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ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p

Abstract Background To propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid therapy for the prevention of HAP. Methods This was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisoltotal&free, as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28. Results Of the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisoltotal&free and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisoltotal/CRP ratio upon admission was 2.30 [1.25–3.91] in patients without HAP and 3.36 [1.74–5.09] in patients with HAP (p = 0.021). In multivariate analysis, a cortisoltotal/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% [1.34–4.64] p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% [0.34–1.00], p = 0.005) in patients with a cortisoltotal/CRP ratio > 3, and 0.89 (CI95% [0.49–1.64], p = 0.85) in patients with a ratio 3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP.

Dendritic cells (DCs) are bone marrow derived cells which continuously seed in peripheral tissue. During infection, DCs play an essential interface between innate and adaptive immunity. Pneumonia is a lung inflammation triggered by pathogens and is characterized by excessive release of inflammatory cytokines that activate innate and acquired immunity. Pneumonia induces a rapid and protracted state of susceptibility to secondary infection, a state so-called sepsis-induced immunosuppression. In this review, we focus on the role of DCs in the development of this state of immunosuppression. Early during inflammation, activated DCs are characterized by decreased capacity of antigen (cross)- presentation of newly encountered antigens and decreased production of immunogenic cytokines, and sepsis-induced immunosuppression is mainly explained by a depletion of immature DCs which had all become mature. At a later stage, newly formed respiratory immature DCs are locally programmed by an immunological scare left-over by inflammation to induce tolerance. Tolerogenic Blimp1+ DCs produce suppressive cytokines such as tumor growth factor-B and participate to the maintenance of a local tolerogenic environment notably characterized by accumulation of Treg cells. In mice, the restoration of the immunogenic functions of DCs restores the mucosal immune response to pathogens. In humans, the modulation of inflammation by glucocorticoid during sepsis or trauma preserves DC immunogenic functions and is associated with resistance to secondary pneumonia. Finally, we propose that the alterations of DCs during and after inflammation can be used as biomarkers of susceptibility to secondary pneumonia and are promising therapeutic targets to enhance outcomes of patients with secondary pneumonia.