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Rationale: Few population-based data are available regarding nontuberculous mycobacteria (NTM) pulmonary disease epidemiology and prognosis. Objectives: To examine NTM pulmonary colonization incidence, disease incidence, and prognostic factors. Methods: All adults in Denmark with at least one NTM-positive pulmonary specimen during 1997 to 2008 were identified using national medical databases and were categorized as having possible or definite NTM disease or colonization. Measurements and Main Results: We calculated annual age-standardized NTM incidence rates and adjusted hazard ratios (HR) of death associated with patient age, sex, comorbidity, NTM species, and NTM disease status. Of 1,282 adults with 2,666 NTM-positive pulmonary specimens, 335 (26%) had definite NTM disease, 238 (19%) possible disease, and 709 (55%) colonization only. NTM incidence rates decreased until 2002, followed by an increase from 2003 to 2008 (mean annual rate per 100,000 person-years: NTM colonization, 1.36; NTM disease, 1.08). Five-year mortality after definite NTM disease was 40.1%. After controlling for potential confounders, 5-year mortality for definite NTM disease was slightly higher than for NTM colonization (adjusted hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90-1.51). Mycobacterium xenopi was associated with worse prognosis (adjusted HR, 1.51; 95% CI, 0.99-2.33) than the reference Mycobacterium avium complex. High comorbidity level (HR, 2.97), age greater than or equal to 65 years (HR, 9.17), and male sex (female sex HR, 0.73) were predictors of death. Conclusions: NTM disease incidence has remained unchanged in Denmark over the past 12 years. Patients with NTM colonization and disease have similarly poor prognosis. Negative prognostic factors include high levels of comorbidity, advanced age, male sex, and M. xenopi. [ABSTRACT FROM AUTHOR]

Background: Owing to its low incidence, the management of Mycobacterium xenopi pulmonary infections is not clearly defined. A multicentre retrospective study was performed to describe the features of the disease and to evaluate its prognosis. Methods: All patients with M xenopi satisfying the 1997 ATS/IDSA criteria from 13 hospitals in north-east France (1983-2003) were included in the study. Clinical, radiological and bacteriological characteristics and data on the management and outcome were collected. Results: 136 patients were included in the analysis, only 12 of whom presented with no co-morbidity. Three types of the disease were identified: (1) a classical cavitary form in patients with pre-existing pulmonary disease (n = 39, 31%); (2) a solitary nodular form in immunocompetent patients (n = 41, 33%) and (3) an acute infiltrate form in immunosuppressed patients (n = 45, 36%). 56 patients did not receive any treatment; the other 80 patients received first-line treatment containing rifamycin (87.5%), ethambutol (75%), isoniazid (66.2%), clarithromycin (30%) or fluoroquinolones (21%). After a follow-up of 36 months, 80 patients (69.1%) had died; the median survival was 16 months (range 10-22). Two independent prognostic factors were found: the acute infiltrate form was associated with a bad prognosis (hazard ratio 2.6, p = 0.001) and rifamycin-containing regimens provided protection (hazard ratio 0.325, p = 0.006). Clarithromycin-containing regimens did not improve the prognosis. Conclusions: In contrast to recent guidelines, this study showed three different types of the disease (cavitary, nodular or diffuse infiltrate forms) with a different prognosis. In order to improve survival, all patients with M xenopi infection should be treated with a rifamycin-containing regimen. The usefulness of clarithromycin remains to be evaluated. [ABSTRACT FROM AUTHOR]

Background: The 2023 Duke-ISCVID and 2023 ESC classifications have recently issued independent diagnostic criteria for infective endocarditis (IE), updating the 2015 ESC criteria., Objectives: The specificity of the 2023 ESC criteria should be evaluated and compared to the two other classifications in IE suspected patients., Methods: We retrospectively collected the characteristics of patients hospitalised in Bichat University Hospital, in 2021, who had been evaluated for suspicion of IE, and in whom IE diagnosis was finally rejected. All were classified by 2015 ESC, 2023 Duke-ISCVID, and 2023 ESC., Results: In total 130 patients were analysed. Mean age was 62 years, 64.6% were male, 30.0% had prosthetic cardiac valve or valve repair, 16.2% had cardiac implanted electronic device, and 23.1% other cardiac conditions. Overall, 2, 5 and 5 patients were falsely classified as definite IE with the 2015 ESC, 2023 Duke-ISCVID and 2023 ESC criteria, respectively. The corresponding specificities were 99% (95% CI [94%; 100%], 96% (95% CI [91%; 99%]), and 96% (95% CI [91%; 99%])., Conclusion: The 2023 ESC and the 2023 Duke-ISCVID criteria are highly specific, although slightly less than the 2015 ESC criteria, for ruling out the diagnosis of definite IE.HIGHLIGHTS2023 Duke-ISCVID and 2023 ESC criteria are recently issued diagnostic classifications2023 ESC criteria have an excellent specificity, equivalent to the 2023 Duke-ISCVID one2023 ESC criteria and the 2023 Duke-ISCVID are less specific than the 2015 ESC criteriaSpecificities were quite similar according to the nature of the cardiac valve (native or prosthetic valve) or the duration of antibiotic therapy.

Background: Suboptimal use of antimicrobials is a driver of antimicrobial resistance in West Africa. Clinical decision support systems (CDSSs) can facilitate access to updated and reliable recommendations., Objective: This study aimed to assess contextual factors that could facilitate the implementation of a CDSS for antimicrobial prescribing in West Africa and Central Africa and to identify tailored implementation strategies., Methods: This qualitative study was conducted through 21 semistructured individual interviews via videoconference with health care professionals between September and December 2020. Participants were recruited using purposive sampling in a transnational capacity-building network for hospital preparedness in West Africa. The interview guide included multiple constructs derived from the Consolidated Framework for Implementation Research. Interviews were transcribed, and data were analyzed using thematic analysis., Results: The panel of participants included health practitioners (12/21, 57%), health actors trained in engineering (2/21, 10%), project managers (3/21, 14%), antimicrobial resistance research experts (2/21, 10%), a clinical microbiologist (1/21, 5%), and an anthropologist (1/21, 5%). Contextual factors influencing the implementation of eHealth tools existed at the individual, health care system, and national levels. At the individual level, the main challenge was to design a user-centered CDSS adapted to the prescriber's clinical routine and structural constraints. Most of the participants stated that the CDSS should not only target physicians in academic hospitals who can use their network to disseminate the tool but also general practitioners, primary care nurses, midwives, and other health care workers who are the main prescribers of antimicrobials in rural areas of West Africa. The heterogeneity in antimicrobial prescribing training among prescribers was a significant challenge to the use of a common CDSS. At the country level, weak pharmaceutical regulations, the lack of official guidelines for antimicrobial prescribing, limited access to clinical microbiology laboratories, self-medication, and disparity in health care coverage lead to inappropriate antimicrobial use and could limit the implementation and diffusion of CDSS for antimicrobial prescribing. Participants emphasized the importance of building a solid eHealth ecosystem in their countries by establishing academic partnerships, developing physician networks, and involving diverse stakeholders to address challenges. Additional implementation strategies included conducting a local needs assessment, identifying early adopters, promoting network weaving, using implementation advisers, and creating a learning collaborative. Participants noted that a CDSS for antimicrobial prescribing could be a powerful tool for the development and dissemination of official guidelines for infectious diseases in West Africa., Conclusions: These results suggest that a CDSS for antimicrobial prescribing adapted for nonspecialized prescribers could have a role in improving clinical decisions. They also confirm the relevance of adopting a cross-disciplinary approach with participants from different backgrounds to assess contextual factors, including social, political, and economic determinants., (©Nathan Peiffer-Smadja, Sophie Descousse, Elsa Courrèges, Audrey Nganbou, Pauline Jeanmougin, Gabriel Birgand, Séverin Lénaud, Anne-Lise Beaumont, Claire Durand, Tristan Delory, Josselin Le Bel, Elisabeth Bouvet, Sylvie Lariven, Eric D'Ortenzio, Issa Konaté, Marielle Karine Bouyou-Akotet, Abdoul-Salam Ouedraogo, Gisèle Affoue Kouakou, Armel Poda, Corinne Akpovo, François-Xavier Lescure, Aristophane Tanon. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.10.2024.)

Background: Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection., Methods: This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48 h., Results: One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one-month mortality were age and maximum oxygen flow during hospitalization., Conclusion: RSV-associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. PL has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Moderna, Pfizer, Sanofi Pasteur and support for attending meetings and/or travel from Astrazeneca, Pfizer and Sanofi Pasteur. VB received support for attending meetings from LFB and worked with the advisory boards of Biotest, Novartis and Takeda., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients., Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used., Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course., Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Astrid VABRET disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from ANOFI, 10.13039/501100003103ASTRA ZENECA, MODERNA, and participation on a Data Safety Monitoring Board from SANOFI, 10.13039/100030732MSD, MODERNA and GSK. Frederic Schlemmer disclosed consulting fees from 10.13039/100004319Pfizer, payment or honoraria for lectures, presentations from 10.13039/100005564Gilead, and participation on a Data Safety Monitoring Board from Boerhinger Ingelheim, 10.13039/100019719Chiesi, Elivie, 10.13039/100005564Gilead, 10.13039/100004330GlaxoSmithKline and Oxyvie. Anne Bergeron disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from Astra Zeneca and 10.13039/100004336Novartis, and participation on a Data Safety Monitoring Board from Enanta. Anahita Rouzé disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from 10.13039/100030732MSD, 10.13039/100005564Gilead, Mundipharma. Blandine RAMMAERT disclosed payment or honoraria for lectures, presentations from Gilead. Cedric Daubin disclosed support for attending meetings and/or travel from 10.13039/100005564Gilead. Nicolas Terzi disclosed payment or honoraria for lectures, presentations from 10.13039/100004319Pfizer and Boehringher Inghelheim, and support for attending meetings and/or travel from 10.13039/100005564Gilead. Quentin Philippot disclosed payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from 10.13039/100005564Gilead and Elsevier, and grants or contracts from APHP, 10.13039/501100017007ARS Ile de France and 10.13039/501100001677Inserm 10.13039/501100007492Fondation Bettencourt Schueller, and support for the present manuscript from SOS Oxygen. Other authors did not disclose competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Enterococcus faecalis is the third micro-organism causing endocarditis and is associated with a significant relapse rate. The objective of this study was to describe the management of patients with Enterococcus faecalis endocarditis (EE) and its implication for relapses., Methods: We conducted a monocentric, retrospective analysis of all patients hospitalized for EE including endocarditis or infection of cardiac implantable electronic device defined by the modified ESC 2015 Duke criteria in a referral centre in Paris, France., Results: Between October 2016, and September 2022, 54 patients with EE were included, mostly men ( n  = 40, 74%) with a median age of 75 [68-80] years. A high risk for infective endocarditis (IE) was found in 42 patients (78%), including 14 (26%) previous histories of IE, and 32 (59%) histories of valvular cardiac surgery. The aortic valve was the most frequently affected ( n  = 36, 67%). Combination therapy was mainly amoxicillin-ceftriaxone during all the curative antibiotic therapy duration ( n  = 31, 57%). Surgery was indicated for 40 patients (74%), but only 27 (50%) were operated on, mainly due to their frailty. Among the 17 deaths (32%), six (11%) happened during the first hospitalization for EE. A suppressive antibiotic treatment was initiated in 15 (29%) patients, mostly because of not performing surgery. During the 6-year study period an EE relapse occurred in three (6%) patients., Conclusions: EE is a worrying disease associated with a high risk of relapse and significant mortality. Suppressive antibiotic therapy could be a key treatment to limit the occurrence of relapses., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Competing Interests: The authors disclose no completing interests

During the coronavirus disease 2019 (COVID-19) pandemic, several clinical prognostic scores have been proposed and evaluated in hospitalized patients, relying on variables available at admission. However, capturing data collected from the longitudinal follow-up of patients during hospitalization may improve prediction accuracy of a clinical outcome. To answer this question, 327 patients diagnosed with COVID-19 and hospitalized in an academic French hospital between January and July 2020 are included in the analysis. Up to 59 biomarkers were measured from the patient admission to the time to death or discharge from hospital. We consider a joint model with multiple linear or nonlinear mixed-effects models for biomarkers evolution, and a competing risks model involving subdistribution hazard functions for the risks of death and discharge. The links are modeled by shared random effects, and the selection of the biomarkers is mainly based on the significance of the link between the longitudinal and survival parts. Three biomarkers are retained: the blood neutrophil counts, the arterial pH, and the C-reactive protein. The predictive performances of the model are evaluated with the time-dependent area under the curve (AUC) for different landmark and horizon times, and compared with those obtained from a baseline model that considers only information available at admission. The joint modeling approach helps to improve predictions when sufficient information is available. For landmark 6 days and horizon of 30 days, we obtain AUC [95% CI] 0.73 [0.65, 0.81] and 0.81 [0.73, 0.89] for the baseline and joint model, respectively (p = 0.04). Statistical inference is validated through a simulation study., (© 2023 Wiley-VCH GmbH.)

Since the beginning of the COVID-19 pandemic, few studies have focused on crisis management of multiple services within one hospital over several waves of the pandemic. The purpose of this study was to provide an overview of the COVID-19 crisis response of a Parisian referral hospital which managed the first three COVID cases in France and to analyze its resilience capacities. Between March 2020 and June 2021, we conducted observations, semi-structured interviews, focus groups, and lessons learned workshops. Data analysis was supported by an original framework on health system resilience. Three configurations emerged from the empirical data: 1) reorganization of services and spaces; 2) management of professionals' and patients' contamination risk; and 3) mobilization of human resources and work adaptation. The hospital and its staff mitigated the effects of the pandemic by implementing multiple and varied strategies, which the staff perceived as having positive and/or negative consequences. We observed an unprecedented mobilization of the hospital and its staff to absorb the crisis. Often the mobilization fell on the shoulders of the professionals, adding to their exhaustion. Our study demonstrates the capacity of the hospital and its staff to absorb the COVID-19 shock by putting in place mechanisms for continuous adaptation. More time and insight will be needed to observe whether these strategies and adaptations will be sustainable over the coming months and years and to assess the overall transformative capacities of the hospital.

Background: Human mpox is a viral disease caused by an Orthopoxvirus, human mpox virus (hMPXV), typically causing fever and a rash. Mpox has historically been endemic to parts of Central and West Africa, with small numbers of imported cases reported elsewhere, but starting May 2022 an unprecedented global outbreak caused by clade IIb hMPXV was reported outside traditionally endemic countries. This prompted the initiation of MOSAIC, a cohort study implemented in Europe and Asia that aims to describe clinical and virologic outcomes of PCR-confirmed hMPXV disease, including those who receive antiviral therapy. The focus of this article, however, is on describing the study protocol itself with implementation process and operational challenges., Methods: MOSAIC recruits participants of any age with laboratory-confirmed mpox disease who provide informed consent. Participants enrol in the cohort for a total of six months. Blood, lesion and throat samples are collected at several timepoints from the day of diagnosis or the first day of treatment (Day 1) until Day 28 for PCR detection of hMPXV. Clinical data are collected by clinicians and participants (via a self-completion questionnaire) for six months to characterize the signs and symptoms associated with the illness, as well as short- and more long-term outcomes., Discussion: The design and prompt implementation of clinical research response is key in addressing emerging outbreaks. MOSAIC began enrolment within two months of the start of the international mpox epidemic. Enrolment has been stopped and the last follow-up visits are expected in January 2024., Ictrp Registration: EU CT number: 2022-501132-42-00 (22/06/2022)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Pesonel E et al.)

Objectives: Few is known on pregnant women with mild COVID-19 managed in a community setting with a telemedicine solution, including their outcomes. The objective of this study is to evaluate the adverse fetal outcomes and hospitalization rates of pregnant COVID-19 outpatients who were monitored with the Covidom© telemedicine solution., Methods: A nested study was conducted on pregnant outpatients with confirmed COVID-19, who were managed with Covidom© between March and November 2020. The patients were required to complete a standard medical questionnaire on co-morbidities and symptoms at inclusion, and were then monitored daily for 30 days after symptom onset. Adverse fetal outcome was defined as a composite of preterm birth, low birthweight, or stillbirth, and was collected retrospectively through phone contact with a standardized questionnaire., Results: The study included 714 pregnant women, with a median age of 32.0 [29.0-35.0] and a median BMI of 23.8 [21.3-27.0]. The main comorbidities observed were smoking (53%), hypertension (19%). The most common symptoms were asthenia (45.6%), cough (40.3%) and headache (25.7%), as well as anosmia (28.4%) and agueusia (32.3%). Adverse fetal outcomes occurred in 64 (9%) cases, including 38 (5%) preterm births, 33 (5%) low birthweights, and 6 (1%) stillbirths. Hospitalization occurred in 102 (14%) cases and was associated with adverse fetal outcomes (OR 2.4, 95% CI 1.3-4.4)., Conclusions: Our study suggests that adverse fetal outcomes are rare in pregnant women with mild COVID-19 who are monitored at home with telemedicine. However, hospitalization for COVID-19 and pregnancy-induced hypertension are associated with a higher risk of adverse fetal outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dinh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI., Methods: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control., Results: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC 0-8h /MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT >MIC  = 100% and to 6% for AUC 0-24h /MIC > 60, even with high clindamycin dose., Conclusion: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab., Methods: We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death., Results: Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 μmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients., Conclusion: Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Infective endocarditis (IE) is characterized by low incidence but high mortality. Patients with a history of IE are at highest risk. Adherence to prophylaxis recommendations is poor. We sought to identify determinants of adherence to oral hygiene guidelines on IE prophylaxis in patients with a history of IE., Methods: Using data from the cross-sectional, single-centre POST-IMAGE study, we analysed demographic, medical and psychosocial factors. We defined patients as adherent to prophylaxis if they declared going to the dentist at least annually and brushing their teeth at least twice a day. Depression, cognitive status and quality of life were assessed using validated scales., Results: Of 100 patients enrolled, 98 completed the self-questionnaires. Among these, 40 (40.8%) were categorized as adherent to prophylaxis guidelines, and were less likely to be smokers (5.1% vs. 25.0%; P=0.02) or have symptoms of depression (36.6% vs. 70.8%; P<0.01) or cognitive decline (0% vs. 15.5%; P=0.05). Conversely, they had higher rates of: valvular surgery since the index IE episode (17.5% vs. 3.4%; P=0.04), searching for information on IE (61.1% vs. 46.3%, P=0.05), and considering themselves as adherent to IE prophylaxis (58.3% vs. 32.1%; P=0.03). Tooth brushing, dental visits and antibiotic prophylaxis were correctly identified as measures to prevent IE recurrence in 87.7%, 90.8% and 92.8% of patients, respectively, and did not differ according to adherence to oral hygiene guidelines., Conclusions: Self-reported adherence to secondary oral hygiene guidelines on IE prophylaxis is low. Adherence is unrelated to most patient characteristics, but to depression and cognitive impairment. Poor adherence appears related more to a lack of implementation rather than insufficient knowledge. Assessment of depression may be considered in patients with IE., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection., Methods: All consecutive patients with a polymerase chain reaction (PCR)-confirmed monkeypox infection seen in a French referral centre were included., Results: Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients., Conclusion: The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The prognosis of asthmatic outpatients with COVID-19 needs to be clarified. The objectives of this study were: 1) to investigate the characteristics and outcomes of asthmatic patients receiving initial ambulatory care and home monitoring for COVID-19 with Covidom, a telesurveillance solution; and 2) to compare the characteristics and outcomes between asthmatic and non-asthmatic patients., Methods: Inclusion criteria were age ≥18 years, suspected or confirmed COVID-19 diagnosis allowing initial ambulatory care, registration in Covidom between March 2020 and April 2021 and completion of the initial medical questionnaire. We compared clinical characteristics and outcomes between asthmatic and non-asthmatic patients, and we evaluated whether asthma was independently associated with clinical worsening (hospitalisation or death) within 30 days follow-up using a multivariate logistic regression model., Results: 33 815 patients met the inclusion criteria. Asthma was reported in 4276 (12.6%). The main comorbidities among asthmatic patients were obesity (23.1%), hypertension (12.7%) and diabetes (4.5%). As compared with non-asthmatic patients, asthmatic patients were more often female (70.0 versus 62.1%, p<0.001), of younger age (42.2 versus 43.8 years, p<0.001) and obese (23.1 versus 17.6%, p<0.001). The rate of hospitalisation did not differ significantly (4.7 versus 4.2%, p=0.203) and no asthmatic patient died during follow-up ( versus 25 non-asthmatic patients, 0.1%; p=0.109). In multivariate analysis, asthma was independently associated with higher risk of clinical worsening (OR 1.23, 95% CI 1.04-1.44, p=0.013)., Conclusion: In a large French cohort of patients receiving initial ambulatory care and home monitoring for COVID-19, asthma was independently associated with higher risk of clinical worsening although no asthmatic patient died within the 30 days follow-up., Competing Interests: Conflict of interest: A. Beurnier reports personal fees from AstraZeneca and personal fees from Sanofi, outside the submitted work. Conflict of interest: Y. Yordanov has nothing to disclose. Conflict of interest: A. Dechartres has nothing to disclose. Conflict of interest: A. Dinh has nothing to disclose. Conflict of interest: E. Debuc has nothing to disclose. Conflict of interest: F-X. Lescure has nothing to disclose. Conflict of interest: P. Jourdain has nothing to disclose. Conflict of interest: L. Jaulmes have nothing to disclose. Conflict of interest: M. Humbert reports personal fees and nonfinancial support from GlaxoSmithKline, and personal fees from AstraZeneca, Novartis, Sanofi and Chiesi, outside the submitted work., (Copyright ©The authors 2022.)

This article describes a case of healthcare-associated monkeypox infection in France during the 2022 outbreak. A female medical resident accidently pricked herself with a soiled subcutaneous needle used to harvest a vesicle of a patient infected by monkeypox virus and developed 4 days later a unique skin lesion, positive for monkeypox virus., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW)., Methods: A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed., Results: The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained., Conclusions: Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries., (© 2022. The Author(s).)

Background: Community health care accounts for the vast majority of antibiotic use in Europe. Given the threat of antimicrobial resistance (AMR), there is an urgent need to develop new antimicrobial stewardship (AMS) interventions in primary care that could involve different health care providers, including community pharmacists., Objectives: This study aimed to explore the perceptions, currents practices, and interventions of community pharmacists regarding AMS., Methods: Semistructured qualitative interviews were conducted with community pharmacists in France. Participants were recruited through a professional organization of community pharmacists combined with a snowballing technique. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. The Consolidated Framework for Implementation Research was used while developing the interview guide and carrying out thematic analysis., Results: Sixteen community pharmacists participated. All the respondents had good awareness about antimicrobial resistance and believed that community pharmacists had an important role in tackling AMR. Some barriers to community pharmacists' participation in AMS were identified such as difficult interactions with prescribers, lack of time, and lack of access to patient medical records and diagnosis. Increased patient education, audits and feedback of antibiotic prescribing, increased point-of-care testing, and delayed prescribing were interventions suggested by the pharmacists to improve antibiotic use in primary care. Strategies cited by participants to facilitate the implementation of such interventions are increased pharmacist-general practitioner collaboration, specialized training, clinical decision support tools, and financial incentives., Conclusion: This study suggests that community pharmacists could play a greater role in infection management and AMS interventions. Further interprofessional collaboration is needed to optimize antibiotic prescribing and utilization in community health care., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Healthcare services across the world have been deeply impacted by the COVID-19 pandemic. In primary care, community pharmacists have had an important role in the frontline healthcare response to the pandemic., Objectives: This study aimed to explore the experiences, contributions and perceived challenges of community pharmacists regarding the provision of healthcare services during the COVID-19 pandemic., Methods: Semi-structured qualitative interviews were conducted with community pharmacists in France. Participants were recruited through a professional organization of pharmacists combined with a snowballing technique. Interviews were transcribed and then analyzed using thematic analysis., Results: A total of 16 community pharmacists participated in the interviews. Study participants described providing a range of novel services in response to the pandemic on top of continuing their usual services. All participants described providing preventative services to reduce and mitigate the spread of SARS-CoV-2, such as education on hygiene and social distancing, delivery of face masks and hand sanitizer and adjusting pharmacy premises. Most respondents also described being involved in SARS-CoV-2 detection through screening and performing antigen testing in pharmacies. Participants reported being actively involved in COVID-19 vaccination by educating the general public about vaccines, facilitating their distribution to general practitioners as well as administering vaccines. Over half the respondents described rapidly changing guidelines and service users' anxiety as challenges to the provision of healthcare services during the pandemic., Conclusions: This study suggests that community pharmacists have significantly contributed to the response to the COVID-19 pandemic by ensuring continuity of pharmaceutical services and providing novel screening, testing and vaccination services. Their roles and responsibilities during the COVID-19 health crisis indicate that they can play an important role in the management of emerging infectious diseases., (© 2022. The Author(s).)

Background: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France., Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease., Results: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72])., Conclusion: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19., (© 2022. The Author(s).)

Objectives: During the COVID-19 pandemic, antibiotic use was very common. However, bacterial co-/secondary infections with coronaviruses remain largely unknown in standard wards. We aimed to investigate the characteristics of pulmonary bacterial infections associated with COVID-19 in hospitalized patients., Methods: A retrospective monocentric observational study was conducted in Bichat hospital, France, between February 26 and April 22, 2020. All patients hospitalized in standard wards with COVID-19 (positive nasopharyngeal PCR and/or typical aspect on CT-scan) and diagnosed with pulmonary bacterial infection (positive bacteriological samples) were included. Bacteriological and clinical data were collected from the microbiology laboratories and patient's medical records., Results: Twenty-three bacteriological samples from 22 patients were positive out of 2075 screened samples (1.1%) from 784 patients (2.8%). Bacterial infection occurred within a median of 10 days after COVID-19 onset. Diagnosis of pulmonary bacterial infection was suspected on increase of oxygen requirements (20/22), productive cough or modification of sputum aspect (17/22), or fever (10/22). Positive samples included 13 sputum cultures, one FilmArray® assay on sputum samples, one bronchoalveolar lavage, six blood cultures, and two pneumococcal urinary antigen tests. The most frequent bacteria were Pseudomonas aeruginosa (6/23), Staphylococcus aureus (5/23), Streptococcus pneumoniae (4/23), Enterococcus faecalis (3/23), and Klebsiella aerogenes (3/23). No Legionella urinary antigen test was positive. Four out of 496 nasopharyngeal PCR tests (0.8%) were positive for intracellular bacteria (two Bordetella pertussis and two Mycoplasma pneumonia)., Conclusions: Pulmonary bacterial secondary infections and co-infections with SARS-CoV-2 are uncommon. Antibiotic use should remain limited in the management of COVID-19., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Bone and joint infections (BJIs) are complex infections that require precise microbiological documentation to optimize antibiotic therapy. Currently, diagnosis is based on microbiological culture, sometimes complemented by amplification and sequencing of the 16S rDNA gene. Clinical metagenomics (CMg), that is, the sequencing of the entire nucleic acids in a sample, was previously shown to identify bacteria not detected by conventional methods, but its actual contribution to the diagnosis remains to be assessed, especially with regard to 16S rDNA sequencing. In the present study, we tested the performance of CMg in 34 patients (94 samples) with suspected BJIs, as compared to culture and 16S rDNA sequencing. A total of 94 samples from 34 patients with suspicion of BJIs, recruited from two sites, were analyzed by (i) conventional culture, (ii) 16S rDNA sequencing (Sanger method), and (iii) CMg (Illumina Technology). Two negative controls were also sequenced by CMg for contamination assessment. Based on the sequencing results of negative controls, 414 out of 539 (76.7%) bacterial species detected by CMg were considered as contaminants and 125 (23.2%) as truly present. For monomicrobial infections (13 patients), the sensitivity of CMg was 83.3% as compared to culture, and 100% as compared to 16S rDNA. For polymicrobial infections (13 patients), the sensitivity of CMg was 50% compared to culture, and 100% compared to 16S rDNA. For samples negative in culture (8 patients, 21 samples), CMg detected 11 bacteria in 10 samples from 5 different patients. In 5/34 patients, CMg brought a microbiological diagnosis where conventional methods failed, and in 16/34 patients, CMg provided additional information. Finally, 99 antibiotic resistance genes were detected in 24 patients (56 samples). Provided sufficient genome coverage (87.5%), a correct inference of antibiotic susceptibility was achieved in 8/8 bacteria (100%). In conclusion, our study demonstrated that the CMg provides complementary and potentially valuable data to conventional methods of BJIs diagnosis., Competing Interests: GGu and GGe were employed by bioMérieux SA. SF was employed by Genoscreen. ER received consulting fees from Illumina and Pathoquest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 d’Humières, Gaïa, Gueye, de Lastours, Leflon-Guibout, Maataoui, Duprilot, Lecronier, Rousseau, Gamany, Lescure, Senard, Deconinck, Dollat, Isernia, Le Hur, Petitjean, Nazimoudine, Le Gac, Chalal, Ferreira, Lazarevic, Guigon, Gervasi, Armand-Lefèvre, Schrenzel and Ruppé.)

Drug-resistant tuberculosis (DR-TB) is a major public health concern worldwide. The prolonged isolation required is a source of challenges for both healthcare workers and patients, especially in high-income countries where DR-TB patients are frequently migrants with vulnerabilities. However, data on the needs of these vulnerable patients are scarce. Our objective was to identify and quantify conflict or inappropriate care situations experienced by both DR-TB patients and healthcare workers. This 10-year retrospective observational study (01/2008 to 10/2018) was conducted in a referral center for resistant tuberculosis management in Paris, France. Sixty-five DR-TB patients were hospitalized during the study period. Their demographic, clinical and social characteristics and any conflict or inappropriate care situations they experienced with healthcare workers while hospitalized were analyzed. Conflict or inappropriate care situations with healthcare workers were reported for 24 patients during their stay (36.9%). Eleven patients (16.9%) had difficulty adhering to respiratory isolation rules, 15 (23.1%) were discharged against medical advice, 9 (13.8%) were excluded from hospital for disciplinary reasons, verbal or physical violence was reported for 7 patients (10.8%), and 4 arrests (6.2%) were made by the police. Conflict situations were reported more often when there was a language barrier (70.8%, p<0.0001). More than one-third of patients with DR-TB in this referral center experienced at least one inappropriate care situation with healthcare workers. This study illustrates the urgent need to promote a patient-centered approach and to respond to the challenges of its practical implementation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kherabi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical decision support systems (CDSSs) are increasingly being used by clinicians to support antibiotic decision making in infection management. However, coexisting CDSSs often target different types of physicians, infectious situations, and patient profiles. The objective of this study was to perform an up-to-date inventory of French language CDSSs currently used in community and hospital settings for antimicrobial prescribing and to describe their main characteristics. A literature search, a search among smartphone application stores, and an open discussion with antimicrobial stewardship (AMS) experts were conducted in order to identify available French language CDSSs. Any clinical decision support tool that provides a personalized recommendation based on a clinical situation and/or a patient was included. Eleven CDSSs were identified through the search strategy. Of the 11 CDSSs, only 2 had been the subject of published studies, while 9 CDSSs were identified through smartphone application stores and expert knowledge. The majority of CDSSs were available free of charge ( n = 8/11, 73%). Most CDSSs were accessible via smartphone applications ( n = 9/11, 82%) and online websites ( n = 8/11, 73%). Recommendations for antibiotic prescribing in urinary tract infections, upper and lower respiratory tract infections, and digestive tract infections were provided by over 90% of the CDSSs. More than 90% of the CDSSs displayed recommendations for antibiotic selection, prioritization, dosage, duration, route of administration, and alternative antibiotics in case of allergy. Information about antibiotic side effects, prescription recommendations for specific patient profiles and adaptation to local epidemiology were often missing or incomplete. There is a significant but heterogeneous offer for antibiotic prescribing decision support in French language. Standardized evaluation of these systems is needed to assess their impact on antimicrobial prescribing and antimicrobial resistance.

Background: Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care., Objectives: To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs., Methods: We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections., Results: We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001)., Conclusions: CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant., Methods: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown., Results: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006)., Conclusion: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13 low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DR low downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options., (© 2022. The Author(s).)

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support., Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely., Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms., Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Chagas disease is a debilitating and often fatal pathology resulting from infection by the protozoan parasite Trypanosoma cruzi . In its recommendations, the World Health Organization states that the diagnosis of T. cruzi infection is usually based on the detection of antibodies against T. cruzi antigens and performed with two methodologically different assays. An inconclusive result can be resolved with a third "confirmatory" assay. The objective of this article is to evaluate the effectiveness of the Chagas Western Blot IgG assay (LDBio Diagnostics, Lyon, France) as a confirmatory serologic test. The Chagas Western Blot IgG assay was performed with native antigens derived from a T. cruzi strain of the TcVI genotype. Retrospective sera were provided by two parasitology laboratories (France and Argentina). The sensitivity, specificity, positive predictive value and negative predictive value of the Chagas blot were all 100% in our sera collection. The Chagas blot is an easy and qualitative method for the diagnosis of Chagas disease, with results in less than 2 h. This immunoblot has potential as a supplemental test for the confirmation of the presence of antibodies against T. cruzi in serum specimens. Nonetheless, the very good initial results presented here will need to be confirmed in larger studies.

Background: The first wave of the COVID-19 pandemic confronted healthcare systems around the world with unprecedented organizational challenges, particularly regarding the availability of intensive care unit (ICU) beds. One strategy implemented in France to alleviate healthcare pressure during the first COVID-19 wave was inter-hospital transfers of selected ICU patients from overwhelmed areas towards less saturated ones. At the time, the impact of this transfer strategy on patient mortality was unknown. We aimed to compare in-hospital mortality rates among ICU patients with COVID-19 who were transferred to another healthcare facility and those who remained in the hospital where they were initially admitted to., Method: A prospective observational study was performed from 1 March to 21 June 2020. Data regarding hospitalized patients with COVID-19 were collected from the Ministry of Health-affiliated national SI-VIC registry. The primary endpoint was in-hospital mortality., Results: In total, 93,351 hospital admissions of COVID-19 patients were registered, of which 18,348 (19.6%) were ICU admissions. Transferred patients (n = 2228) had a lower mortality rate than their non-transferred counterparts (n = 15,303), and the risk decreased with increasing transfer distance (odds ratio (OR) 0.7, 95% CI: 0.6-0.9, p = 0.001 for transfers between 10 and 50 km, and OR 0.3, 95% CI: 0.2-0.4, p < 0.0001 for transfer distance > 200 km). Mortality decreased overall over the 3-month study period., Conclusions: Our study shows that the mortality rates were lower for patients with severe COVID-19 who were transferred between ICUs across regions, or internationally, during the first pandemic wave in France. However, the global mortality rate declined overall during the study. Transferring selected patients with COVID-19 from overwhelmed regions to areas with greater capacity may have improved patient access to ICU care, without compounding the short-term mortality risk of transferred patients., (© 2021. The Author(s).)

Background: Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear., Objectives: To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment., Methods: From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B)., Results: 474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS <1 day (63% versus 60%, P = 0.57) and ED antibiotic prescription (59% versus 58%, P = 0.92) were not significantly different. Patients in the POCT arm were more frequently assigned a single room when having a positive PCR for influenza, respiratory syncytial virus and metapneumovirus [52/70 (74%) versus 19/38 (50%) in the central testing arm, P = 0.012]., Conclusions: Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: The efficacy of lockdown in containing the COVID-19 pandemic has been reported in different studies. However, the impact on sociodemographic characteristics of individuals infected with SARS-CoV-2 has not been evaluated. The aim of this study was to describe the changes in sociodemographic characteristics of patients hospitalized for COVID-19 and to compare the transmission risk factors of COVID-19 before and during lockdown in France., Methods: An observational retrospective study was conducted in a University Hospital in Paris, France. Data from patients hospitalized for COVID-19 in the Infectious Diseases Department between February 26 and May 11, 2020 were collected. The study population was divided into 2 groups: group A of patients infected before lockdown, and group B of patients infected during lockdown, considering a maximum incubation period of 14 days. Sociodemographic characteristics and transmission risk factors were compared between the 2 groups using Student's t-test for continuous variables and Chi-2 test or Fisher exact test for categorical variables., Results: Three hundred eighty-three patients were included in the study, 305 (79.6%) in group A and 78 (20.4%) in group B. Patients in group A were significantly younger (60.0 versus (vs) 66.5 years (p = 0.03)). The professionally active population was larger in group A (44.3% vs 24.4%). There were significantly more non-French-speaking people in group B (16.7% vs 6.6%, p <  0.01). Most patients from group A had individual accommodation (92.8% vs 74.4%, p <  0.01). Contact with a relative was the main transmission risk factor in both groups (24.6% vs 33.3%, p = 0.16). Recent travel and large gathering were found only in group A. The proportion of people living in disadvantaged conditions, such as homeless people or people living in social housing, was significantly higher in group B (11.5% vs 4.3%, p = 0.03) as was the proportion of institutionalized individuals (14.1% vs 3.0%, p <  0.01)., Conclusions: In this study conducted in patients hospitalized for COVID-19 in Paris, France, the likelihood of being infected despite the lockdown was higher for people who do not speak French, live in social housing, are homeless or institutionalized. Targeted measures have to be implemented to protect these populations., (© 2021. The Author(s).)

Objectives: Studies on coronavirus disease 2019 (COVID-19) have mainly focused on hospitalized patients or those with severe disease. We aim to assess the clinical characteristics, outcomes and factors associated with hospital admission or death in adult outpatients with COVID-19., Methods: This is a prospective cohort of outpatients with suspected or confirmed COVID-19, registered in the Covidom telesurveillance solution for home monitoring of patients with COVID-19 in the Greater Paris area, from March to August 2020. The primary outcome was clinical worsening, defined as hospitalization or death within 1 month after symptom onset., Results: Among 43 103 patients, mean age was 42.9 years (SD 14.3 years); 93.0% (n = 40 081) of patients were <65 years old and 61.9% (n = 26 688) were women. Of these 43 103 patients, 67.5% (n = 29 104) completed a medical questionnaire on co-morbidities and symptoms. The main reported co-morbidities were asthma (12.8%; n = 3685), hypertension (12.3%; n = 3546) and diabetes (4.8%; n = 1385). A small proportion of all eligible patients (4.1%, 95% CI 3.9-4.2; 1751/43 103) experienced clinical worsening. The rate of hospitalization was 4.0% (95% CI 3.8%-4.2%; n = 1728) and 0.1% (95% CI 0.1%-0.2%; n = 64) died. Factors associated with clinical worsening were male sex, older age, obesity and co-morbidities such as chronic renal disease or cancer under treatment. Probability of worsening was reduced with anosmia/ageusia., Conclusions: Clinical worsening was rare among outpatients. Male sex, older age and co-morbidities such as chronic renal disease, active cancers or obesity were independently associated with clinical worsening. However, our cohort may include patients younger and healthier than the general population., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen., Methods: We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting., Results: Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83-90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46-0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68-1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group., Conclusions: Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Lung function in survivors of SARS-Co-V2 pneumonia is poorly known, but concern over the possibility of sequelae exists., Methods: Retrospective study on survivors with confirmed infection and pneumonia on chest-CT. Correlations between PFT and residual radiologic anomalies at three months taking into account initial clinical and radiological severity and steroid use during acute phase., Results: 137 patients (69 men, median age 59 (Q1 50; Q3 68), BMI 27.5 kg/m 2 (25.1; 31.7)) were assessed. Only 32.9% had normal PFT, 75 had altered DLCO. Median (Q1; Q3) values were: VC 79 (66; 92) % pred, FEV1 81 (68; 89), TLC 78 (67; 85), DLCO 60 (44; 72), and KCO 89 (77; 105). Ground glass opacities (GGO) were present in 103 patients (75%), reticulations in 42 (30%), and fibrosis in 18 (13%). There were significantly lower FEV1 (p = 0.0089), FVC (p = 0.0010), TLC (p < 0.0001) and DLCO (p < 0.0001) for patients with GGO, lower TLC (p = 0.0913) and DLCO (p = 0.0181) between patients with reticulations and lower FVC (p = 0.0618), TLC (p = 0.0742) DLCO (p = 0.002) and KCO (p = 0.0114) between patients with fibrosis. Patients with initial ≥50% lung involvement had significantly lower FEV1 (p = 0.0019), FVC (p = 0.0033), TLC (p = 0.0028) and DLCO (p = 0.0003) compared to patients with ≤10%. There was no difference in PFT and residual CT lesions between patients who received steroids and those who did not., Conclusion: The majority of patients have altered PFT at three months, even in patients with mild initial disease, with significantly lower function in patients with residual CT lesions. Steroids do not seem to modify functional and radiological recovery. Long-term follow-up is needed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2., Methods: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by multiplex PCR if they presented ILI symptoms., Results: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2-positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (P = .013) and headaches (P = .048), than single SARS-CoV-2 infections., Conclusions: SARS-CoV-2-infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Guidelines for stopping coronavirus disease 2019 patient isolation are mainly symptom-based, with isolation for 10 to 20 days depending on their condition., Methods: In this study, we describe 3 deeply immunocompromised patients, each with different clinical evolutions. We observed (1) the patients' epidemiological, clinical, and serological data, (2) infectiousness using viral culture, and (3) viral mutations accumulated over time., Results: Asymptomatic carriage, symptom resolution, or superinfection with a second severe acute respiratory syndrome coronavirus 2 strain were observed, all leading to prolonged infectious viral shedding for several months., Conclusions: Understanding underlying mechanisms and frequency of prolonged infectiousness is crucial to adapt current guidelines and strengthen the use of systematic polymerase chain reaction testing before stopping isolation in immunocompromised populations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)