Procalcitonin combined to point of care molecular respiratory panel testing for antibiotic stewardship in the emergency room: the PROARRAY study

Introduction: Molecular syndromic respiratory panel (RP) or procalcitonin (PCT)-driven algorithms have reported conflicting efficacy for antibiotic ATB) stewardship in LRTI. We hypothesized that combining real-time PCT measurement and virus identification would reduce ATB exposition in LRTI suspicions presenting to the emergency department (ED). Method(s): PROARRAY study is a prospective, randomized interventional trial, conducted in the adult ED of an academic 1600-bed hospital. Patients attending the ED with a suspicion of LRTI were randomized into the intervention arm (systematic PCT measurement and point of care BIOFIRE RP2plus (then 2.1) testing, with the recommendation to withhold or withdraw ATB if PCT < 0.25 mug/L and/or identification of a virus) or a standard of care (SOC) arm. The primary endpoint was the duration of antibiotic exposure in the first 28 days. Result(s): 451 patients were randomized (intervention: 225, SOC: 226), mean age 62.5 +/- 19.4 years, hospitalization rate 59.9%, mean length of stay 7.4 +/- 8.4 days. Main diagnoses were CAP (n = 129), COVID-19 (n = 91), AECOPD (n = 31). The BIOFIRE RP2.1plus identified at least one viral species in 112 patients (49.8%). The duration of ATB exposition in ITT population was 6.00 [0.00;9.00] and 5.00 [0.00-9.00] days in the SOC and interventional arm respectively (p = 0.71). ATB was started in 31.3% and 34.1% respectively (p = 0.54). ATB exposure was below 6 days in 100 (47.2%) and 108 patients (50.59%) respectively (p = 0.58). Conclusion(s): Displaying real-time PCT and RP results failed to significantly reduce the ATB exposition in LRTI suspicions. However, the ATB duration and rate of initiation were already low in SOC arm, which comprised PCT measurement in routine in our ED. Routine PCT measurement probably participated to the lower median ATB duration (6.0 days) than hypothesized (9.0 days) and argues for the main contribution of PCT in ATB stewardship. Moreover, as the intervention was done at ED's level, we did not control for ATB stewardship in wards for inpatients.

Which biomarker(s) to predict worsening of SARS-CoV2 infection? An ancillary study from the COVIDeF cohort

Introduction: COVID-19 has been responsible for millions of deaths and intensive care unit (ICU) admissions all over the world. Identifying the patients at risk of developing a severe form is crucial for an optimized orientation and allocation of resources. The main objective of our study was to identify among a selection of biomarkers, those predictive of short term worsening in COVID-19. Method(s): This is an ancillary study using clinical data and collected biobanking from the multicentric cohort study COVIDeF, which included prospectively from March 31th 2020 to March 30th 2021, patients admitted with a suspected Sars-CoV2 infection in the Assistance- Publique-Hopitaux de Paris network, France. Patients with confirmed COVID-19 were divided in 2 groups: a severe (ICU admission or invasive or non-invasive ventilation or ARDS or death) and a control group (no worsening). The routine blood tests and following biomarkers: troponin, C Reactive Protein (CRP), procalcitonin, Mild- Regional pro-Adrenomedulin (MR-proADM), pro-endothelin, SuPAR, NT-proBNP, calprotectin, PF4, D-dimers, were measured in plasma or serum and compared between both groups using a conditional logistic regression. Result(s): Among the 1040 first patients included in the COVIDEF cohort, we selected 512 patients having a blood sample drawn at admission before worsening, of which 60 secondarily worsened (severe group). The mean age was 59.5 (+/- 19.5) years and 50.2% were females. Among the biomarkers tested, three were independently associated with worsening: CRP (mg/l) OR 1.01 [IC 1.01-1.02], procalcitonin (ng/ml) OR 0.4428 [0.21-0.95] and MR-proADM (pg/ml) OR 3.012 [1.06-8.53]. Conclusion(s): Among a selection of biomarkers of interest, MRproADM appears to best identify at admission COVID-19 patients at risk of worsening. Future interventional studies should test the efficacy and security of this biomarker to rule-in and rule-out severe outcome and the usefulness for allocating resources.

Retour d'expérience sur Covisan : un dispositif médicosocial pour casser les chaînes de transmission de la Covid-19

Covisan a été mis en place à partir du 14 avril 2020 au niveau de quatre sites pilotes de l'Assistance publique-Hôpitaux de Paris (APHP) pour casser les chaînes de transmission au SARS-CoV-2 selon un modèle original déjà éprouvé en Haïti pour éliminer le choléra dans les années 2010. Le dispositif consiste en un dépistage systématique des cas possibles de Covid-19, un accompagnement dans leur confinement et une prise en charge de leurs proches. Des équipes mobiles se sont déplacées au domicile des cas contacts afin d'évaluer les possibilités d'un isolement au domicile, de proposer des aides matérielles (courses, blanchisserie, hébergement externalisé) et de dépister leurs proches. Au 17 juin 2020, 6 376 patients ont été orientés vers Covisan, parmi lesquels 153 avaient une RT-PCR (reverse transciptase polymerase chain reaction) positive au SARSCoV-2. Covisan a permis un partenariat ville–hôpital innovant, en impliquant de multiples acteurs (personnels soignants, administratifs, logisticiens, métiers de service). Les autorités sanitaires se sont d'ailleurs inspirées de ce modèle pour lutter contre l'épidémie en mettant en place le contact tracing. Covisan, qui a appris en marchant, a également rencontré quelques difficultés, en particulier au niveau de la gestion des différents statuts des personnels ainsi qu'au niveau de la communication interne et externe.Alternate abstract: COVISAN was set up from April 14, 2020 at 4 pilot sites of Assistance publique-Hôpitaux de Paris (APHP) to break the sequence of transmission of SARSCoV-2 according to an original model already proven in Haiti to eradicate cholera in the 2010s. This device relies on a systematic screening of the possible COVID-19 cases, assistance in their containment and care for their close relatives. Mobile teams carried out home visits to evaluate the possibilities of home confinement, to propose material help (errands, laundry, outsourcing accommodation) and to propose a screening of their relatives. By June 17, 2020, 6376 patients have been moved towards COVISAN, and 153 had a positive RT–PCR to SARS-CoV-2. COVISAN has made possible an innovating town-hospital partnership, involving multiple actors (nursing staff, administrative staff, logistician, and service professions). Health authorities have decided to model their strategy to control the SARSCoV-2 spread closely to COVISAN's, and implemented "contact tracing”. COVISAN that learned by doing, has also encountered some difficulties, mainly concerning the different staff statutes and also with the internal and external communication.

Le dosage de la procalcitonine peut-il être utile à la prise en charge d'une infection à SARS-CoV-2 aux urgences et en réanimation ?

De nombreuses études d'impact ont validé l'intérêt du dosage de la procalcitonine pour rationaliser les antibiothérapies dans les infections respiratoires basses. En l'absence d'étude prospective interventionnelle spécifiquement chez les patients atteints de Covid-19, le dosage de la procalcitonine peut cependant être utilisé aux urgences comme dans les autres IRB pour l'aide à la décision d'antibiothérapie. La majorité des infections à SARS-CoV-2 non compliquées ont des valeurs de procalcitonine inférieures à 0,25 μg/l. Parallèlement, des concentrations supérieures à 0,5 μg/l peuvent traduire un risque d'évolution vers une forme grave et/ou une co-infection bactérienne. En soins critiques, la procalcitonine est prometteuse chez les patients avec un syndrome de détresse respiratoire aiguë lié à la Covid. Chez ces patients, la pertinence de l'antibiothérapie est à reconsidérer quotidiennement, compte tenu du risque d'infection bactérienne qui évolue tout au long de séjours souvent prolongés, afin de réduire la sélection d'espèces résistantes et de limiter les toxicités.Alternate : Numerous interventional studies have validated the usefulness of the dosage of procalcitonin for antibiotic stewardship in lower respiratory tract infections (LRTI). Despite the absence of prospective interventional trials specifically for Covid-19 patients, the measurement of procalcitonin can be part of the standard of care in the emergency room as well as in other LRTIs to help with antibiotic decisions. Most non-complicated SARS-CoV-2 infections have procalcitonin concentrations < 0.25 μg/l. Furthermore, concentrations > 0.5 μg/l are usually associated with the risk of severe outcome and/or bacterial co-infection. In intensive care units, procalcitonin is promising in patients with acute respiratory distress syndrome due to Covid-19. In those patients, the prescription of antibiotics must be daily reconsidered, in that the risk of bacterial infection is evolving all along the long-lasting duration of stay, in order to limit the selection of resistant strains and limit antibiotic toxicity.

Retour d'expérience sur la réorganisation d'un service d'urgence de centre hospitalo-universitaire en réponse à l'épidémie de Covid-19

Depuis décembre 2019 le monde a dû faire face à une nouvelle maladie nommée : Covid-19. Sa dissémination rapide a imposé à l'Organisation mondiale de la santé de déclarer le statut de pandémie mondiale. La réponse des services d'urgence français à cette catastrophe sanitaire était cruciale. Elle a dû intégrer la notion d'urgence inhérente à la multiplication des nouveaux cas, mais également la nécessité d'une réponse organisée et d'une modulation continuelle de celle-ci sur une période jusqu'alors inconnue. Nous présentons dans cet article un schéma d'organisation et un retour d'expérience, d'un service d'urgence de centre hospitalier universitaire (CHU), établissement de santé de référence (ESR) pour le risque épidémique et biologique pour faire face à l'épidémie. Nous exposons les grandes lignes d'une réorganisation structurelle de notre service, la modification du circuit patient en amont de la filière des urgences et en aval, mais également la modification de nos pratiques de soins. Cette réorganisation a dû prendre en compte la notion de contagiosité avec la nécessité d'une séparation précoce en deux filières de soins, effectuée grâce à un processus de prétriage et de triage en amont de la filière. L'un des points clés de cette organisation a été l'évolutivité des définitions des cas suspects au cours du temps et au gré de l'évolution de la connaissance de ce virus et de sa dissémination. Cela a nécessité une adaptabilité de notre filière et une réévaluation quasi quotidienne de cette organisation associée à une information, une formation et un entraînement du personnel de cette structure.Alternate : Since December 2019 the world has had to face a new disease called: Coronavirus disease-19 (COVID-19). Its rapid spread required theWorld Health Organization (WHO) to declare the status of a global pandemic. The response of the French emergency services to this health disaster was crucial. It had to integrate the notion of emergency, inherent to the new case's multiplication, but also the need of an organized response and a continual modulation of it, over an unknown period. In this article, we present an organizational diagram and feedback to the COVID-19 outbreak from an emergency department of an academic hospital, a reference health establishment (ESR) for epidemic and biological risk. We report the main lines of a structural reorganization of our service, the modification of the patient circuit upstream of the emergency department and downstream, but also the modification of our care practices. This reorganization had to take the notion of contagiousness with the need of an early separation into two care lines, with a pre-triage and triage process upstream of the line. One of the key points of this organization has been the evolving nature of the definitions of suspected cases over time and of the virus knowledge and its spread. This has required an adaptability of our sector and a daily reassessment of this organization associated with information, training and staff training of this structure.

Is procalcitonin measurement useful for SARS-CoV-2 infection management in the emergency department as well as in the ICU?

Numerous interventional studies have validated the usefulness of the dosage of procalcitonin for antibiotic stewardship in lower respiratory tract infections (LRTI). Despite the absence of prospective interventional trials specifically for Covid-19 patients, the measurement of procalcitonin can be part of the standard of care in the emergency room as well as in other LRTIs to help with antibiotic decisions. Most non-complicated SARS-CoV-2 infections have procalcitonin concentrations < 0.25 μg/l. Furthermore, concentrations > 0.5 μg/l are usually associated with the risk of severe outcome and/or bacterial co-infection. In intensive care units, procalcitonin is promising in patients with acute respiratory distress syndrome due to Covid-19. In those patients, the prescription of antibiotics must be daily reconsidered, in that the risk of bacterial infection is evolving all along the long-lasting duration of stay, in order to limit the selection of resistant strains and limit antibiotic toxicity.

Sharing of experience about COVISAN: A medical and social system to break the sequence of transmission of COVID-19

COVISAN was set up from April 14, 2020 at 4 pilot sites of Assistance publique-Hôpitaux de Paris (APHP) to break the sequence of transmission of SARSCoV-2 according to an original model already proven in Haiti to eradicate cholera in the 2010s. This device relies on a systematic screening of the possible COVID-19 cases, assistance in their containment and care for their close relatives. Mobile teams carried out home visits to evaluate the possibilities of home confinement, to propose material help (errands, laundry, outsourcing accommodation) and to propose a screening of their relatives. By June 17, 2020, 6376 patients have been moved towards COVISAN, and 153 had a positive RT-PCR to SARS-CoV-2. COVISAN has made possible an innovating town-hospital partnership, involving multiple actors (nursing staff, administrative staff, logistician, and service professions). Health authorities have decided to model their strategy to control the SARSCoV-2 spread closely to COVISAN's, and implemented “contact tracing”. COVISAN that learned by doing, has also encountered some difficulties, mainly concerning the different staff statutes and also with the internal and external communication.

Faible taux de fumeurs actifs quotidiens parmi les malades atteints de COVID-19 symptomatique

Introduction Alors que la pandémie de COVID-19 reste encore active, l’identification de facteurs pronostiques de la maladie reste un enjeu important. Parmi ceux-ci, le tabagisme a un rôle qui reste controversé. Nous avons donc voulu vérifier si le taux de fumeur chez les patients COVID-19 était différent de celui de la population française. Matériels et méthodes Nous avons recueilli par entretien de façon systématique chez les patients COVID-19 ambulatoires (du 28/02 au 30/03/2020) et hospitalisés (du 23/03 au 09/04/2020) d’un unique centre hospitalo-universitaire, leur consommation actuelle de tabac, de e-cigarette et de substituts nicotiniques. Les taux de fumeurs actifs quotidiens parmi les patients ambulatoires et hospitalisés ont été comparés à ceux de la population générale française de 2019 après standardisation pour l’âge et le sexe. Résultats Le groupe des patients hospitalisés était composé de 340 patients, âge médian 66 ans : 203 hommes (59,7 %) et 137 femmes (40,3 %), âge médian pour les deux sexes 66 ans, avec un taux de fumeurs actifs quotidiens de 4,1 %, IC95 % [2,3–6,9] (5,4 % des hommes, 2,2 % des femmes). Le groupe des patients ambulatoires était composé de 139 patients, âge médian 44 ans : 62 hommes (44,6 %, âge médian 43 ans), et 77 femmes (55,4 %, âge médian 44 ans). Le taux de fumeurs actifs quotidiens était de 6,1 % ;IC95 % [2,7–11,6] (5,1 % d’hommes, et 6,8 % de femmes). Dans la population générale française de 2019, le taux de fumeurs actifs quotidiens était de 24,0 % (27,5 % chez les hommes, 20,7 % chez les femmes). Chez les patients hospitalisés, les fumeurs actifs quotidiens représentaient 2,2 % et 3,4 % des 45 patients décédés et des 29 patients transférés en soins intensifs respectivement. Le taux de fumeurs actifs quotidiens était significativement plus faible chez les patients COVID-19 que celui de la population générale française de 2019 après standardisation par âge et par sexe, avec un ratio d’incidence standardisé calculé à 0,24 [0,12–0,48] pour les patients ambulatoires et de 0,24 [0,14–0,40] pour les patients hospitalisés. Conclusion Le taux de fumeurs actifs quotidiens est faible parmi les malades atteints de COVID-19 symptomatique.