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Rochester, MN
Dr. Afessa is Associate Professor of Medicine, Pulmonary and Critical Care Division, Mayo Clinic.
Correspondence to: Bekele Afessa, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905; e-mail: Afessa.Bekele{at}mayo.edu
Ventilator-associated pneumonia (VAP) is responsible for approximately half of the infections acquired in the ICU.1 Patients with VAP have longer ICU and hospital length of stay, with higher crude hospital cost and mortality rate compared to patients without VAP.23 Despite the importance of VAP and its clinical and financial implications, the absence of a "gold standard" for its diagnosis and the scarcity of outcome-based clinical trials had led to "pro and con" debates, at times opinionated.45 Although the First International Consensus Conference on the Clinical Investigation of Ventilator-Associated Pneumonia highlighted the need for research in the field, most of its recommendations were based on expert opinions, not on scientific evidence.6 In this issue of CHEST (see page 1791), Micek et al shows that the duration of antibiotic therapy can be shortened by implementing clinical guidelines for discontinuing antibiotics.
More than a decade has passed since the first international consensus conference on VAP. Despite progress in the field, the "gold standard" for the diagnosis of VAP has still eluded us. Even the histologic diagnosis of VAP is far from perfect, as evidenced by studies showing disagreement among pathologists.7 We have known for decades that the clinical criteria for the diagnosis of VAP lack adequate specificity.8 Realizing the futility of the pro and con debates in the absence of a diagnostic "gold standard," studies have focused on the impact of the diagnostic approaches on outcome. In addition to Johanson’s conventional clinical criteria, the Clinical Pulmonary Infection Score (CPIS) and criteria based on bronchoscopic and nonbronchoscopic sampling of lower respiratory tract specimen are used in guiding the management of VAP.89101112 In the last 5 years, several studies have described the impact of different approaches to VAP on patient outcome. Singh et al13 showed that management of suspected VAP based on the CPIS can decrease the antibiotic cost and the development of antimicrobial resistance and superinfection, without altering patient outcome. In the only adequately powered multicentered randomized clinical trial,14 in which clinical management strategy was compared with an invasive approach, consisting of the bronchoscopic sampling of lower airway secretions for quantitative culture, the latter was associated with a lower 14-day mortality, more rapid resolution of organ failure, and less antibiotic use.
Parallel to the progress regarding the optimal diagnostic approach, we have also seen observational studies addressing the use of antibiotics in VAP. In the last few years, we have learned that choosing an effective antibiotic from the outset, stopping antibiotics that are no longer needed (de-escalation), and rotating antibiotics are cornerstones in the management of VAP. There is ample clinical evidence suggesting that inadequate initial antibiotic treatment of critically ill patients with suspected infection is associated with increased morbidity and mortality.1516171819 In order to ensure the adequacy of the initial antibiotic coverage, clinicians often resort to multiple and broad-spectrum antibiotics. However, the initiation and continuation of multiple antibiotics can lead to the development of superinfection and antibiotic-resistant bacteria. Every attempt should be made to decrease VAP risk factors such as use of antibiotics in the absence of infection, or an overly cautious ventilator weaning strategy that leaves endotracheal tubes in place longer than they need to be. Simple and cheap preventive methods such as elevating the head of the patient’s bed should be applied. Clinicians should target their antibiotic coverage based on the local hospital epidemiology and individual patient characteristics. Narrowing antibiotic coverage when culture results are available and implementing antibiotic practice guidelines have also been suggested as strategies to reduce inadequate treatment and the development of antibiotic resistance.20
The optimal duration of antibiotic therapy for suspected or documented VAP is not known. Clinical responses to therapy for VAP occur within the first 6 days of antibiotic treatment.21 However, endotracheal colonization persists despite susceptibility to therapy, and acquired colonization usually occurs in the second week.21 Although most of us treat VAP with 7 to 21 days of antibiotics, our practice has not been based on evidence derived from prospective clinical trials. A recent randomized clinical trial22 of patients with documented VAP has shown that 8 days of antibiotic coverage has the same clinical efficacy as 15 days of treatment. In this issue Micek et al report the impact of an antibiotic discontinuation policy on patient outcome. They show that the duration of antibiotic therapy can be shortened by implementing clinical guidelines for discontinuing antibiotics. Specifically, antibiotics were discontinued if noninfectious etiology was identified or the signs and symptoms of VAP had resolved. They included patients without confirmed VAP, and their diagnostic approaches were not uniform for all their study subjects. Quantitative cultures of bronchoscopic BAL were obtained in some, but not all, study subjects. Although the study was prospectively designed, no sample size analysis was performed to determine the power of the study because the main intention of the study was internal quality improvement. However, the study was adequately powered for the primary outcome variable of interest, namely duration of antibiotic treatment.
Should we implement a shorter duration of antibiotic therapy for VAP based on recent results of randomized critical care trials? The medical literature addressing VAP is full of studies with conflicting results. Fortunately, the two studies addressing duration of antibiotic therapy for VAP complement each other.22 The study by Chastre et al22 showed that an 8-day vs 15-day course of antibiotics had the same outcome. Micek et al discontinued treatment as soon as the clinical findings of VAP had resolved. I plan to use a shorter duration of antibiotic treatment for VAP in my clinical practice. Since individual responses to treatment may vary depending on the underlying medical conditions and the pathogens causing the VAP, basing treatment duration on clinical assessment rather than adhering to a fixed treatment duration is appealing. The fact that the study by Micek et al was a quality improvement study does not lessen the quality of the article and its clinical implications. In fact, the absence of restrictions that usually characterize many randomized clinical trials and the inexpensive cost associated with the intervention may make the antibiotic discontinuation policy guideline of Micek et al suitable for implementation in most clinical practices.
References
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