mercredi 5 février 2020 

14h10 - 15h10


 
Forum 6

Infectiologie : infections respiratoires

MODÉRATEUR(S) :  Charles-Edouard LUYT (Paris), Jean-François TIMSIT (Paris)  
  

Innate T cells during severe pneumonia and Acute Respiratory Distress Syndrome

Orateur(s) :   Youenn JOUAN (Tours) 

Auteur(s) :  Chloé BOISSEAU (Tours)   Antoine GUILLON (Tours)   Yonatan PEREZ (Tours)   Pierre-François DEQUIN (Tours)   Mustapha SI-TAHAR (Tours)   Christophe PAGET (Tours)  

14h10 - 14h18
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Innate T cells during severe pneumonia and Acute Respiratory Distress Syndrome

Introduction / Rationale :
Severe pneumonia can culminate in acute respiratory distress syndrome (ARDS). An uncontrolled inflammatory response is a key feature favoring transition towards ARDS. However, the underlying mechanisms remain poorly understood. In this context, the contribution of “innate T cells” (ITC) -a family of non-peptide reactive T cells comprising NKT cells, Mucosal Associated Invariant T (MAIT) cells and γδT cells- has never been explored. ITC have emerged as key players in orchestration of the host response during infections and inflammation processes. For these reasons, these cells are already seen as potential therapeutic targets in other medical fields (especially oncology). Here, we hypothesized that a tight regulation of their functions could be paramount to control the inflammatory response and to prevent ARDS development.

Méthodes / Patients and Methods :
To explore this, we combined a murine model of influenza A virus (IAV) infection mimicking ARDS symptoms and a clinical study recruiting patients admitted in ICU for severe pneumonia. Using flow-cytometry approaches, we investigated (1) the abundance and dynamics of ITC in various compartments, (2) their pattern of activation/regulation markers (respectively CD69 and PD-1) and (3) their cytokine production.

Résultats / Results :
During experimental IAV pneumonia, ITC were transiently recruited into the airways. Unlike γδT and NKT, MAIT cells phenotype was largely changed, displaying a progressive CD69 overexpression and increased IL-17A production. During the resolution phase, up to 90% of pulmonary MAITs expressed PD-1 (versus <10% in controls), which can suggest emergence of regulatory functions. Last, using gene-targeted mice, we suggested that MAIT cells confer a protective effect during pneumonia.

In the ongoing clinical study, the proportion of circulating MAIT cells in patients was markedly decreased compared to controls (1.0±1.0% versus 5.7±2.8% of T cells), but not for NKT or γδT cells. Notably, some patients with severe ARDS presented detectable levels of MAITs in their respiratory fluids. In addition, circulating MAIT cells in patients overexpressed CD69 and PD-1 (56.5% and 55% respectively), but with a reduced proportion able to produce IL-17 and IFNγ, compared to healthy controls. Lastly, proportion of activated (CD69+) MAIT cells significantly decreased with clinical improvement.

Discussion / Discussion :


Conclusion / Conclusion :
This translational approach combining in-vivo animal experiments and clinical samples with ex-vivo experiments indicates a preferential modulation in MAIT cells functions during severe pneumonia. These data justify an in-depth analysis of MAIT cells activation mechanisms and functions in this context, in order to further explore a potential use as a disease-progression marker and -in a long term perspective- as a potential therapeutic target.
 

A dominant circulating PD-1 / 2B4 CD8+ T-cells pattern at day 1 correlates with mortality but not with secondary infections in septic patients admitted to the ICU

Orateur(s) :   Stanislas FAGUER (Toulouse) 

Auteur(s) :  Damien GUINAULT (Toulouse)   Marie-laure NICOLAU-TRAVERS (Toulouse)   Stein SILVA (Toulouse)   Arnaud DEL BELLO (Toulouse)   Olivier COINTAULT (Toulouse)   Edith HOURCASTAGNOU (Toulouse)   David ROUSSET (Toulouse)   Laurence LAVAYSSIERE (Toulouse)   Marie-béatrice NOGIER (Toulouse)   Arnaud MARI (Toulouse)   Nassim KAMAR (Toulouse)   François VERGEZ (Toulouse)  

14h18 - 14h26
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
A dominant circulating PD-1 / 2B4 CD8+ T-cells pattern at day 1 correlates with mortality but not with secondary infections in septic patients admitted to the ICU

Introduction / Rationale :
Immune paralysis following hyperinflammatory states increases the risk of secondary infections and death. Reversing T-cells exhaustion using recombinant IL7 or immune checkpoints inhibitors may improve the prognosis of patients with sepsis admitted to the ICU. However, there is an unmet need to better characterize the state of T-cells exhaustion in these patients, its reproducibility and its correlation with the outcomes before implementing immunotherapy in the therapeutic armamentarium against sepsis.

Méthodes / Patients and Methods :
Prospective observational cohort study performed in two tertiary-care ICUs in a university hospital. Peripheral blood mononuclear cells were collected at day 1 in 80 adult patients with sepsis admitted to the ICU. The level of CD4+ and CD8+ T-cells exhaustion was quantified using multi-color flux cytometry targeting the following exhaustion markers: PD-1, 2B4 and CD160. CD4+ regulatory T-cells (CD3+ CD4+ CD25hi CD127Lo cells) were also assessed.

Résultats / Results :
The 80 patients included in the study could be split in five clusters according to their dominant pattern of exhaustion markers on CD8+ T-cell (i.e. no markers, PD-1+, 2B4+, 2B4+ CD160+ and 2B4+ PD-1+) and independently of their underlying morbidities. No patients harbored a fully exhausted triple-positive pattern. By multivariate analysis, SAPS2 gravity score at day 1 (p=0.007), a dominant 2B4 and/or PD-1 CD8+ pattern (p=0.04) and lung sepsis (p=0.02) where associated with the risk of death at day 28, whereas hemoglobin level was associated with survival (p=0.04). No CD4+ or CD8+ exhaustion pattern independently predicted the risk of secondary infections. Neither the level of CD4+ regulatory T-cells nor the dominant CD4+ exhaustion pattern was associated with the outcomes.

Discussion / Discussion :


Conclusion / Conclusion :
CD8+ T-cells of individuals with sepsis may express one or two exhaustion markers at the admission to the ICU but fully exhausted phenotype is rare, suggesting an intermediate state of T-cell activation or differentiation. A dominant 2B4 and/or PD-1 CD8+ pattern at day 1 is independently associated with mortality.
 

Comparison of one-year outcome of severe community-acquired bacterial or viral pneumonia and pneumonia of unidentified etiology

Orateur(s) :   Frédéric SANGLA (Clermont-Ferrand) 

Auteur(s) :  Pierre-Emmanuel MARTI (Genève)   David LEGOUIS (Genève)   Amélie BREBION (Clermont-Ferrand)   Pierre SAINT-SARDOS (Clermont-Ferrand)   Alexandre LAUTRETTE (Clermont-Ferrand)   Mireille ADDA (Clermont-Ferrand)   Bruno PEREIRA (Clermont-Ferrand)   Bertrand SOUWEINE (Clermont-Ferrand)  

14h26 - 14h34
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Comparison of one-year outcome of severe community-acquired bacterial or viral pneumonia and pneumonia of unidentified etiology

Introduction / Rationale :
There is growing use of multiplex polymerase chain reaction (mPCR) for respiratory virus testing in
patients with community-acquired pneumonia (CAP). Data on one-year outcomes in patients with
severe CAP of bacterial, viral and unidentified etiology are scarce.

Méthodes / Patients and Methods :
A single-center retrospective study was performed in 123 intensive care unit (ICU) patients with known
one-year survival status who had undergone respiratory virus testing for CAP by mPCR. One year after
ICU admission, mortality rates and functional status were compared in patients with CAP of bacterial,
viral or unidentified etiology.

Résultats / Results :
There were 19 (15.4%) patients in the bacterial group, 37 (30.1%) in the viral group and 67 (54.5%)
with unidentified etiology. One-year mortality was 57.9% (n=11/19), 27% (n=10/37) and 28.4%
(n=19/67), respectively (p=0.046). In multivariate analysis, one-year mortality was higher in the
bacterial group than in the viral group (HR 2.92, 95%CI 1.71-7.28, p=0.02), had a trend to be higher in
the bacterial group compared to the unidentified etiology group (HR 2.07, 95%CI 0.96-4.45, p=0.06)
and was not different between the viral and unidentified etiology groups (HR 0.71, 95%CI 0.30-1.65,
p=0.43). Severe dyspnea (mMRC score = 4 or death), major adverse respiratory events (new homecare
ventilatory support or death) and severe autonomy deficiencies (ADL Katz score ≤ 2 or death)
were observed in 52/104 (50.0%), 65/104 (62.5%) and 47/104 (45.2%) patients, respectively, with no
difference between groups.

Discussion / Discussion :


Conclusion / Conclusion :
CAP of bacterial origin was associated with a poorer prognosis than viral or unidentified etiology.
Impaired functional status was observed in a substantial proportion at one-year, irrespective of the
causative microorganisms involved.
 

Interest of UNYVERO multiplex PCR (CURETIS) for BAL rapid microbiologic and antibiotic susceptibility documentations in immunocompromised patients under antibiotic therapy

Orateur(s) :   Jean-Luc BAUDEL (Paris) 

Auteur(s) :  Jacques TANKOVIC (Paris)   Redouane DAHOUMANE (Paris)   Salah GALLAH (Paris)   Laurent BENZERARA (Paris)   Jean-remy LAVILLEGRAND (Paris)   Razach ABDALLAH (Paris)   Geoffroy HARIRI (Paris)   Naike BIGE (Paris)   Hafid AIT-OUFELLA (Paris)   Nicolas VEZIRIS (Paris)   Eric MAURY (Paris)   Bertrand GUIDET (Paris)  

14h34 - 14h42
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Interest of UNYVERO multiplex PCR (CURETIS) for BAL rapid microbiologic and antibiotic susceptibility documentations in immunocompromised patients under antibiotic therapy

Introduction / Rationale :
Our aim was to evaluate the interest of the Unyvero rapid (4.5 hours) multiplex PCR assay (performed on BAL samples) for the management of immunocompromised patients already treated with antibiotics and diagnosed with pneumonia (according to clinical and radiological findings). We thus performed an observational study that compared the results (and the length of time to obtain them) of routine microbiological evaluation and Unyvero assay.

Méthodes / Patients and Methods :
From July 2018 to January 2019 and from April to August 2019, we examined BAL samples from immunocompromised patients (coming from hematology, oncology, hepatology, gastroenterology, internal medicine, and neurology units) diagnosed with pneumonia (based on clinical and radiological findings), and already receiving antibiotic treatment. The following data were collected : age, gender, SAPS2 score, lung CT scan (92%) or X-ray (8%) results, duration and content of prior antibiotic therapy, direct examination, culture, antibiogram and Unyvero results, secondary confirmation of pneumonia or not, possible changes in antibiotic therapy that could have been made after obtention of Unyvero results. Informed consent was obtained from all patients.

Résultats / Results :
40 BAL samples were analyzed in 38 immunocompromised patients (m/f ratio 2.17 , SAPS2 51,5 +/- 6.8) mostly with hematologic (76 %) or oncologic (13%) diseases. The patients received either corticosteroids (47 %), or chemotherapy (37 %), or immunotherapy (8 %). 40% of the patients were under mechanical ventilation, 15 % under Optiflow. 32% presented a shock, 22 % had aplasia or neutropenia, 24 % were allografted, 16 % were autografted. The duration of prior antibiotic therapy at the time of BAL were 9.3 +/- 5.6 days. Direct examination was positive in 22.5 % of the cases, culture (both above and under the classical threshold of 104 CFU/ml) in 60 %, Unyvero in 47.5 %. A retrospective analysis of all the cases confirmed the initial diagnosis of pneumonia in only 50 % of the cases. Compared to culture, the sensitivity of Unyvero was 81 %, its specificity 94 %. Unyvero could permit to rapidly deescalate antibiotic therapy in 42% of the cases and to rapidly stop it in 32 %.

Discussion / Discussion :


Conclusion / Conclusion :
The Unyvero assay on BAL samples is useful in this specific population for rapid obtention of microbiological results and also for confirmation of the negativity of cultures and thus permits a better management of antibiotic therapy, leading to a reduction of antibiotic resistance selection pressure in the ICU.
 

Do not underestimate RSV pneumonia among critically ill patients.

Orateur(s) :   Erwan BEGOT (Bordeaux) 

Auteur(s) :  Suzanne CHAMPION (Bordeaux)   Charline SAZIO (Bordeaux)   Benjamin CLOUZEAU (Bordeaux)   Alexandre BOYER (Bordeaux)   Hoang-Nam BUI (Bordeaux)   Marie-edith LAFON (Bordeaux)   Camille CICCONE (Bordeaux)   Julia DINA (Caen)   Didier GRUSON (Bordeaux)   Renaud PRÉVEL (Bordeaux)  

14h42 - 14h50
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Do not underestimate RSV pneumonia among critically ill patients.

Introduction / Rationale :
Respiratory syncitial virus (RSV) is a well-known cause of respiratory failure among neonates but its pathogenicity in adults is now emerging as a potential cause of viral pneumonia. Data are limited with conflicting results regarding RSV pneumonia severity in adults. Data are lacking about critically ill RSV patients’ characteristics and outcomes. The aim of this study is to compare RSV patients’ characteristics, care and outcomes to influenza patients’ ones.

Méthodes / Patients and Methods :
Patients diagnosed with RSV and influenza pneumonia admitted to our medical ICU were included. Data were retrospectively recorded. Quantitative data are expressed by median and interquartile range and compared by use of Mann-Whitney test. Qualitative data are expressed by number and percentages and compared by use of Fischer exact t-test. RSV strains were prospectively collected.

Résultats / Results :
Eighteen critically ill patients with RSV pneumonia and 95 with influenza pneumonia were included. RSV and influenza patients had the same characteristics at admission except for age (respectively 71yo [62 ; 81] vs 63yo [51 ; 70], p: 0.03). In particular, they had similar rates of underlying chronic pulmonary disease (respectively 10/18 (56%) vs 43/95 (45%), p : 0.45) or haematological malignancy (2/18 (12%) vs 9/95 (10%) , p : 1.00). They exhibited similar presentation with similar SAPSII scores (respectively 46 [38 ; 63] vs 53 [34 ; 74], p : 0.55), PaO2/FiO2 ratio (respectively 195 [145 ; 256] vs 157 [100 ; 226], p : 0.15) and acute respiratory distress syndrome rates (respectively 7/18 (39%) vs 47/95 (49%), p: 0.44). They received similar treatment as suggested by oro-tracheal intubation rates (respectively 6/18 (33%) vs 52/95 (54%), p : 0.12) and antibiotics prescription (respectively 16/18 (89%) vs 88/95 (93%), p : 0.63). RSV and influenza patients also had the same rates of bacterial co-infections (4/18 (22%) vs 28 (29%), p : 0.78). Invasive aspergillosis remained a rare event but also occurred among RSV patients (1/18 (6%) vs 3/95 (3%), p : 0.51). Acute coronary syndromes were as frequent in both groups (respectively 2/18 (12%) vs 9/95 (10%), p: 1.00). Day-28 mortality was similar between RSV and influenza patients (respectively 3/18 (19%) vs 23 (24%), p : 0.76). RSV strains typing is under progress.

Discussion / Discussion :


Conclusion / Conclusion :
Patients suffering from RSV pneumonia admitted to ICU have similar presentation, care and day-28 mortality than critically ill influenza patients. The severity of RSV pneumonia diagnosis should not be underestimated by intensivists.
 

Determinants of respiratory distress from seawater drowning: a prospective observational study from 7 intensive care units on the French Riviera.

Orateur(s) :   Alexandre ROBERT (Fréjus-Draguignan) 

Auteur(s) :  Denis DOYEN (Nice)   Pierre-marie BERTRAND (Cannes)   Michel KAIDOMAR (Fréjus-Draguignan)   Nicolas CLEMENT (Cannes)   Nicolas BELE (Fréjus-Draguignan)   Nihal MARTIS (Nice)   Hervé QUINTARD (Nice)   Hervé HYVERNAT (Nice)   Gilles BERNARDIN (Nice)   Jean DELLAMONICA (Nice)  

14h50 - 14h58
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Determinants of respiratory distress from seawater drowning: a prospective observational study from 7 intensive care units on the French Riviera.

Introduction / Rationale :
Respiratory distress from seawater drowning is commonly considered multifactorial. Etiologies are debatable and include heart failure, infection and acute respiratory distress syndrome (ARDS). Documented bacterial infections seems mostly related to the site of drowning. Data in this regard are scarce with prospective studies lacking. The objective of our study was to describe prospectively the characteristics and determinants of respiratory distress from Seawater Drowning.

Méthodes / Patients and Methods :
All patients admitted for seawater drowning to 7 intensive care units (ICU) on the French Riviera in the summers of 2017 and 2018 were prospectively included. Recorded data included clinical features on examination, personal history, chest X-rays, echocardiography and biological results obtained within the first 48 hours. A paired Student’s t-test was used to study statistical differences between quantitative variables on admission and during early evaluation (i.e. first 48 hours).

Résultats / Results :
Forty-eight patients were admitted to 5 centers of which 45 (94%) were diagnosed as having ARDS, 31 (65%) early pneumonia and 4 (8%) acute cardiogenic pulmonary edema.
Twenty-one (44%) respiratory samples were collected but bacterial culture was positive in only 5 cases. Multidrug-resistant bacteria were not observed, and amoxicillin-clavulanate as first-line treatment was effective in all cases. Echocardiography performed in 38 (75%) patients was normal and unable to identify specific patient profiles. The median Clinical Pulmonary Infection Score (CPIS) on admission was 6 (IQR, 5-7) and decreased rapidly and significantly (p <0.0001) within 24 hours to 3 (IQR, 2-3) (Figure 1).

Discussion / Discussion :


Conclusion / Conclusion :
Data from this multicenter cohort suggest that respiratory distress following seawater drowning can mimic bacterial pneumonia during the first 24 hours with subsequent rapid clinical improvement in patients admitted to the ICU. Probabilistic antibacterial therapy should therefore be limited to the most severe patients. Isolate ARDS is often the only etiology found and is resolutive within 24 hours. This prospective cohort is the largest of its kind and gives a better insight into the limited impact of cardiogenic and infectious processes on sea drowning-related respiratory distress.
 

Impact of Extra-Corporeal Membrane Oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study

Orateur(s) :   Pierre FILLATRE (Saint-Brieuc) 

Auteur(s) :  Florian LEMAITRE (Rennes)   Nicolas NESSELER (Rennes)   Matthieu SCHMIDT (Paris)   Sebastien BESSET (Paris)   Yoann LAUNEY (Rennes)   Adel MAAMAR (Rennes)   Pierre DAUFRESNE (Rennes)   Erwan FLECHER (Rennes)   Yves LE TULZO (Rennes)   Jean-Marc TADIÉ (Rennes)   Pierre TATTEVIN (Rennes)  

14h58 - 15h06
Durée de la présentation : 5 min
Durée de la discussion : 3 min


Abstract : 
Impact of Extra-Corporeal Membrane Oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study

Introduction / Rationale :
Patients treated with "ExtraCorporeal Membrane Oxygenation" (ECMO) are at a higher risk of developing nosocomial infections and they are consequently often treated with beta-lactams. French guidelines recommend obtaining beta-lactam trough concentrations above four times the minimal inhibitory concentration (MIC) of the causative bacteria. The ECMO device may alter the pharmacokinetics of these medications, which may result in underexposure to beta-lactam antibiotics.

Méthodes / Patients and Methods :
This observational, prospective, multicenter, case-control study was performed in the intensive care units of two tertiary care hospitals in France. ECMO Patients with sepsis treated with piperacillin-tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin was described based on a population pharmacokinetic model, allowing to calculate the time spent above 4 x the MIC breakpoint for Pseudomonas aeruginosa susceptibility after the first dose and at steady state between two piperacillin infusions.

Résultats / Results :
Forty-two patients were included. The median age was 60 years [49-66], the SOFA score was 11 [9-14], and median creatinine clearance was 47mL/min [5-95]. There was no significant difference in the time above 4 x MIC in patients treated with ECMO and controls during the first administration (p=0.184) and at steady state (p=0.309). There was no significant difference between the trough at steady state (p=0.535), with 18/42 patients (43%) exhibiting concentrations of piperacillin lower than 4 x MIC. ECMO support was not associated with a steady state trough concentration below 4 x MIC (OR = 0.5 [0.1 – 2.1], p=0.378). The only variable independently associated with this risk was a creatinine clearance ≥ 40 mL/min,(OR =4.3 [1.1-17.7], p=0.043).

Discussion / Discussion :


Conclusion / Conclusion :
ECMO support has no significant impact on piperacillin exposure. Intensive care unit patients with sepsis are, however, frequently underexposed with piperacillin, which suggest that therapeutic drug monitoring should be strongly recommended for severe infections.