the basis of a "positive" respiratory secretion culture is not associated with a shorter hospital stay or improved survival.

Antibiotics are not benign. Antibiotics are expensive, have disproportionate adverse effects in younger children, often require placement of catheters that are themselves potential sources of infection, and their overuse has been associated with increasing resistance worldwide. Antibiotic exposure in young children has been associated with increased risk for obesity, types 1 and 2 diabetes, inflammatory bowel diseases, celiac disease, allergies, and asthma. Mouse studies have found that early antibiotic exposure disrupts the development of the early-life gut bacterial composition (microbiome), leading to metabolic perturbations that affect fat deposition and may alter normal immunologic development.

There is no diagnostic test for VAI and distinguishing tracheal bacterial colonization from actual infection is not straightforward. The normal lung is essentially sterile but placement of an endotracheal tube (ETT) compromises the lung's ability to clear aspirated secretions and allows a direct route for bacterial contamination from the mouth and throat. The resultant tracheal bacterial composition (the "microbiome") is largely unstudied but preliminary research suggests it consists of small numbers of a wide diversity of bacteria originating from the mouth. Loss of this bacterial diversity in conjunction with proliferation of pathological bacteria is thought to herald the conversion from colonization to infection.

The investigators believe that a positive respiratory culture alone in the absence of other indicators of infection is insufficient justification for continuing antibiotics and, consequently, much of the antibiotic use in VAI is both unnecessary and potentially harmful. To critically evaluate this belief and potentially decrease the use of unnecessary antibiotics we propose the following:

Aim 1: To develop a guideline to assess the likelihood of VAI and discontinue antibiotics when the risk is judged to be low Hypothesis 1.1: Using an iterative process PICU doctors can reach consensus on criteria to assess the likelihood of VAI and discontinue antibiotics when the risk of VAI is judged to be low

Aim 2: To assess the efficacy and safety of discontinuing antibiotics in children judged to have a low risk of VAI Hypothesis 2.1: Discontinuing antibiotics at 48-72 hours in children judged to have a low risk of VAI will result in fewer total days on antibiotics with no difference in survival, numbers of subsequent infection episodes, duration of need for mechanical ventilation and length of stay in the PICU compared to care prior to the implementation of the guideline.

Aim 3: To describe the longitudinal changes in the tracheal bacterial composition (the "microbiome") in children on mechanical ventilation Hypothesis 3.1: Loss of diversity in the tracheal microbiome will predate clinical signs and symptoms of VAI.

Hypothesis 3.2: Emergence of a dominant bacterial pathogen in the tracheal microbiome will be associated with clinical signs and symptoms of VAI.

Decreasing unnecessary antibiotic use has important implications for public health. Pediatric intensive care medicine is running out of effective antibiotics while also exposing our children to antibiotic risks, many of which are only now beginning to be understood. Avoidance of unnecessary antibiotic exposure in young children is critical and would be facilitated by a rational guideline for assessment of the risk and appropriate treatment for suspected VAI. As VAI is the most common reason for antibiotic use in the PICU, it is an obvious target for more careful antibiotic stewardship. Better understanding of the normal tracheal microbiome after placement of an endotracheal tube would also inform future decisions regarding appropriate antibiotic use when VAI is suspected. The most effective means of decreasing antibiotic resistance is avoidance of unnecessary use.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 555
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Years

Eligibility

Inclusion Criteria:

• Age newborn -- 3 years in the Pediatric ICU

• on invasive mechanical ventilation > 48 hours

• evaluation for ventilator-associated infection that includes respiratory secretion cultures and microscopic evaluation of the gram-stained specimen

• antibiotics initiated for suspected ventilator-associated or other infection

Exclusion Criteria:

• Immune compromise --Other positive cultures (blood, urine, etc.) for which antibiotic continuation is appropriate

Related Conditions & MeSH terms

• Communicable Diseases
• Cross Infection
• Infection
• Microbial Colonization
• Nosocomial Infections in Children
• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Behavioral:
• Development and implementation of an antibiotic guideline
A consensus conference will develop and then implement a guideline for stopping vs. continuing antibiotics in infants with suspected ventilator-associated infection

Locations

Country	Name	City	State
Canada	Centre hospitalier universitaire Sainte-Justine	Montréal	Quebec
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston Hospital	Atlanta	Georgia
United States	Children's Hospital of Buffalo	Buffalo	New York
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University Hospitals Rainbow Babies & Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	University of Miami Health System - Holtz Children's Hospital	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Children's Hospital of Richmond at VCU	Richmond	Virginia
United States	St. Louis Children's Hospital - Washington University	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington
United States	Banner University Medical Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	The Gerber Foundation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pediatric ICU-free days at 28 days	28 - number of days in PICU (death = 0 free days)	28 days after study enrollment
Secondary	Antibiotic days in PICU	total number of antibiotic days with each antibiotic on each day = 1 antibiotic day (e.g., 3 antibiotics in one day = 3 antibiotic days)	28 days after study enrollment
Secondary	Ventilator-free days at 28 days	28 - days on mechanical ventilation in PICU (death = 0 free days)	28 days after study enrollment
Secondary	Infection and sepsis episodes	The number of infection and/or sepsis episodes after study enrollment	28 days after study enrollment