© 2008 American Thoracic Society doi: 10.1164/rccm.200710-1482ED
A Bad Bug Takes on a New Role as a Cause of Ventilator-associated Pneumonia
Myeloma Institute for Research and Therapy Despite use of preventive strategies and significant advances in supportive care and antimicrobial therapy, ventilator-associated pneumonia (VAP) remains an important cause of morbidity and mortality (1). Although bacteria cause most VAPs, invasive pulmonary aspergillosis (IPA) is extremely uncommon, except when classical risk factors for aspergillosis (hematologic cancer, neutropenia, transplantation) are present. In this issue of the Journal (pp. 27–34), Meersseman and colleagues (2) report their findings using detection of Aspergillus galactomannan (GM) (cell wall constituent released during tissue invasion) in bronchoalveolar lavage (BAL) fluid (BAL-GM) for diagnosing VAP caused by Aspergillus spp. Upon diagnosis of pneumonia, 110 adults at risk for IPA underwent BAL for culture and GM detection, serum GM, and chest computed tomography (CT). Only 22% of patients were neutropenic and 67% had underlying diseases other than hematologic cancer, including cirrhosis and chronic obstructive pulmonary disease (COPD). Twenty-six patients (24%) developed histopathologically proven IPA. The diagnostic sensitivity and specificity of BAL-GM was 88 and 87%, respectively, compared with 42% sensitivity for serum GM. Serum GM and BAL culture remained negative in 11 patients (42%) in whom BAL-GM was positive. Chest CT was of limited diagnostic value. The findings of this prospective study, backed by an impressive 95% autopsy rate, underscore the increasingly important role that Aspergillus species play as a cause of VAP in apparently immunocompetent intensive care unit (ICU) patients (3–6). Indeed, 24% of patients developed IPA in absence of classical risk factors (2). A high index of suspicion for IPA should therefore be exercised when caring for such apparently immunocompetent hosts. Apparently immunocompetent hosts include recipients of low doses of corticosteroids and patients with conditions such as COPD, cirrhosis, transfusion-associated hemosiderosis, and diabetes mellitus (3, 7, 8). These patients may suffer additional transient insults to their somewhat weakened immune system, as a result of corticosteroid therapy for septic shock, sepsis-associated immunoparalysis, malnutrition, transfusions of allogeneic blood products, hemodialysis, or poorly controlled glycemia (1, 3). Classic immunosuppression as we know it is expanding to include apparently immunocompetent patients whose mild–moderate immune deficits are transiently worsened resulting in cumulative immunosuppression severe enough to cause life-threatening infections such as IPA. Diagnosing IPA in nonneutropenic ICU patients is challenging because of low index of suspicion and lack of validation of the diagnostic tools for aspergillosis in this setting. Diagnosis usually rests on a combination of clinical, radiologic, microbiologic, and histopathologic findings (8). However, clinical findings are notoriously difficult to characterize in mechanically ventilated patients and, unlike in neutropenic patients, lung CT has limited value because findings are nonspecific and may develop over preexisting atelectasis or acute respiratory distress syndrome (1, 3). Positive culture results are present in less than 50% and have poor predictive value in ICU patients (3, 8). Clearly, conventional diagnostic methods are no longer sufficient, much less efficient. We have to change how we approach the diagnosis of IPA in the ICU. The new findings (2) that BAL-GM is a valuable test for diagnosing IPA in apparently immunocompetent ICU patients set a new and practice-changing standard and one that comes without the requirement for additional procedures or novel technologies. All that is needed is to submit a sample for GM testing from fluid obtained during BAL, a commonly performed diagnostic procedure for VAP (1). In this study, all but two patients died, questioning the relevance of BAL-GM for optimal therapy of Aspergillus-induced VAP. This investigation, however, was designed to evaluate the diagnostic role of BAL-GM and clinicians were unaware of patient results. Importantly, the authors succeeded in addressing, for IPA, three major principles that underlie the optimal management of VAP in general (1): recognition of the variable microbial etiology among different ICU populations, accurate diagnosis to avoid antibiotic overuse, and early diagnosis with potential for prompt therapy to prevent mortality. Despite these important findings, several questions remain. Are the relatively high incidence of IPA and the good diagnostic yield of BAL-GM generalizable to other ICU settings? Can BAL-GM distinguish IPA from Aspergillus tracheobronchitis? Finally, can we improve serodiagnosis by more frequent sampling, test optimization, and/or by combining GM with other serum markers of aspergillosis (β-D-glucan, polymerase chain reaction, and Aspergillus antibodies) (8, 9)? If we were able to optimize the diagnostic performance of serum testing, we could have an even more positive impact on aspergillosis outcome. Indeed, the repeatability of serum tests offers advantages over BAL, including earlier, easier, and more definitive diagnosis; better distinction between airway colonization and infection; prompt application of preemptive therapy; and close monitoring of response (9–11). These features will become even more valuable as the population of apparently immunocompetent hosts at risk for IPA expands even further (12, 13). These and other questions require investigation in multicenter studies, which can now build on the groundbreaking work of Meersseman and colleagues. Only then can we reach the ultimate goal of improving patient outcome. FOOTNOTES Conflict of Interest Statement: E.J.A. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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