Editor’s Note:
Precision treatment starts with accurate diagnosis. The clinical diagnosis of ventilator-associated pneumonia (VAP) is challenging, with a high misdiagnosis rate leading to excessive antibiotic use. At the recent 2023 IDWeek conference in the United States, a clinical trial was reported that utilized a bundled approach to VAP diagnosis and management. The results showed that it is safe and significantly reduces the respiratory culture positivity rate and antibiotic usage. Below, Professor Wang Yimin and his team from the China-Japan Friendship Hospital introduce and comment on this study.
Research Introduction
Ventilator-associated pneumonia (VAP) is often overdiagnosed and is a major driver of excessive antibiotic use in the Intensive Care Unit (ICU). Antibiotic stewardship programs have successfully been applied to reduce the overdiagnosis/overtreatment of various clinical syndromes, but this approach has not been extended to VAP. This study aimed to assess the safety, feasibility, and effectiveness of a new type of Diagnosis Intervention Care Bundle (DSI-CB) for VAP.
The DIVA trial (NCT05176353) was a pilot/feasibility trial conducted in two ICUs at the University of Michigan from February 2022 to February 2023. Using an interrupted electronic health record clinical decision support tool to modify the microbiology laboratory workflow, the DSI-CB targeting respiratory culture testing pathways was continuously implemented in the study ICUs. Consultations on the use of DSI-CB were provided to providers through monthly email reminders during the trial rollout and at bimonthly educational meetings. Negative binomial regression was used to compare the ratios of predefined primary safety and secondary effectiveness outcomes between the post-intervention study cohort and a historical control of the 5 years before the intervention. Interrupted time series analysis was used to assess ICU antibiotic usage rates (ICU-AURs) to illustrate time trends.
A total of 1810 ICU patients were included in the implementation of DSI-CB, with 29% of patients meeting the criteria for DSI-CB use. Of the eligible patients, 77% used DSI-CB. Demographics, comorbidities, and measurements of acute illness severity were similar before and after the intervention.
The results showed that the implementation of DSI-CB was not associated with increased primary adverse safety outcomes. There were no significant differences in mortality (P=0.86), mechanical ventilation use (P=0.59), or the incidence of ventilator-related adverse events (P=0.05) before and after the intervention.
Following the implementation of DSI-CB, the positivity rate of respiratory culture significantly decreased by 16% (P<0.01), and the duration of broad-spectrum antibiotic usage (Days of Therapy, DOT) significantly decreased (P=0.03).
Dr. Yi-min Wang Commentary:
Ventilator-associated pneumonia (VAP) refers to pneumonia occurring in patients receiving mechanical ventilation via endotracheal tubes or tracheostomy tubes after 48 hours. Compared to other forms of hospital-acquired pneumonia, VAP typically involves more drug-resistant pathogens and worse clinical outcomes, making it a challenging issue for clinicians.
The first challenge is the diagnostic problem. Although the clinical concept of VAP has been around for a while, the accuracy of diagnosis remains limited based on current diagnostic criteria. Existing diagnoses are based on chest imaging, along with a few clinical symptoms, signs, and laboratory test results. However, these symptoms, signs, and chest imaging findings are not sensitive and specific diagnostic markers since they can all be caused by other respiratory conditions such as atelectasis, pulmonary embolism, pulmonary edema, and more. Achieving an accurate diagnosis of VAP is a highly challenging task. High rates of misdiagnosis of VAP (with reported misdiagnosis rates as high as 70% in the study) have led to unnecessary antibiotic use in clinical practice.
Therefore, in response to the current clinical dilemma, researchers optimized the diagnostic process simultaneously from three aspects: orders, sample collection, and reporting. Researchers used lower respiratory tract sample cultures as the starting point, strictly limiting microbiological testing to qualified bronchoalveolar lavage (BAL) samples to identify pathogenic microorganisms related to clinical symptoms, thereby reducing overdiagnosis and overtreatment of VAP. This design is understandable since there are currently no better alternatives for other diagnostic criteria such as fever, white blood cell count, purulent respiratory secretions, and optimizing imaging findings may be more complex (possibly requiring AI assistance). In contrast, focusing on improving pathogen diagnostic accuracy seems to be a more feasible optimization approach at this stage.
Based on the above considerations, the researchers designed a diagnostic intervention method to obtain reliable specimens through quantitative culture of lower respiratory tract secretions, aiming for a more accurate differentiation between infection and colonization. In fact, from the research findings, although the patient population in the experimental group had more severe conditions and a lower positive culture rate of respiratory samples, there was no difference in mortality between the two groups, and the rate of serious adverse events was lower. Additionally, this study revealed a significant reduction in the duration of broad-spectrum antibiotic use by optimizing the VAP diagnostic process.
This study addresses a long-standing medical challenge faced by clinicians, and its results are promising, even though it has not fundamentally resolved the issue of differentiating infection from colonization. The practical clinical value of this research still needs validation from real-world medical practice. The results of this study suggest that in the future, if there are better ways to distinguish whether respiratory sample isolates are due to infection or colonization, it could likely bring about significant changes in current diagnostic and therapeutic practices, ultimately benefiting patients.
Department of Respiratory and Critical Care Medicine
China-Japan Friendship Hospital (National Respiratory Medicine Center)
Department of Respiratory and Critical Care Medicine
China-Japan Friendship Hospital
