Publications by authors named "Philippe Montravers"

191 Publications

Blood transfusion of the donor is associated with stage 3 primary graft dysfunction after lung transplantation.

Clin Transplant 2021 Jun 26:e14407. Epub 2021 Jun 26.

APHP, CHU Bichat-Claude Bernard, DMU PARABOL, Paris, France.

Background: The first aim of this study was to assess the association between stage 3 PGD and pre-donation blood transfusion of the donor. The secondary objectives were to assess the epidemiology of donor transfusion and the outcome of LT recipients according to donor transfusion status and massive donor transfusion status.

Methods: This was an observational, prospective, single-center study. The results are expressed as absolute numbers, percentages, medians, and interquartile ranges. Statistical analyses were performed using Chi squared, Fischer's exact tests, and Mann-Whitney U tests (P < .05 was considered significant). A multivariate analysis was performed.

Results: Between January 2016 and February 2019, 147 patients were included in the analysis. PGD was observed in 79 (54%) patients, 45 (31%) of whom had stage 3 PGD. Pre-donation blood transfusion was administered in 48 (33%) donors (median of 3[1-9] packed red cells (PRCs)). On multivariate analysis, stage 3 PGD was significantly associated with donor blood transfusion (OR 2.69, IC (1.14-6.38), P = .024). Mortality at days 28 and 90 was not significantly different according to the pre-donation transfusion status of the donor.

Conclusion: Pre-donation blood transfusion is associated with stage 3 PGD occurrence after LT. Transfusion data of the donor should be included in donor lung assessment.
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http://dx.doi.org/10.1111/ctr.14407DOI Listing
June 2021

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units.

Drugs 2021 Jun 26;81(9):1065-1078. Epub 2021 May 26.

UFR Denis Diderot, INSERM UMR 1152, ANR-10-LABX-17, Department of Anaesthesiology and Critical Care Medicine, DMU PARABOL, CHU Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France.

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.
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http://dx.doi.org/10.1007/s40265-021-01534-wDOI Listing
June 2021

Clinical reasoning in anaphylactic shock: addressing the challenges faced by anaesthesiologists in real time: A clinical review and management algorithms.

Eur J Anaesthesiol 2021 May 10. Epub 2021 May 10.

From the Anaesthesiology and Critical Care Medicine Department, DMU PARABOL, Bichat Hospital, AP-HP (AGC, EK, PM, DL), Antibody in Therapy and Pathology, Pasteur Institute, UMR 1222 INSERM, Paris, France (AGC), Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (AGC), Pulmonology Department, Bichat Hospital, AP-HP, Paris University (CN), INSERM UMR 1152, Paris University, DHU FIRE, Paris (CN, PM), Anaesthesiology and Critical Care Medicine Department, Maison Blanche Hospital, Centre Hospitalier Universitaire de Reims, Reims (JM-M), Anaesthesiology and Critical Care Medicine Department, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg (CT, PM-M), Paris University (PM, DL), EA 3072, Institut de Physiologie, FMTS, Faculté de Médecine de Strasbourg, Université de Strasbourg, Strasbourg (PM-M) and INSERM1148, Paris, France (DL).

Acute hypersensitivity reactions to drugs occur infrequently during anaesthesia and the peri-operative period. When clinical presentation includes the classical triad, erythema, cardiovascular abnormalities and increased airway pressure, the diagnosis is evident and the challenge is to prescribe a therapeutic regimen according to guidelines and to manage refractory signs in a timely manner. In many situations, however, the initial clinical signs are isolated, such as increased airway pressure or arterial hypotension. Rendering a differential diagnosis with causes and mechanisms other than acute hypersensitivity reactions (AHRs) is difficult, delaying treatment with possible worsening of the clinical signs, and even death, in previously healthy individuals. In these difficult diagnostic situations, clinical reasoning is mandatory, and guidelines do not explicitly explain the elements on which clinical reasoning can be built. In this article, based on clinical evidence whenever available, experimental data and pathophysiology, we propose algorithms that have been evaluated by experts. The goal of these algorithms is to provide explicit elements on which the differential diagnosis of AHRs can be made, accelerating the implementation of adequate therapy.
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http://dx.doi.org/10.1097/EJA.0000000000001536DOI Listing
May 2021

Major adverse cardiovascular events and anaesthetic management in pregnant women with cardiac disease: a retrospective, single-centre study.

Br J Anaesth 2021 07 7;127(1):e8-e10. Epub 2021 May 7.

Département d'Anesthésie-Réanimation, DMU PARABOL, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.

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http://dx.doi.org/10.1016/j.bja.2021.03.032DOI Listing
July 2021

Effectiveness of anaesthesia ventilator use for mechanical ventilation in critically ill patients during the COVID-19 pandemic.

Br J Anaesth 2021 07 12;127(1):e35-e37. Epub 2021 Apr 12.

Anaesthesiology and Critical Care Medicine Department, DMU PARABOL, Bichat Hospital, AP-HP, Paris, France; Université de Paris, FHU PROMICE, Paris, France; INSERM UMR 1152, ANR-10-LABX-17, Paris, France.

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http://dx.doi.org/10.1016/j.bja.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041185PMC
July 2021

Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France.

PLoS One 2021 29;16(4):e0250728. Epub 2021 Apr 29.

Université de Paris, INSERM, IAME, Paris, France.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084132PMC
May 2021

COVID-19 vaccines: A race against time.

Anaesth Crit Care Pain Med 2021 04 24;40(2):100848. Epub 2021 Mar 24.

Department of Anaesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; INSERM UMR1152, ANR-10-LABX-17, Paris, France.

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http://dx.doi.org/10.1016/j.accpm.2021.100848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987582PMC
April 2021

Dynamic Changes in Microbial Composition During Necrotizing Soft-Tissue Infections in ICU Patients.

Front Med (Lausanne) 2020 4;7:609497. Epub 2021 Mar 4.

Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France.

Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries. This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses. Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50-68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1-7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including , staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR ( < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms ( = 0.79) and MDR bacteria ( = 1.0) or the 1-year survival rate. The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.
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http://dx.doi.org/10.3389/fmed.2020.609497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969649PMC
March 2021

Impact of rapid multiplex PCR on management of antibiotic therapy in COVID-19-positive patients hospitalized in intensive care unit.

Eur J Clin Microbiol Infect Dis 2021 Mar 17. Epub 2021 Mar 17.

Université de Paris, INSERM, IAME, F-75006, Paris, France.

Because the diagnosis of co/superinfection in COVID-19 patients is challenging, empirical antibiotic therapy is frequently initiated until microbiological analysis results. We evaluated the performance and the impact of the BioFire® FilmArray® Pneumonia plus Panel on 112 respiratory samples from 67 COVID-19 ICU patients suspected of co/superinfections. Globally, the sensitivity and specificity of the test were 89.3% and 99.1%, respectively. Positive tests led to antibiotic initiation or adaptation in 15% of episodes and de-escalation in 4%. When negative, 28% of episodes remained antibiotic-free (14% no initiation, 14% withdrawal). Rapid multiplex PCRs can help to improve antibiotic stewardship by administering appropriate antibiotics earlier and avoiding unnecessary prescriptions.
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http://dx.doi.org/10.1007/s10096-021-04213-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968559PMC
March 2021

Epidemiology, clinical relevance and prognosis of staphylococci in hospital-acquired postoperative intra-abdominal infections: an observational study in intensive care unit.

Sci Rep 2021 Mar 15;11(1):5884. Epub 2021 Mar 15.

Hôpitaux de Paris, Department of Anesthesiology and Critical Care Medicine, DMU PARABOL Bichat-Claude Bernard Hospital, 46 rue Henri Huchard, 75018, Paris, France.

The pathogenic role of staphylococci in hospital-acquired postoperative intra-abdominal infections (HAIs) has never been evaluated. In a tertiary care university hospital, we assessed the clinical characteristics and outcomes of patients admitted to the intensive care unit for HAIs according to the presence of staphylococci (S-HAI) or their absence (nS-HAI) in peritoneal cultures. Patients with S-HAIs were compared to nS-HAIs patients. Overall, 380 patients were analyzed, including 87 (23%) S-HAI patients [29 Staphylococcus aureus (Sa-HAIs) and 58 coagulase-negative staphylococci (CoNS-HAIs)]. The clinical characteristics did not differ between the S-HAI and nS-HAI patients. Adequacy of empirical anti-infective therapy was achieved less frequently in the staphylococci group (54 vs 72%, respectively, p < 0.01). The 90-day (primary endpoint) and one-year mortality rates did not differ between these groups. The S-HAI patients had decreased rates of postoperative complication (p < 0.05). The adjusted analysis of the clinical outcomes reported a decreased frequency of surgical complications in the staphylococci group (OR 0.43, 95% CI [0.20-0.93], p = 0.03). While the trends toward decreased morbidity criteria were observed in S-HAI patients, the clinical outcomes were not different between the CoNS-HAI and Sa-HAI patients. In summary, our data are not substantial enough to conclude that staphylococci exhibit no pathogenicity in HAIs.
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http://dx.doi.org/10.1038/s41598-021-85443-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960962PMC
March 2021

Can we learn from others? The Swedish intensive care unit database for COVID-19 cases.

Eur J Anaesthesiol 2021 04;38(4):331-332

From the Département d'Anesthésie-Réanimation, CHU Bichat-Claude Bernard, DMU PARABOL, HUPNVS, APHP (PM, AG-C), Université de Paris (PM), INSERM UMR 1152, ANR-10-LABX-17, Université de Paris (PM), Institut Pasteur, Inserm UMR 1222, Paris, France (AG-C), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Biostatistics Research Branch, Division of Clinical Research, Bethesda, Maryland, USA (AG-C).

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http://dx.doi.org/10.1097/EJA.0000000000001449DOI Listing
April 2021

Impact of treating iron deficiency, diagnosed according to hepcidin quantification, on outcomes after a prolonged ICU stay compared to standard care: a multicenter, randomized, single-blinded trial.

Crit Care 2021 02 15;25(1):62. Epub 2021 Feb 15.

Laboratoire de Biochimie Protéomique Clinique Et IRMB INSERM, CHU de Montpellier, Université de Montpellier, Montpellier, France.

Background: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes.

Methods: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 μg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival.

Results: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 μg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04).

Conclusion: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically ill patients about to be discharged after a prolonged stay.

Trial Registration: www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).
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http://dx.doi.org/10.1186/s13054-020-03430-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885380PMC
February 2021

Altered high-density lipoprotein composition and functions during severe COVID-19.

Sci Rep 2021 01 27;11(1):2291. Epub 2021 Jan 27.

INSERM, UMR 1188 Diabète atherothombose Réunion Océan Indien (DéTROI), Université de La Réunion, Saint-Denis de La Réunion, France.

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
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http://dx.doi.org/10.1038/s41598-021-81638-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841145PMC
January 2021

Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study.

Ann Intensive Care 2021 Jan 19;11(1):11. Epub 2021 Jan 19.

Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, DMU PARABOL, Bichat-Claude Bernard Hospital, Paris, France.

Background: High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome.

Methods: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient's hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed.

Results: A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04-1.57) mmol/l; day 1 HDL-C = 0.44 (0.29-0.70) mmol/l; day 3 HDL-C = 0.30 (0.25-0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42-0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91-3.33) mmol/l; day 1 LDL-C = 1.0 (0.58-1.50) mmol/l; day 3 LDL-C = 1.04 (0.64-1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26-2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p < 0.001 and p = 0.007, respectively). No link was found between prior lipid profile and mortality.

Conclusions: We showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.
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http://dx.doi.org/10.1186/s13613-021-00800-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815878PMC
January 2021

Priorities in peritonitis.

Curr Opin Crit Care 2021 04;27(2):201-207

Université de Paris, UFR Denis Diderot.

Purpose Of Review: Timely and adequate management are the key priorities in the care of peritonitis. This review focuses on the cornerstones of the medical support: source control and antiinfective therapies.

Recent Findings: Peritonitis from community-acquired or healthcare-associated origins remains a frequent cause of admission to the ICU. Each minute counts for initiating the proper management. Late diagnosis and delayed medical care are associated to dramatically increased mortality rates. The diagnosis of peritonitis can be difficult in these ICU cases. The signs of organ failures are more relevant than biological surrogates. A delayed source control and a late anti-infective therapy are of critical importance. The quality of source control and medical management are other key elements of the prognosis. The conventional rules applied for sepsis are applicable for peritonitis, including hemodynamic support and anti-infective therapy. Growing proportions of multidrug resistant pathogens are reported from surgical samples, mainly related to Gram-negative bacteria. The increasing complexity in the care of these critically ill patients is a strong incentive for a multidisciplinary approach.

Summary: Early clinical diagnosis, timely and adequate source control and antiinfective therapy are the essential pillars of the management of peritonitis in ICU patients.
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http://dx.doi.org/10.1097/MCC.0000000000000805DOI Listing
April 2021

High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects.

Int J Mol Sci 2020 Dec 24;22(1). Epub 2020 Dec 24.

Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1188, Diabète Athérothrombose Réunion Océan Indien (DéTROI), Reunion Island University, 97411 Saint-Denis de La Réunion, France.

High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.
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http://dx.doi.org/10.3390/ijms22010106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796353PMC
December 2020

Current management of necrotizing soft-tissue infections.

Curr Opin Infect Dis 2021 Apr;34(2):89-95

Université de Paris, UFR Denis Diderot.

Purpose Of Review: The aim of the article is to present recent epidemiological, microbiological, and clinical data for the surgical, antimicrobial, and adjunctive management of necrotizing soft-tissue infections (NSTI).

Recent Findings: NSTI can be caused by a broad variety of organisms. Reports about NSTI caused by multidrug-resistant bacteria are increasing. Owing to the rareness of NSTI, general clinical awareness is low and prompt diagnosis is often delayed. New diagnostic instruments (scoring systems, MRI) have either a low accuracy or are time consuming and cannot guide clinicians reliable currently. The value of adjunctive measures (intravenous immunoglobulin, hyperbaric oxygen therapy) is uncertain as well. Morbidity and mortality in NSTI remain high, ranging from 20 up to over 30%.

Summary: Early radical surgical debridement and empirical broad-spectrum antimicrobial treatment remain the cornerstones of therapy in NSTI. Further clinical research is necessary to shorten diagnostic pathways and to optimize surgical, antimicrobial, and adjunctive treatment.
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http://dx.doi.org/10.1097/QCO.0000000000000700DOI Listing
April 2021

Cotrimoxazole and clindamycin in skin and soft tissue infections.

Curr Opin Infect Dis 2021 Apr;34(2):63-71

Department of General, Visceral and Thoracic Surgery, Klinikum Hannoversch Muenden and Goettingen University, Muenden, Germany.

Purpose Of Review: The aim of this study was to present recent microbiological, experimental, clinical and tolerance data for cotrimoxazole and clindamycin in the specific field of skin and soft tissue infections (SSTIs).

Recent Findings: Staphylococcus aureus and streptococci remain the leading cause of SSTIs. Cotrimoxazole is a good anti-Gram-positive agent with preserved activity against methicillin-susceptible and methicillin-resistant S. aureus (MRSA) and streptococci. Although clindamycin has good methicillin-susceptible S. aureus activity, a growing number of resistant MRSA and streptococci have been reported. Strong experimental data support the antitoxin activity of clindamycin, but clinical observations remain scarce. Several recent randomized trials involving cotrimoxazole and/or clindamycin demonstrate the efficacy and tolerance of both drugs. The oral formulation of both drugs may facilitate the implementation of early switch and early discharge protocols in clinical practice.

Summary: Recent publications demonstrate that cotrimoxazole and clindamycin remain reliable and realistic therapeutic approaches for SSTIs.
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http://dx.doi.org/10.1097/QCO.0000000000000698DOI Listing
April 2021

Characteristics associated with COVID-19 or other respiratory viruses' infections at a single-center emergency department.

PLoS One 2020 3;15(12):e0243261. Epub 2020 Dec 3.

INSERM, IAME, Université de Paris, Paris, France.

Background: Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs.

Methods: We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR.

Results: 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively.

Conclusion: Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243261PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714208PMC
December 2020

Emergence of Imipenem Resistance in a CpxA-H208P-Variant-Producing Clinical Isolate.

Microb Drug Resist 2021 Jun 24;27(6):747-751. Epub 2020 Nov 24.

IAME, UMR 1137, INSERM, Université de Paris, Paris, France.

The PmirS clinical isolate, which was susceptible to imipenem (0.5 μg/mL) and amikacin (1 μg/mL), was recovered from a bronchial aspirate of a patient who recently underwent lung transplantation. The PmirR clinical isolate, which exhibited resistance to imipenem (16 μg/mL) and amikacin (24 μg/mL), was isolated 3 weeks later from the same patient and the same specimen type. Using short-read sequencing technology, these isolates appeared to be genetically identical except the gene of the PmirR isolate that was mutated leading to the His-208-Pro substitution. The structural alteration was localized in the histidine kinase, adenylate cyclase, methyl accepting protein, phosphatase (HAMP) domain, which is involved in the signal transduction between the sensor kinase and the regulator response of the CpxA/CpxR two-component system (TCS). No significant defect in the growth rate was found between the PmirS and PmirR isolates. This study suggests that alteration in CpxA might confer imipenem and amikacin resistance in . This study brings new evidence that the TCS alteration could provide an adaptive capacity in a clinical context by conferring antibiotic resistance without fitness cost.
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http://dx.doi.org/10.1089/mdr.2020.0295DOI Listing
June 2021

Outcome of Lung Transplantation Using Grafts From Donors Over 65 Years of Age.

Ann Thorac Surg 2020 Nov 7. Epub 2020 Nov 7.

Department of Vascular Surgery, Thoracic Surgery, and Lung Transplantation, Bichat Hospital, University of Paris, Paris, France. Electronic address:

Background: The outcome of lung transplantation (LT) is correlated with donor selection. A donor age of 65 years is classically considered a contraindication to lung procurement, and the results of LT from elderly donors remain to be established.

Methods: This was a retrospective study of a prospectively maintained database including all LTs performed in a single institution (Bichat Hospital, University of Paris, Paris, France) from January 2014 to March 2019. Donors65 years of age or older were included in the elderly group, whereas donors younger than 65 years of age were included in the control group.

Results: The study group included 241 LTs, including 44 (18%) in the elderly group and 197 (82%) in the control group. As compared with the control group, the elderly group was characterized by the following: donors of shorter stature (166 cm vs 172 cm; P = .04) and with less smoking history (14% vs 40%; P = .001), less bronchoscopic abnormality (20% vs 36%; P = .042), and less chest opacity (16% vs 30%; P = .048); and recipients of shorter stature (166 cm vs 170 cm; P = .04) but with similar diagnoses and gravity. There was no significant difference between the groups in any of the outcomes studied, including primary graft dysfunction, 30-day mortality, 1-year survival, chronic lung allograft dysfunction-free survival, and overall survival. In univariate analysis, the Oto lung donor score was the only factor associated with 1-year survival (score of 6 in alive patients vs score of 7 in dead patients; P = .04); donor age 65 years old or older was not.

Conclusions: Carefully selected lung grafts from donors 65 years of age or older are associated with outcomes similar to those reported with grafts from younger donors Grafts from older donors thus provide an interesting option to expand the donor pool during a shortage.
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http://dx.doi.org/10.1016/j.athoracsur.2020.10.018DOI Listing
November 2020

Anti-infective therapy against SARS-CoV-2: some light at the end of the tunnel?

Anaesth Crit Care Pain Med 2020 12 20;39(6):695-697. Epub 2020 Oct 20.

Département d'Anesthésie-Réanimation, CHU Bichat-Claude Bernard, DMU PARABOL, HUPNVS, APHP, 75018 Paris France; Institut Pasteur, Inserm UMR 1222, 75015 Paris, France; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Biostatistics Research Branch, Division of Clinical Research, Bethesda, MD, USA.

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http://dx.doi.org/10.1016/j.accpm.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574899PMC
December 2020

Ousted health care workers because of COVID-19 infection: Back to work is not an easy move.

Anaesth Crit Care Pain Med 2021 06 7;40(3):100752. Epub 2020 Oct 7.

Anaesthesiology and critical care medicine department, DMU PARABOL, Bichat hospital, AP-HP, Paris, France; Paris University, Paris, France; Inserm UMR 1152, Paris University, Paris, France.

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http://dx.doi.org/10.1016/j.accpm.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540210PMC
June 2021

A strobe multicenter descriptive study of 55 infectious aortitis.

Medicine (Baltimore) 2020 Oct;99(40):e22422

Department of Internal Medicine, CHU Nantes, Nantes.

Infectious aortitis (IA) is a rare and severe disease. The treatment classically associates open surgery with prolonged antibiotic therapy. This study aimed to describe clinical characteristics, medical and surgical supports in a large and current series of IA.We conducted a retrospective multicenter study of native aorta IA, between 2000 and 2019. Inclusion criteria were the presence of a microorganism on blood culture, aortic sample or any other validated technique and structural anomaly in imaging.We included 55 patients (85% men), with a median age of 65. Microbiology data substantially differed from previous studies with 12 Gram-negative rods IA, of which only 3 due to Salmonella spp., 24 Gram-positive cocci IA of which 12 Streptococcus spp., and 18 IA due to intracellular growth and/or fastidious microorganisms, of which 8 Coxiella burnetii, 3 Treponema pallidum, and 5 tuberculosis suspicious cases. Fifteen patients (27%) presented with thoracic IA, 31 (56%) with abdominal IA, and 9 (16%) with thoraco-abdominal IA. Eight patients had no surgery, 41 underwent open surgery, only 4 endovascular aneurysm repair, and 2 a combination of these 2 techniques. Nine patients died before 1-month follow-up. There was no difference in the mortality rate between the different types of germ or localization of IA.The variety of germs involved in IA increases. Positron emission tomography-computed tomography scan is a very useful tool for diagnosis. Surgery is still mainly done in open approach and a prospective multicenter study seems necessary to better determine the place of endovascular aneurysm repair versus open surgery.
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http://dx.doi.org/10.1097/MD.0000000000022422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535642PMC
October 2020

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

PLoS One 2020 24;15(9):e0239573. Epub 2020 Sep 24.

Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France.

Introduction: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection.

Methods: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP.

Results: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006).

Conclusion: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239573PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514065PMC
October 2020

Reducing Intraoperative Hypotension Using a Machine Learning-Derived Early Warning System.

JAMA 2020 08;324(8):806-807

Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, Paris, France.

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http://dx.doi.org/10.1001/jama.2020.9049DOI Listing
August 2020

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia.

Crit Care 2020 06 19;24(1):366. Epub 2020 Jun 19.

Université de Paris, IAME, INSERM, Paris, F-75018, France.

Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients.

Methods: In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available.

Results: We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73-88%) and specificity of 99% (95% CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods.

Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.
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http://dx.doi.org/10.1186/s13054-020-03067-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303941PMC
June 2020

Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients.

Am J Respir Crit Care Med 2020 09;202(6):822-829

Paris University, Paris, France.

Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function. In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid. A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m at ICU admission. In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8];  = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8];  < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1). Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.
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http://dx.doi.org/10.1164/rccm.201910-1950OCDOI Listing
September 2020

Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

Ann Intensive Care 2020 Jun 8;10(1):75. Epub 2020 Jun 8.

CH Argenteuil, réanimation polyvalente, 69 rue du Lieutenant-Colonel Prudhon, Argenteuil, France.

Background: Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (C) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the C should be 64-80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target C/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections.

Methods: Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and C measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min-max].

Results: 93 patients with 98 GNB-documented infections were included. The median C was 55.2 mg/L [12.2-165.7] and the median MIC was 2 mg/L [0.19-16]. C/MIC ratio ≥ 8 was achieved in 87 patients (88.8%) while a C ≥ 64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between C/MIC ratio and clinical outcome at D8 and D28.

Conclusion: According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.
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http://dx.doi.org/10.1186/s13613-020-00685-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276966PMC
June 2020