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Doravirine (DOR) efficacy and safety have been evaluated in adult naive or treated patients starting a DOR-based regimen between September 15, 2019, and December 31, 2020. Medical history and examination, laboratory results, and tolerance were assessed during the 48 weeks of follow-up. Among the 77 patients included, virological control (VC) was noticed for 66 patients at baseline. Median age was 51 years, and 62% were men. The most common reason for initiating a DOR-based therapy was toxicity (44; 67%) and, especially, weight gain. A virological suppression (VS) was maintained in 55 (83%) patients of the VC group and noticed in 9 (82%) of the non-VC patients at week 48, by intention-to-treat analysis. On treatment analysis, 98% and 100% patients achieved VS in the VC and non-VC groups, respectively. The renal and metabolic tolerance were good. DOR-based regimens appear to be a safe and relevant strategy to circumvent drug interactions and drugs with a poor metabolic tolerance profile.

OBJECTIVES: Although menopausal hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms of menopause, its association with the development of arterial hypertension remains unclear. We sought to explore associations between different formulations of MHT and incident hypertension among menopausal women in a prospective cohort study. METHODS: We used the Etude Epidemiologique de femmes de la Mutuelle Generale de l'Education (E3N) cohort, a French prospective population-based study initiated in 1990 on 98,995 women. Out of these, 49,905 menopausal women with complete information on the use of MHT, and without prevalent hypertension at inclusion were included. RESULTS: The mean age of the population at baseline was 54.2 ±â€Š4.3 years, and 32,183 (64.5%) reported ever using MHT. Among these women, 10,173 cases of incident hypertension were identified over an average follow-up time of 10.6 years. Compared with women who never used MHT, those who ever used it had an increased risk of incident hypertension (adjusted HR 1.07, 95% CI 1.02-1.12) after adjustment for body mass index and other potential confounders. Oral but not transdermal estrogen use was associated with an increased risk of hypertension (adjusted HR = 1.09; 95% CI: 1.04-1.14 and HR = 1.03; 95% CI: 0.99-1.07, respectively). However, the HRs associated with oral and transdermal estrogens did not differ significantly (P-homogeneity = 0.09). Regarding the role of concomitant progestogens, pregnane and norpregnane derivatives were significantly associated with hypertension risk (HR = 1.12; 95% CI: 1.06-1.19 and HR = 1.06; 95% CI: 1.01-1.13, respectively). CONCLUSIONS: MHT was associated with a modest but significant increased risk of incident hypertension, especially when using oral estrogen in combination with a progestogen such as pregnane and norpregnane derivatives. Surveillance of blood pressure should be added to the medical surveillance of MHT users.Video Summary:http://links.lww.com/MENO/A802.

Social contact patterns might contribute to excess burden of tuberculosis in men. We conducted a study of social contact surveys to evaluate contact patterns relevant to tuberculosis transmission. Available data describe 21 surveys in 17 countries and show profound differences in sex-based and age-based patterns of contact. Adults reported more adult contacts than children. Children preferentially mixed with women in all surveys (median sex assortativity 58%, interquartile range [IQR] 57%–59% for boys, 61% [IQR 60%–63%] for girls). Men and women reported sex-assortative mixing in 80% and 95% of surveys (median sex assortativity 56% [IQR 54%–58%] for men, 59% [IQR 57%–63%] for women). Sex-specific patterns of contact with adults were similar at home and outside the home for children; adults reported greater sex assortativity outside the home in most surveys. Sex assortativity in adult contacts likely contributes to sex disparities in adult tuberculosis burden by amplifying incidence among men.

BackgroundThe diffusion of the SARS-CoV-2 delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status.MethodsWe retrospectively analysed data from patients hospitalised in 10 centres with a SARS-CoV-2 infection (delta variant) from July to November 2021: i) all patients who had completed their primary vaccination at least 14 days before hospital admission; and ii) the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression.FindingsWe included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older, more frequently males, and with more comorbidities. They were less often admitted for Covid-19 (59·3% vs. 75·1%, pConclusionsAmong patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Background Since the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada. Methods CONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 - February 2021), using the same methodology for both periods. We recruited participants by random digit dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance

BACKGROUND 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. OBJECTIVE The objective of this study was to perform an up-to-date inventory of French-language clinical decision support systems (CDSSs) currently used in community and hospital settings for antimicrobial prescribing and to describe their main characteristics. METHODS A literature search, a search among mobile application stores and an open discussion with antimicrobial stewardship (AMS) experts were conducted in order to identify all French-language CDSSs available. Any clinical decision support tool that provides a personalized recommendation based on a clinical situation and/or a patient was included. A data collection form was developed and reviewed by infectious disease and AMS specialists. Collected data included the CDSS characteristics regarding administration, access, targeted users and patients, search criteria and type of information provided. RESULTS Eleven CDSSs were identified through the search strategy. Most CDSSs were designed on a regional scale by multidisciplinary teams and were intended for both inpatient and outpatient care. The majority of CDSSs were available free of charge (n=8/11, 73%). Only 2 CDSSs were designed exclusively for ambulatory care. 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. Recommendations for the treatment of cardiovascular infections, bloodstream infections and central venous catheter-related infections were advised by less than half of the CDSSs. More than 90% of the CDSSs displayed recommendations for antibiotic selection, prioritization, dosage, duration, route of administration and alternatives in case of allergy. Information about antibiotic side effects, prescribing recommendations for specific patient profiles and adaptation to local epidemiology were often missing or incomplete. CONCLUSIONS There is a significant but heterogeneous offer for antibiotic prescribing decision support. Standardized evaluation of these systems is needed to assess their impact on antimicrobial prescribing and antimicrobial resistance.

SynopsisObjectivesThe extended half-life of dalbavancin justifies a once-a-week dosing schedule and is supposed to favour early discharge. These advantages may therefore compensate for the cost of dalbavancin. We aimed to assess the real-life budget impact of dalbavancin through its impact on the length of stay in French hospitals.MethodsA multicentre cohort based on the French registry of dalbavancin use in 2019 was compared to the French national discharge summary database. Lengths of stay and budget impact related to the infection type, the time of introduction of dalbavancin, the type of catheter and patient subgroups were assessed. An early switch was defined when dalbavancin was administered as the first or second treatment and within less than 11 days of hospitalization.ResultsOne hundred seventy-nine patients were identified in the registry, and 154 were included in our study. Dalbavancin is mostly used for bone and joint infections, infective endocarditis and acute bacterial skin and skin structure infections. When compared to the data for similar patients in the national database, the length of stay was almost always shorter for patients treated with dalbavancin. The budget impact for dalbavancin was heterogeneous but frequently generated savings. Early switching was associated with savings (or lesser costs). Patients who required a deep venous catheter and those with the most severe patients benefited the most from dalbavancin.ConclusionsOur study confirms that dalbavancin is associated with early discharge, which can offset its cost and generate savings. The greatest benefit is achieved with an early switch.

To compare the rate of posterior synechiae of the iris (PSI) occurrence after phacovitrectomy between a group with lens-in-the-bag (LIB) implantation, that is, implantation in the capsular bag, and a group with bag-in-the-lens (BIL) implantation.CHU de Caen, Department of Ophthalmology, Caen, France.Comparative retrospective study.One hundred consecutive cases of phacovitrectomies conducted between May 2013 and July 2016 were included. A retrospective analysis of the occurrence rate of PSI in the LIB group and in the BIL group was performed, using multivariate analysis including multiple risk factors such as preoperative synechiae, proliferative diabetic retinopathy, use of 20-gauge vitrectomy, use of gas or silicone tamponade, and use of endophotocoagulation.One hundred eyes of 92 patients were included in this study (55 eyes in the LIB group and 45 in the BIL group). The occurrence of PSI was significantly lower in the BIL group with 1 case (2%) versus 22 cases (40%) in the LIB group (P .001). Among the risk factors studied, preoperative synechiae and the use of retinal endophotocoagulation were almost significantly associated with the occurrence of PSI (P = .068 and P = .087, respectively). In the LIB group, these PSI led to 1 case of acute elevation of intraocular pressure by pupillary seclusion and the use of laser iridotomy in 8 cases.The use of BIL rather than LIB implantation in phacovitrectomy practically eliminates PSI.

International audience; PURPOSE: Giving advice about antibiotic prescription through dedicated consultations is a cornerstone of antibiotic stewardship programmes. Our objective was to explore practices, organisation, and regulatory requirements related to antibiotic advising.METHODS: We performed an international, exploratory, Internet-based, cross-sectional survey targeting infectious diseases and clinical microbiology specialists. It was disseminated through ESCMID and ESGAP networks.RESULTS: Answers from 830 participants (74 countries, 77% of participants from Europe) were collected. Consultations were mostly given on demand (81%, 619/764), while unsolicited consultations targeting specific conditions (e.g., positive blood culture) were less frequent (66%, 501/764). Consultations usually included indications on diagnostic work-up and follow-up (> 79%). Curbside consultations (i.e., without examining the patient) were reported by 82% (598/733) of respondents, mainly by phone (89%, 531/598). The referring physician was considered authorised not to follow the advice by 57% (383/676). Direct consultations (i.e., after examining the patient) were recorded in the medical file more frequently than curbside consultations (69%, 472/689 vs 35%, 206/592). Concerning legal liability, the majority of respondents considered that it is shared between the adviser and the referring physician, who, however, is considered primarily responsible. The advisers' liability was considered to be lower in cases of curbside and unrecorded consultations. Significant inter-countries and intra-country variability were identified, suggesting that the setting markedly influenced practices.CONCLUSION: Significant variability exists in the practice of antibiotic advising. This concerns both the organisation of care and how advisers perceive regulatory requirements. These elements must be taken into account when implementing antibiotic stewardship programmes and when training stewards.

Background Many countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity. Aim We aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours. Methods We conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020. Result Among the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%. Conclusion The lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

International audience

In the first trimester 2020, a significant number of countries implemented general lockdowns of their populations to contain the quickly expanding SARS-CoV-2 epidemic and avoid major saturation of health care capacity. Understanding how these unprecedented measures impacted population behaviour and contact patterns is key to predict more accurately the health, social and economic impacts of such extreme actions if they were to be applied to future outbreaks. We set up an online survey to measure how the lockdown affected social contact patterns in France, and collected information from 42,036 participants aged 18 years and over between April 10 and April 28, 2020. Among the participants who normally worked outside home prior to the lockdown (72% of the survey population), 68% reported that they had moved to working from home and 17% reported being unemployed during the lockdown.Only 2% of participants used public transport during lockdown, as opposed to 37% before it. Participants reported increased frequency of washing hands, switch in greeting behaviour, but generally limited use of masks outside home. 138,934 contacts were reported, with an average 3.3 contacts per individual per day (1.7 for individuals aged >65 years old compared to 3.6 for younger age-groups). This represented a 70% reduction compared with previous surveys, consistent with reductions in transmission rates measured during the lockdown. Contacts in workplaces, shops, and transports on the previous day were respectively reported in only 11%, 31% and 0.5% of the participants. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%. This study shows that the lockdown dramatically affected population’s behavior, work, risk perception and contact patterns. Both frequency and heterogeneity of contacts were affected, impacting potential important features of virus dissemination. Such surveys are essential to evaluate more accurately the impact of past or future lockdowns and anticipate epidemic dynamics in these conditions.

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p

Infection transmission is a complex and dynamic process, and is therefore difficult to assess. Consequently, mathematical models are a useful tool to understand any leverage on this transmission, such as vaccination. Models can provide guidance to implement an optimal vaccination campaign whether it concerns the fraction of the population or the age-group to be vaccinated. Mathematical models can also provide insights on counter-intuitive collateral effects of vaccination campaign, given the possibility that the overall benefits for the general population may hide deleterious effects on some sub-groups. As a large proportion of the population is now vaccinated, complex modelling taking into account individual and population heterogeneity and behaviour is necessary although challenging. But the most crucial aspect in the future of mathematical modelling still consists in obtaining precise and exhaustive data.

International audience; Objectives:To investigate fear of legal claims and defensive behaviours among specialists in infectious diseases (ID) and clinical microbiology (CM) and to identify associated demographic and professional characteristics.Methods:AntibioLegalMap was an international cross-sectional internet-based survey targeting specialists in ID and CM. Three variables were explored: fear of legal liability in antibiotic prescribing/advising on antibiotic prescription; defensive behaviours in antibiotic prescribing; and defensive behaviours in advising. A multivariable logistic regression analysis was performed to identify factors significantly associated with each of the three variables.Results:Eight hundred and thirty individuals from 74 countries participated. Only 0.4% (3/779) had any kind of condemnation for malpractice related to antibiotic prescription. Concerning the fear of liability, 21.2% (164/774) of respondents said they never worried, 45.1% (349/774) sometimes worried and 28.6% (221/774) frequently worried when prescribing/advising on antibiotic prescription. Being female, younger than or equal to 35 years and aware of previous cases of litigation were independently associated with fear. Most respondents (85.0%, 525/618) reported some defensive behaviour in antibiotic prescribing. These behaviours were independently associated with being younger than or equal to 35 years and sometimes or often worried about liability. Similarly, 76.4% (505/661) reported defensive behaviours in advising. These behaviours were associated with being sometimes or often worried about liability. The preferred measures to reduce fear and defensive behaviours were having local guidelines and sharing decisions through teamwork.Conclusions:A significant proportion of specialists in ID and CM reported some form of defensive behaviour in prescribing or advising to prescribe antibiotics. Defensive medicine should be considered when implementing antibiotic stewardship programmes.

Background Postgraduate training has the potential to shape the prescribing practices of young doctors. Objectives To investigate the practices, attitudes and beliefs on antibiotic use and resistance in young doctors of different specialties. Methods We performed an international web-based exploratory survey. Principal component analysis (PCA) and bivariate and multivariate [analysis of variance (ANOVA)] analyses were used to investigate differences between young doctors according to their country of specialization, specialty, year of training and gender. Results Of the 2366 participants from France, Greece, Italy, Portugal, Slovenia and Spain, 54.2% of young doctors prescribed antibiotics predominantly as instructed by a mentor. Associations between the variability of answers and the country of training were observed across most questions, followed by variability according to the specialty. Very few differences were associated with the year of training and gender. PCA revealed five dimensions of antibiotic prescribing culture: self-assessment of knowledge, consideration of side effects, perception of prescription patterns, consideration of patient sickness and perception of antibiotic resistance. Only the country of specialization (partial η2 0.010–0.111) and the type of specialization (0.013–0.032) had a significant effect on all five identified dimensions (P Conclusions The country of specialization followed by the type of specialization are the most important determinants of young doctors’ perspectives on antibiotic use and resistance. The inclusion of competencies in antibiotic use in all specialty curricula and international harmonization of training should be considered.

International audience; OBJECTIVE: To compare the practices of French infection specialists related to antibiotic therapy duration between 2016 and 2018.METHODS: We conducted two identical surveys (in 2016 and 2018) targeting hospital-based infection specialists (medical physicians, pharmacists) who gave at least weekly advice on antibiotic prescriptions. The questionnaire included 15 clinical vignettes. Part A asked about the durations of antibiotic therapies they would usually advise to prescribers, and part B asked about the shortest duration they would be willing to advise for the same clinical situations.RESULTS: We included 325 specialists (165 in 2016 and 160 in 2018), mostly infectious disease specialists (82.4%, 268/325), members of antibiotic stewardship teams in 72% (234/325) of cases. Shorter antibiotic treatments (as compared with the literature) were advised to prescribers in more than half of the vignettes by 71% (105/147) of respondents in 2018, versus 46% (69/150) in 2016 (P

International audience; Objectives - We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).Methods - Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords 'prosthetic joint', and 'tuberculosis'. Results - During years 1997-2016, 13 patients (8 males, 5 females, median age 79 years [range, 60-86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4-20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6-32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS). Conclusions - M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.

Objective To provide an epidemiologic description of Kikuchi-Fujimoto disease (KFD), and to describe its relationship with systemic lupus erythematosus (SLE) in a population of sub-Saharan origin. Methods Patients were retrospectively included on the basis of lymph node histology compatible with KFD reported in Martinique from 1991 until 2013. In order to describe the characteristics of the disease in a larger cohort, we subsequently included more patients of Afro-Caribbean origin from Guadeloupe and French Guiana. Results In Martinique, mean annual incidence between 1991 and 2013 was 2.78 cases for 1 million inhabitants (95% confidence interval 1.73-3.93). A total of 36 Afro-Caribbean patients from the 3 French American regions were included. Mean age was 30.5 years (range 5-59 years) and the female:male ratio was 3:1. The main characteristics were cervical adenopathies (88.8%), fever (83.3%), asthenia (73.0%), weight loss (64.4%), and recurrence in 33.3%. KFD was associated with lupus (n = 9 for SLE, n = 2 for cutaneous lupus) in 36.6% (11 of 30). Conclusion We report the first epidemiologic description of KFD in a population of sub-Saharan origin. According to our data, this disease is present in the black African diaspora and is strongly associated with autoimmune diseases, particularly lupus.

Supported by a travel grant to JD from the Association pour la Recherche et l'Enseignement en Nephrologie Poitou-Charentes, which had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

Introduction Le vieillissement des personnes vivant avec le VIH (PVVIH) sous antiretroviraux (ARV) (antiretroviraux) expose aux comorbidites et donc aux co-medications, avec un risque d’interactions medicamenteuses souvent meconnu par les medecins. L’objectif etait d’evaluer les traitements associes aux ARV et les interactions possibles decouvertes lors d’une consultation de suivi par un infectiologue. Materiels et methodes Etude observationnelle transversale multicentrique nationale realisee chez les PVVIH consecutifs sous traitement ARV consultant de maniere programmee un infectiologue durant la semaine du 10 au 16 decembre 2019. Le recueil des donnees a ete etabli via un questionnaire standardise informatise rempli par le medecin et decrivant les traitements connus anterieurement ou decouvert pendant la consultation. L’analyse des interactions medicamenteuses entre les ARV et les autres traitements a ete evaluee et la proportion de modification therapeutique mesuree. Resultats Vingt-deux centres ont participe a cette etude permettant d’interroger 496 PVVIH. Les ARV comprenaient un inhibiteur d’integrase dans 60,9 % (n = 302) des cas, un inhibiteur non nucleosidique de la transcriptase inverse dans 34,1 % (n = 169) des prescriptions et un inhibiteur de protease chez 12,3 % (n = 61) des PVVIH. Le temps median du questionnaire etait de 7,4 minutes. Les PVVIH declaraient consommer dans 9,3 % (n = 46) des cas des corticoides, et dans 10,1 % (n = 50) des inhibiteurs de la pompe a protons. Dans 9,3 % (n = 46) des cas, les ordonnances n’etaient pas respectees, et 22,8 % (n = 113) pratiquaient l’automedication. Une consommation de drogues dans les trois derniers mois etait declaree par 10,9 % des patients (n = 54), ainsi qu’une prise d’autres substances actives (phytotherapie, homeopathie, complements alimentaires) pour 19,3 % (n = 96) des PVVIH. Une co-medication ou prise d’autres substances actives a ete revelee pendant la consultation dans 32,1 % (n = 159) des cas. Une potentielle interaction etait demasquee chez 10,7 % (n = 53) des PVVIH interroges conduisant a une modification du traitement pour 5,0 % (n = 25) des PVVIH. Conclusion Un temps dedie et un questionnaire standardise permettent de mettre en evidence des co-medications meconnues et de potentielles interactions. Ceci constitue desormais un enjeu majeur dans la prise en charge globale des PVVIH.

Annual incidence rates of varicella infection in the general population in France have been rather stable since 1991 when clinical surveillance started. Rates however show a statistically significant increase over time in children aged 0–3 years, and a decline in older individuals. A significant increase in day-care enrolment and structures’ capacity in France was also observed in the last decade. In this work we investigate the potential interplay between an increase of contacts of young children possibly caused by earlier socialization in the community and varicella transmission dynamics. To this aim, we develop an age-structured mathematical model, informed with historical demographic data and contact matrix estimates in the country, accounting for longitudinal linear increase of early childhood contacts. While the reported overall varicella incidence is well reproduced independently of mixing variations, age-specific empirical trends are better captured by accounting for an increase in contacts among pre-school children in the last decades. We found that the varicella data are consistent with a 30% increase in the number of contacts at day-care facilities, which would imply a 50% growth in the contribution of 0-3y old children to overall yearly infections in 1991–2015. Our findings suggest that an earlier exposure to pathogens due to changes in day-care contact patterns, represents a plausible explanation for the epidemiological patterns observed in France. Obtained results suggest that considering temporal changes in social factors in addition to demographic ones is critical to correctly interpret varicella transmission dynamics., Author summary During the last decades, an increasing circulation of varicella in the early childhood has been observed in France. A plausible explanation of this trend may rely on the progressive increase of day-care attendance in the past years, which could have anticipated the exposure of young children to the infection. We propose a retrospective modelling study to assess whether the varicella dynamics in France since 1991 can be explained in terms of increasing day-care contacts of children under 3 years of age. To this aim, we develop a model including demographic changes and variations in age-specific contact rates over time. Our findings suggest that a 30% increase of day-care contacts in early childhood can explain the observed epidemiological trends. Obtained results highlight that temporal changes in contact patterns can significantly affect the transmission of childhood infectious diseases and should therefore be considered when investigating medium and long-term epidemiological patterns. A better understanding of the interplay between changing social behavior and disease transmission can help the interpretation of surveillance data and the design of effective and targeted intervention strategies.

Background: Large measles and mumps outbreaks recently occurred throughout Europe and the United States. Aim: Our aim was to estimate and map the risk of resurgence for measles, mumps and rubella in France. Methods: We used a multi-cohort model combining seroprevalence information, vaccine coverage and social contact data. Results: The overall outbreak risk for France in 2018 was highest for mumps, remained significant for measles despite a recent measles outbreak and was low for rubella. Outbreak risks were heterogeneous between departments, as the effective reproduction numbers for 2018 ranged from 1.08 to 3.66. The seroprevalence, and therefore the risk of measles and rubella infection, differed significantly between mates and females. There was a lower seroprevalence, and therefore a higher risk, for males. Infants of less thane year would be seriously affected in a future outbreak of measles, mumps or rubella, but the highest overall caseload contribution would come from teenagers and young adults (10-25 years old). Conclusions: The high risk for teenagers and young adults is of concern in view of their vulnerability to more severe measles, mumps and rubella disease and complications. NH gratefully acknowledges the support from the University of Antwerp scientific chair in Evidence-Based Vaccinology, which was financed by a gift from Pfizer (2009-2017) and GlaxoSmithKline (2016). This project was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement 682540 - TransMID). GB gratefully acknowledges special research funding provided by Hasselt University (BOF14BL07). SA gratefully acknowledges support by the Research Fund of Hasselt University (Grant BOF11NI31). GB gratefully acknowledges special research funding provided by Hasselt University (BOF14BL07). SA gratefully acknowledges support by the Research Fund of Hasselt University (Grant BOF11NI31).

International audience; Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists.Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend.Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02).Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Bloodstream infections (BSIs) are common, however international guidelines are available only for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and candidaemia. This international ESCMID cross-sectional survey, open from December 2016 to February 2017, explored the management of BSIs by infection specialists. All infection specialists (senior or trainees) giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting uncomplicated BSI cases. A total of 616 professionals from 56 countries participated [333/616 (54%) infectious diseases specialists, 188/616 (31%) clinical microbiologists], of whom 76% (468/616) were members of an antimicrobial stewardship team. Large variations in practice were noted, in particular for the Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa vignettes. Echocardiography was considered standard of care by 81% (373/459) of participants for MRSA, 78% (400/510) for methicillin-susceptible S. aureus and 60% (236/395) for Candida albicans. Antimicrobial combination therapy was recommended by 2% (8/360) of respondents for C. albicans, 11% (43/378) for E. coli, 27% (114/420) for MRSA and 39% (155/393) for E. faecalis. Intravenous-to-oral switch was considered in 68% (285/418) for MRSA, 79% (306/388) for E. faecalis, 72% (264/366) for P. aeruginosa and 75% (270/362) for C. albicans. In multivariable analysis, IDSA guideline-compliant practice was more frequent among participants belonging to an antimicrobial stewardship team (aOR = 1.7, P = 0.018 for the MRSA vignette; and aOR = 2.0, P = 0.008 for the candidaemia vignette). This survey showed large variations in practice among infection specialists. International guidelines on management of BSI are urgently needed. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Introduction Les modalites de l’antibiotherapie, notamment la date optimale du relais oral, ne sont pas definies au cours du traitement des abces cerebraux. L’objectif de cette etude est d’evaluer le pronostic des patients selon la date d’un eventuel relais oral de l’antibiotherapie. Materiels et methodes Etude retrospective monocentrique incluant des adultes hospitalises pour abces ou empyeme cerebral documentes (01/2007–06/2018). Etaient exclus : contexte d’endocardite, abces a Nocardia, Aspergillus, Toxoplama, Ecchinococcus, Mycobacterium. Les donnees recueillies concernaient : le terrain, les symptomes et scores de gravite a l’admission, les microorganismes identifies et l’antibiotherapie recue. Le pronostic etait evalue ≥ 3 mois apres arret du traitement. Les patients ayant recu une antibiotherapie orale pendant au moins la moitie de la duree totale de traitement (PO) etaient compares a ceux ayant recu un traitement intraveineux prolonge (IV). Les variables continues sont presentees avec leur mediane et intervalles interquartiles. Les groupes ont ete compares en analyse univariee. Resultats Sur 82 patients ayant des abces/empyemes cerebraux, 47 ont ete inclus dont 33 hommes (70 %), âge median 55 ans [42–68]. Le groupe PO comportait 16 (34 %) patients. Les abces etaient dus a des streptocoques (n = 25), anaerobies (n = 24), staphylocoques (n = 8), bacilles Gram negatif (n = 7) et actinomyces (n = 6). Le qSOFA etait ≥ 2 seulement chez 1 patient PO contre aucun IV. Les patients IV etaient davantage hospitalises en reanimation (20 vs 4 ; p = 0,01). L’antibiotherapie probabiliste initiale comportait une cephalosporine de 3e generation (n = 39, 83 %) et un nitroimidazole (n = 38, 81 %) dans les deux groupes. La duree mediane de l’antibiotherapie etait de 42 jours [42–54]. Un relais oral a ete realise chez 23 patients (49 %) dans un delai median de 21j [11–28] mais seulement 16 patients correspondaient au groupe PO, avec un delai median de relais oral apres 15j de traitement IV [9–19]. Les antibiotiques PO etaient : clindamycine (n = 8), cotrimoxazole (n = 4), metronidazole (n = 1) et l’association rifampicine et fluoroquinolone (n = 2). Le pronostic a ete evalue avec un delai median de 202j [18-645] et n’etait pas different entre les groupes IV et PO : 10 deces (9 vs 1 ; p = 0,09) dans un delai median de 27j [19–55], 3 recidives (2 vs 1), 10 reprises chirurgicales (4 vs 6 ; p = 0,051) et 17 patients avec sequelles neurologiques (12 vs 5 ; p = 0,61). Conclusion Les abces cerebraux sont des infections severes. Neanmoins un relais oral de l’antibiotherapie pourrait etre envisage apres 15 jours de voie IV sans modifier le pronostic. L’extension de la cohorte en multicentrique pourrait permettre de renforcer les resultats.

Antimicrobial stewardship (AMS) is the cornerstone activity in the combat against antimicrobial resistance. In order to ensure sustainable deployment and development of AMS, a strategic and regulatory framework needs to be provided by national healthcare authorities. Experts from 32 European countries, Israel and Turkey were invited to participate in a cross-sectional internet-based survey from October 2016 to May 2017 on the legal framework and mandatory components (structures, activities) of AMS in hospitals, i.e. components required by legislation or regulations. We collected data from 25 countries and two regions (in countries with federal health administration). Laws regulating AMS existed in seven countries and one region. Other health ministry regulations were applicable in 13 countries and one region. National strategies and/or action plans approved by ministries of health were in place in 13 countries and one region. Conversely, five countries and one region had no regulation of AMS in hospitals. Funding for AMS in hospitals was provided in five countries and one region. Eight countries and one region reported mandatory AMS structures and activities complying with the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) structure, policy and practice indicators. In 10/27 cases, however, the mandatory AMS activities were not being fully carried out. The survey showed heterogeneous legal frameworks for AMS in hospitals, and in many countries it was even lacking. The situation may be critical in countries with poor control of antimicrobial use and resistance. Recent international initiatives calling on policy-makers to address the threat of antimicrobial resistance could yield improvement., peer-reviewed

Objectives To assess the perceptions, attitudes, and practices of French junior physicians regarding antibiotic use and resistance, and then to identify the characteristics of junior physicians associated with appropriate practices of antibiotic use. Method European junior physicians received an email invitation to complete a 49 item web questionnaire between September 2015 and January 2016. We present the French data. Multivariate regression models were used to identify the characteristics of junior physicians associated with appropriate prescription practices and with consideration of the antibiotic prescription consequences. Results The questionnaire was completed by 641 junior physicians: family medicine (37%), other medical specialties (e.g., pediatrics, internal medicine, neurology: 45%), surgical specialties (11%), and anesthesiology-intensive care specialty (7%). Most respondents (93%) declared being aware of the risk of bacterial resistance and 41% acknowledged prescribing antibiotics more often than necessary. Two factors were independently associated with appropriate prescription practices: a high perceived level of education on antibiotic use (OR = 1.51; 95% CI [1.01–2.30]) and a medical specialty (OR = 1.69; 95% CI [1.16–2.46]). Factors independently associated with taking into account adverse events of antibiotics were a good perceived knowledge of antibiotics (OR = 3.71; 95% CI [2.09–6.61]), and a high perceived education level on antibiotics (OR = 1.70; 95% CI [1.11–2.58]). Conclusion Our data can help better define interventions targeting junior physicians in antibiotic stewardship programs.

Tuberculous lesions of the oral cavity are rare and can be a diagnostic challenge, particularly in young immunocompetent patients. Most of the cases in the literature are secondary to pulmonary disease, whereas primary form is uncommon. This paper presents a case of gingival tuberculosis in a 26-year-old Indian female patient, manifesting as a rapidly extensive ulcer. The diagnosis was confirmed by histopathology and immunological investigations. Although oral manifestations of tuberculosis are rare, clinicians should include them in the differential diagnosis of various types of oral ulcers. An early diagnosis with a prompt treatment can prevent complications and potential contaminations.

Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables.Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated.Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen's κ, -0.13 to -0.24).Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome.

International audience; INTRODUCTION: We aimed to determine the limbal lighting illuminance thresholds (LLITs) required to trigger perception of sclerotic scatter at the opposite non-illuminated limbus (i.e. perception of a light limbal scleral arc) under different levels of ambient lighting illuminance (ALI). MATERIAL AND METHODS: Twenty healthy volunteers were enrolled. The iris shade (light or dark) was graded by retrieving the median value of the pixels of a pre-determined zone of a gray-level iris photograph. Mean keratometry and central corneal pachymetry were recorded. Each subject was asked to lie down, and the ALI at eye level was set to mesopic values (10, 20, 40 lux), then photopic values (60, 80, 100, 150, 200 lux). For each ALI level, a light beam of gradually increasing illuminance was applied to the right temporal limbus until the LLIT was reached, i.e. the level required to produce the faint light arc that is characteristic of sclerotic scatter at the nasal limbus. RESULTS: After log-log transformation, a linear relationship between the logarithm of ALI and the logarithm of the LLIT was found (p\textless0.001), a 10% increase in ALI being associated with an average increase in the LLIT of 28.9%. Higher keratometry values were associated with higher LLIT values (p = 0.008) under low ALI levels, but the coefficient of the interaction was very small, representing a very limited effect. Iris shade and central corneal thickness values were not significantly associated with the LLIT. We also developed a censored linear model for ALI values ≤ 40 lux, showing a linear relationship between ALI and the LLIT, in which the LLIT value was 34.4 times greater than the ALI value. CONCLUSION: Sclerotic scatter is more easily elicited under mesopic conditions than under photopic conditions and requires the LLIT value to be much higher than the ALI value, i.e. it requires extreme contrast

International guidelines are available to help physicians prescribe appropriate antibiotic regimens to patients with infective endocarditis (IE). However some topics of these guidelines are controversial. We conducted an international survey to assess physicians' adherence to these guidelines, focusing on these controversial items. An invitation to participate to a 15-question online survey was sent in 2012-2013 to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members, scientific societies and corresponding authors of publications on IE mentioned in PubMed from 1990 to 2012, inclusive. Eight hundred thirty-seven physicians participated in the survey, and 625 (74.7%) completed it over the first question. The results showed great heterogeneity of practices. Claiming to follow guidelines was marginally associated with more guideline -based strategies. Gentamicin use depended on causative pathogens (p

WOS: 000379252100027, PubMed ID: 27085724, There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Introduction Ceftolozane tazobactam (CT) est l’association antibiotique d’une nouvelle cephalosporine et d’un inhibiteur de beta lactamase qui a une activite sur Pseudomonas aeruginosa (PSA) y compris les souches presentant des resistances microbiologiques. Nous nous sommes interesses a son efficacite sur les cas d’infections a PSA extremement resistants. Materiels et methodes Etude retrospective nationale des infections a PSA XDR traitees par CT identifiees avant commercialisation. Donnes anamnestiques, cliniques, microbiologiques, et evolution recueillies par le clinicien en charge du patient a l’aide d’un questionnaire standardise. Le caractere XDR etait classiquement defini par la resistance a au moins un des agents dans toutes les classes d’antibiotiques anti-PSA sauf 2 ou moins. L’evolution etait evaluee en in de traitement et a J28 ou a la sortie de l’hopital. Resultats Au total 15 patients ont ete traites par CT (14 adultes et 1 enfant de 3 ans) dans 7 hopitaux du 3 mars au 11 novembre 2016 ; 10 d’entre eux etaient immunodeprimes. Le CT a ete prescrit en reanimation pour 8 patients, en service de medecine pour 6 et en chirurgie pour 1. Concernant les patients de reanimation le score SOFA moyen etait de 7,6 ± 4,0. Au total, 6 patients etaient sous ventilation mecanique et 5 recevaient des amines vasopressives Le point de depart de l’infection etait une pneumonie ( n = 7) dont 6 acquises sous ventilation mecanique, une infection urinaire ( n = 3), une infection digestives ( n = 2), 1 meningite, 1 infection de prothese vasculaire et 1 infection osteo articulaire. L’infection etait polymicrobienne dans 8 cas associant : une enterobacteries ( n = 3), Stenotrophomonas maltophilia ( n = 1), enterococcus faecalis ( n = 1), citrobacter koseri ( n = 1), une autre souche de PSA ( n = 1), et staphylococcus epidermidis ( n = 1). Le CT etait prescrit en moyenne apres 2,5 lignes d’antibiotherpie prealables (0–6) et la duree moyenne de traitement etait de 19,3 jours avec une posologie moyenne de 5,0 g/j. Le C/T etait prescrit en monotherapie chez 5 patients et 10 recevaient une autre antibiotherapie (colistine : 6, aminoglycosides : 2, fluoroquinolones : 1). A la fin du traitement par CT une guerison etait observee chez 10/15 patients (66 %), la mortalite tout cause confondue etait de 4/15 patients dont un en echec clinique. La guerison microbiologique etait obtenue chez 6/8 patients ; 7 patients n’ont pas eu de nouveaux prelevements microbiologiques et 2 ont ete classes en echec microbiologique. A J28 et/ou a la sortie de l’hopital, 8/9 patients etaient consideres comme gueris et 1 avait presente une recidive septique. Conclusion Le CT semble une option efficace et peu toxique lors des infections severes a PSA XDR.

US and European guidelines recommend a daily divided gentamicin dose (3 mg/kg in two or three equally divided doses) for the treatment of infective endocarditis caused by staphylococci or enterococci, but once-daily dosing (3 mg/kg/day) is recommended for streptococcal endocarditis. However, studies have recommended the use of higher doses of gentamicin (4 or ≥5 mg/kg/day) administered once-daily. A survey was conducted in France by mailing a questionnaire to the 595 members of the French Infectious Disease Society regarding their gentamicin prescription patterns in infective endocarditis, focusing on the dosing regimen. The survey was answered by 137 physicians (23%). The proportions of physicians following guideline-based regimens were similar for each organism (30.9%, 38.8%, and 39.4% for staphylococci, enterococci, and streptococci, respectively [p=0.26]). In contrast, the proportions of physicians following literature-based regimens were significantly different for each organism (59.6%, 42.5%, and 27.7% for staphylococci, enterococci, and streptococci, respectively [p