Diagnostic accuracy of inflammatory biomarkers in bronchoalveolar lavage from patients with ventilator-associated pneumonia

BackgroundVentilator associated pneumonia (VAP) is a common complication in intensive care patients. The clinical diagnosis is difficult and a definite microbiological diagnosis based on quantitative culture of bronchoalveolar lavage (BAL) fluid is mandatory. Many biological markers have been studied in an effort to improve the rapidity and performance of current diagnostic procedures in VAP. So, this study was done with the objective to determine the discriminative power of single or combining multiple biomarkers in bronchoalveolar lavage including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase plasminogen activator receptor (suPAR), and macrophage migration inhibitory factor (MIF) for the diagnosis of bacterial VAP among patients who were receiving mechanical ventilation.Patients and methodsThis study was conducted in the intensive care units of Chest, Internal Medicine and Anesthesia Departments, Zagazig University Hospitals, Egypt, between January and December 2012, 66 adult patients were included who were receiving mechanical ventilation and eligible for BAL for suspected VAP. The microbiology was assessed with quantitative cultures of BAL obtained within the first 6 h after the development of a new pulmonary infiltrate on chest radiography. All patients were divided into: Group 1, “definite VAP” with positive quantitative culture results, Group 2, “indeterminate VAP” with negative BAL culture and received new antibiotics at least 24 h prior to BAL, and Group 3, “definite absence of VAP,” with negative BAL culture and not receiving antibiotics at the time of BAL.MeasurementsProcalcitonin was measured using an ultrasensitive chemiluminometric assay. CRP was measured using an enzyme immunoassay. Measurements of sTREM-1, suPAR, and MIF were performed using a Luminex multiplex assay. Two composite markers were constructed; one including a linear combination of the three best performing markers and another including all six markers and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers.ResultsOf the total 66 enrolled patients receiving mechanical ventilation and undergoing BAL for suspected pneumonia, 20 patients (30.3%) met definite microbiologic criteria for group 1, 28 patients (42.4%) with indeterminate VAP in group 2, and 18 patients (27.2%) with definite absent VAP in group 3. The mean concentrations of all studied biomarkers were not statistically significant when their levels in BAL samples from patients with definite VAP were compared with either from definite absence of VAP or from indeterminate VAP (all p > 0.05). The AUCs for discrimination between infection of bacterial origin and no infection were 0.83 (95% CI 0.79–0.88) for CRP, 0.77 (95% CI 0.69–0.79) for PCT, 0.72 (95% CI 0.67–0.77) for neutrophils, 0.60 (95% CI 0.83–0.69) for MIF, 0.68 (95% CI 0.56–0.67) for sTREM-1 and 0.51 (95% CI 0.48–0.59) for suPAR, 0.86 (0.79–0.89|) for the composite three-marker test (CRP, PCT, and neutrophils), and 0.90 (0.83–0.96) for the composite six-marker test. The six-marker test performed significantly better than all of the single markers (P < 0.05 for the three-marker test and CRP and P < 0.001 for the five remaining markers).ConclusionsSingle measurements of sTREM-1, suPAR or MIF concentrations in the BAL fluid of mechanically-ventilated patients with new or progressive infiltrates do not enhance identification of VAP. However, combining results from several inflammatory markers may significantly improve the ability to differentiate bacterial from nonbacterial infections. Further studies are needed to fully determine the diagnostic accuracy of these and other biomarkers.