Hospital-acquired pneumonia in ICU : characterization according to the existence and the duration of mechanical ventilation

Les infections nosocomiales représentent la première cause de mortalité et le premier poste de prescription d’antibiothérapies. Les pneumopathies nosocomiales représentent la première cause de morbi-mortalité en réanimation. Dans un contexte de ressources antibiotiques limitées et une augmentation de l’incidence des germes résistants, nous avons étudié:1°) Les facteurs de risque de pneumopathies acquises sous ventilation mécanique (PAVM) en tenant compte de la durée de la ventilation mécanique2°) La différence entre les pneumopathies associées aux soins en réanimation chez les patients non ventilés et les pneumonies acquises sous ventilation mécanique en terme d’étiologie et de conséquences pronostiques.3°) L’impact de l’adéquation de l’antibiothérapie initiale et les facteurs de risque d’avoir un traitement inadéquat du fait de la résistance bactérienne dans les PAVM à germes gram négatifs.Nos résultats montrent que : Les pneumonies acquises en réanimation en dehors de la ventilation mécanique invasive (ICU-HAP) et les PAVM sont dues aux mêmes germes avec un risque de décès plus important chez les ICU-HAP. Les PAVM précoces et tardives sont associées à des facteurs de risques différents pouvant justifier de politiques de préventions différentes. L’antibiothérapie préalable et la colonisation préalable à des bactéries multi résistantes expliquent la survenue de PAVM à Gram négatifs résistants. La durée de ventilation invasive avant la survenue de la pneumopathie n’est pas un facteur de risque indépendant de survenue de PAVM à gram négatifs résistants. Un pourcentage d’infection ou de colonisation à bacille gram négatif (BGN) résistant supérieur à 10% dans le centre est associé à la survenue d’une PAVM à gram négatif résistant, indépendamment des facteurs individuels. Les PAVM à S. maltophilia surviennent très tardivement, sont très largement associées à une consommation d’antibiotiques élevée, en particulier les pénèmes. Elles sont plus souvent associées à une antibiothérapie initiale inadéquate.Notre travail confirme la nécessité d’un effort particulier afin d’optimiser le diagnostic et l’adéquation précoce des antibiothérapies, en particulier pour les pneumonies acquises en dehors de la ventilation mécanique et les PAVM à BGN potentiellement résistants aux antibiotiques.Healthcare-associated infections are the leading cause of death and the first prescription of antibiotics. Healthcare-associated pneumonia represents the first cause of morbidity mortality in ICU. In the context of limited antibiotic resources and an increase in the incidence of resistant germs, we studied:1) Risk factors for ventilator acquired pneumonia (VAP) taking into account the duration of mechanical ventilation (MV).2) If there is a difference between nonventilated and mechanically ventilated pneumonia in terms of etiology and prognostic?3) What is the impact of the adequacy of the initial antibiotic treatment, and what are the risk factors for inadequate treatment in gram-negative resistant VAP?Our results show that: Pneumonia acquired by no ventilated patient in the ICU (ICU-HAP) and VAP are due to the same germs with a higher risk of death in ICU-HAP. Early and late VAP are associated with different risk factors that may need different prevention policies. Previous-antibiotic therapy and prior-colonization with multiresistant bacteria explain the occurrence of resistant Gram Negative VAP. Duration of MV before the onset of pneumonia is no longer an independent risk factor for the occurrence of resistant gram-negative VAP. A percentage of infection or colonization with resistant BGN upper to 10% in the centre is associated with the occurrence of a gram-negative, resistant PAVM, regardless of individual risk factors. S. maltophilia VAP occurs belatedly and are very widely associated with high antibiotic consumption, especially penems. They are more often associated with inadequate initial antibiotic therapy.Our work confirms the need for further research to optimize the diagnosis and early adequacy of antibiotics, in particular in ICU-HAP and VAP caused by potentially antibiotic-resistant BGN

Ventilator-associated pneumonia due to Stenotrophomonas maltophilia: Risk factors and outcome

International audienceBackground: Stenotrophomonas maltophilia (SM) is increasingly identified in intensive care unit (ICU). This study aim to identify risk factors for SM ventilator-associated pneumonia (VAP) and whether it affects ICU mortality METHODS: Two nested matched case-control studies were performed based in OUTCOMEREA database. The first episodes of SM-VAP patients were matched with two different control groups: VAP due to other micro-organisms (VAP-other) and Pseudomonas aeruginosa VAP (Pyo-VAP). Matching criteria were the hospital, the SAPS II, and the previous duration of mechanical ventilation (MV).Results: Of the 102 SM-VAP patients (6.2% of all VAP patients), 92 were matched with 375 controls for the SM-VAP/other-VAP matching and 84 with 237 controls for the SM-VAP/Pyo-VAP matching. SM-VAP risk factors were an exposition to ureido/carboxypenicillin or carbapenem during the week before VAP, and respiratory and coagulation components of SOFA score upper to 2 before VAP. SM-VAP received early adequate therapy in 70 cases (68.6%). Risk factors for Day-30 were age (OR = 1.03; p 2 before VAP. Mortality risk factors of SM-VAP were age and chronic heart failure. Adequate treatment did not improve SM-VAP prognosis

Respective impact of implementation of prevention strategies, colonization with multiresistant bacteria and antimicrobial use on the risk of early- and late-onset VAP: An analysis of the OUTCOMEREA network.

The impact of prevention strategies and risk factors for early-onset (EOP) versus late-onset (LOP) ventilator-associated pneumonia (VAP) are still debated.To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies.7,784 patients with mechanical ventilation (MV) for at least 48 hours were selected into the multicenter prospective OUTCOMEREA database (1997-2016). VAP occurring between the 3rd and 6th day of MV defined EOP, while those occurring after defined LOPs. We used a Fine and Gray subdistribution model to take the successful extubation into account as a competing event.Overall, 1,234 included patients developed VAP (EOP: 445 (36%); LOP: 789 (64%)). Male gender was a risk factor for both EOP and LOP. Factors specifically associated with EOP were admission for respiratory distress, previous colonization with multidrug-resistant Pseudomonas aeruginosa, chest tube and enteral feeding within the first 2 days of MV. Antimicrobials administrated within the first 2 days of MV were all protective of EOP. ICU admission for COPD exacerbation or pneumonia were early risk factors for LOP, while imidazole and vancomycin use within the first 2 days of MV were protective factors. Late risk factors (between the 3rd and the 6th day of MV) were the intra-hospital transport, PAO2-FIO2<200 mmHg, vasopressor use, and known colonization with methicillin-resistant Staphylococcus aureus. Among the antimicrobials administered between the 3rd and the 6th day, fluoroquinolones were the solely protective one.Contrarily to LOP, the risk of EOP decreased across the study time periods, concomitantly with an increase in the compliance with bundle of prevention measures.VAP risk factors are mostly different according to the pneumonia time of onset, which should lead to differentiated prevention strategies

Flowchart.

<p>Flowchart.</p

Characteristics of study population at the ICU admission.

<p>Characteristics of study population at the ICU admission.</p

Characteristics of patients at risk for early and late onset pneumonia during their stay in ICU.

<p>Characteristics of patients at risk for early and late onset pneumonia during their stay in ICU.</p

Causative pathogens according to the type of ventilator-associated pneumonia, EOP or LOP.

<p>Causative pathogens according to the type of ventilator-associated pneumonia, EOP or LOP.</p

Summary of risk factors of early- and late-onset pneumonia.

<p>Summary of risk factors of early- and late-onset pneumonia.</p

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old