Next Steps for Confirming Bronchoalveolar Lavage Amlyase as an Useful Biomarker for Ventilator-Associated Pneumonia*

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Ventilator-associated pneumonia (VAP) is a common infectious complication in the ICU setting, occurring in 10% of mechanically ventilated patients (1, 2). It is associated with prolonged duration of mechanical ventilation and hospitalization, increased costs, and has an attributable mortality estimated at 13% in a recent meta-analysis (3, 4).
When VAP is suspected, broad-spectrum antibiotics are started, and cultures are sent for confirmation. If nothing grows on culture, then antibiotics are typically stopped at 48–72 hours. Ruling out VAP earlier, however, could avoid unnecessary antibiotic use (5)—which is increasingly recognized as an important means to preventing antimicrobial resistance. Alpha-amylase levels may help rule in or rule out the diagnosis earlier.
Alpha-amylase originates in the gut and oropharynx but can end up in the lung if a patient aspirates gastric or oropharyngeal contents. Aspiration is common in critically ill patients and is strongly associated with developing VAP (6). Alpha-amylase levels in the lung can serve as a marker of aspiration (7).
In this issue of Critical Care Medicine, Samanta et al (8) performed a prospective observational cohort study of patients with clinically suspected VAP. All patients underwent mini bronchoalveolar lavage (BAL), and lavage fluid was sent for both alpha-amylase level and quantitative culture. The primary hypothesis was that patients with culture-confirmed VAP would have higher levels of alpha-amylase.
The study enrolled 151 patients from a single tertiary academic medical center, who had a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18. Mini BALs were completed on all patients within 72 hours of intubation, and respiratory culture confirmed the diagnosis of VAP in 65%. As hypothesized, alpha-amylase levels were higher in those patients ultimately confirmed to have VAP. 163 U/L was identified as the alpha-amylase cutoff that best discriminated between patients with and without VAP (as defined by positive BAL culture) and yielded a sensitivity of 73% and specificity of 69% for VAP diagnosis.
This study (8) is the first prospective evaluation of alpha-amylase as a diagnostic biomarker in patients with clinically suspected VAP. Prior studies have demonstrated that alpha-amylase can be measured in tracheal aspirates of patients with tracheostomies and laryngectomies (9, 10); that alpha-amylase can be used to quantify the magnitude of microaspiration in both pediatric (11) and mechanically ventilated adult patients (12, 13); and, in retrospective data, that patients with VAP have higher levels of alpha-amylase in BAL fluid (14). This study (8) extends prior research to show that among prospectively identified patients at high risk for VAP, alpha-amylase levels are strongly associated with VAP diagnosis based on positive culture results. This suggests that alpha-amylase may be a useful biomarker for early VAP diagnosis.
Before alpha-amylase measurement can be recommended for routine practice, however, additional work is needed. The study by Samanta et al (8) included 151 patients from a single center. Mortality was higher than other studies of VAP with similar APACHE II scores (15, 16). Ninety-five percent of the pathogens identified were gram-negative, whereas prior epidemiologic studies suggest that gram-positive organisms typically account for at least 30% of culture isolates (1). In addition, all patients had early-onset VAP, as mini BAL samples were collected within 72 hours of intubation. Future studies are needed to confirm these results extend to other patient populations, for example, in patients with gram-positive or late-onset VAP.
In addition to confirming external generalizability, it is also important to consider the best way for BAL alpha-amylase to assist clinical decision-making. 163 U/L was identified as the cut point that optimized both sensitivity and specificity.
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