Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

SARS-CoV-2 nosocomial infection acquired in a French university hospital during the 1st wave of the Covid-19 pandemic, a prospective study.

BACKGROUND: In healthcare facilities, nosocomial transmissions of respiratory viruses are a major issue. SARS-CoV-2 is not exempt from nosocomial transmission. Our goals were to describe COVID-19 nosocomial cases during the first pandemic wave among patients in a French university hospital and compliance with hygiene measures. METHODS: We conducted a prospective observational study in Grenoble Alpes University Hospital from 01/03/2020 to 11/05/2020. We included all hospitalised patients with a documented SARS-CoV-2 diagnosis. Nosocomial case was defined by a delay of 5 days between hospitalisation and first symptoms. Hygiene measures were evaluated between 11/05/2020 and 22/05/2020. Lockdown measures were effective in France on 17/03/2020 and ended on 11/05/2020. Systematic wearing of mask was mandatory for all healthcare workers (HCW) and visits were prohibited in our institution from 13/03/2021 and for the duration of the lockdown period. RESULTS: Among 259 patients included, 14 (5.4%) were considered as nosocomial COVID-19. Median time before symptom onset was 25 days (interquartile range: 12-42). Eleven patients (79%) had risk factors for severe COVID-19. Five died (36%) including 4 deaths attributable to COVID-19. Two clusters were identified. The first cluster had 5 cases including 3 nosocomial acquisitions and no tested HCWs were positive. The second cluster had 3 cases including 2 nosocomial cases and 4 HCWs were positive. Surgical mask wearing and hand hygiene compliance were adequate for 95% and 61% of HCWs, respectively. CONCLUSIONS: The number of nosocomial COVID-19 cases in our hospital was low. Compliance regarding mask wearing, hand hygiene and lockdown measures drastically reduced transmission of the virus. Monitoring of nosocomial COVID-19 cases during the first wave enabled us to determine to what extent the hygiene measures taken were effective and patients protected. Trial registration Study ethics approval was obtained retrospectively on 30 September 2020 (CECIC Rhône-Alpes-Auvergne, Clermont-Ferrand, IRB 5891).

COVID-19 in clinical practice: A narrative synthesis.

The coronavirus disease 2019 (COVID-19) was first reported in the city of Wuhan, China. The disease rapidly spread to the rest of China, to Southern-East Asia, then to Europe, America, and on to the rest of the world. COVID-19 is associated with a betacoronavirus named SARS-CoV-2. The virus penetrates the organism through the respiratory tract, conveyed by contaminated droplets. The main cell receptor targeted is the surface-bound ACE-2. As of the 26th July 2020, 15,200,000 COVID-19 cases and 650,000 deaths were reported worldwide. The mortality rate is estimated between 1.3 and 18.3%. The reproductive rate without any public health intervention is estimated around 4-5.1 in France. Most hospitalized patients for COVID-19 present respiratory symptoms, which in some cases is associated with fever. Up to 86% of admissions to ICU are related to acute respiratory failure. To date, no anti-viral therapy has proven its efficacy considering randomized trials. Only immunomodulatory treatments such as corticosteroids have shown to cause significant improvement in patient outcome.

Chronic disseminated candidiasis and acute leukemia: Impact on survival and hematopoietic stem cell transplantation agenda.

OBJECTIVES: To study the management of chronic disseminated candidiasis (CDC) in patients presenting with acute leukemia. PATIENTS AND METHODS: Single-center retrospective study of acute leukemia patients (2006-2015) to investigate three aspects of CDC: its impact on the time interval between diagnosis and hematopoietic stem cell transplantation, when required (non-parametric Wilcoxon-Mann-Whitney test); its impact on overall survival (Cox proportional hazard regression model); antifungal therapeutic strategies implemented. RESULTS: A total of 639 patients presenting with acute leukemia were included; 144 were transplanted and 29 developed CDC. CDC did not significantly increase the time interval between diagnosis and transplantation, nor did it impact the overall survival of recipients. An improved overall survival was observed in non-transplanted acute leukemia patients presenting with CDC. CONCLUSION: CDC should not postpone transplantation if antifungal treatment is optimized.

General practitioners' perceptions of vaccination controversies: a French nationwide cross-sectional study.

OBJECTIVES: We aimed to study general practitioners' (GPs') perceptions of vaccines that have been a subject of controversy in France. METHODS: A cross-sectional survey in 2014 asked a representative national sample of GPs, randomly selected from the exhaustive database of health professionals in France, about their perceptions of the likelihood of serious adverse events potentially associated with six different vaccines: for two of them the association was based on some scientific evidence, whereas for the other four this is not the case. We performed a cluster analysis to construct a typology of GPs' perceptions about the likelihood of these potential six associations. Factors associated with certain clusters of interest were identified using logistic regression models. RESULTS: Overall, 1582 GPs participated in the questionnaire survey (1582/1712 GPs who agreed to participate, 92%). Cluster analysis identified four groups of GPs according to their susceptibility to vaccine controversies: 1) limited susceptibility to controversies (52%); 2) overall unsure, but rejected the association between hepatitis B vaccine and multiple sclerosis (32%); 3) highly susceptible to controversies (11%); and 4) unsure (5%). We found that GPs who occasionally practised alternative medicine (OR 2.71, 95% CI 1.65-4.45), and those who considered information provided by mass media as reliable (OR 2.04, 95% CI 1.65-3.99) were more susceptible to controversies. CONCLUSIONS: GPs had different profiles of susceptibility to vaccination controversies, and most of their perceptions of these controversies were not based on scientific evidence.

General practitioners and vaccination of children presenting with a benign infection.

PURPOSE: To assess the self-reported vaccination behavior of general practitioners (GPs) when asked whether they would recommend the vaccination of a child presenting with a febrile uncomplicated common cold. METHODS: We performed a cross-sectional survey in 2014 on a national sample of GPs. GPs were randomly assigned to one of eight clinical vignettes, all describing a child presenting with an uncomplicated febrile common cold, but differing by age (4 or 11 months), temperature (38°C or 39°C), and the mother's emotional state (calm or worried). GPs were asked whether they would recommend immediate vaccination of the child with a hexavalent vaccine (diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, and hepatitis B), or postpone it. We investigated the relation between the GPs' recommendation to vaccinate, the clinical vignette's variables, and the GPs' perceptions, attitudes, and practices toward vaccination in a multivariate model. RESULTS: Among the 1582 participating GPs, 6% recommended immediate vaccination. This behavior was more frequent with a temperature of 38°C rather than 39°C (10% vs. 3%, P<0.001). GPs who felt comfortable giving explanations about vaccine safety were more likely to recommend immediate vaccination of the febrile child (P=0.045), but none of the other GPs' characteristics were associated with their vaccination behavior. CONCLUSIONS: Almost all GPs postponed the hexavalent vaccination of the febrile child presenting with an uncomplicated viral disease; fever being the major factor affecting their decision. More research is needed on vaccination responses in sick children, as well as clearer guidelines.

Discrepancies between general practitioners' vaccination recommendations for their patients and practices for their children.

OBJECTIVES: The objectives of our study were to describe the vaccination recommendations by general practitioners (GPs) for their patients and practices for their children, and to identify any discrepancies between them. METHODS: Applying multiple correspondence analysis and agglomerative hierarchical cluster analysis to data from a 2014 cross-sectional survey of a national sample of GPs, we constructed a typology based on the patterns of associations between GPs' vaccine recommendations to their patients and practices to their own children's vaccinations. RESULTS: This study includes the 1038 GPs who reported that they had at least one child aged 2-25 years. Nearly half (47%, 482/1021) reported that all of their children were vaccinated against hepatitis B but that they did not always recommend that vaccine to patients; the same discordance was observed among 36% (369/1027) for the measles-mumps-rubella vaccine, 19% (194/1013) to 28% (290/1019) for routine and catch-up meningococcal C vaccination, and 27% (136/496) for the human papillomavirus vaccine. Cluster analysis showed that 37% (95% CI 33%-39%) of GPs reported an above-average rate of systematic vaccine recommendations for their patients, and most reported that all their children were vaccinated (low level of discordance), whereas 60% (95% CI 58%-64%) had a high level of discordance, that is, most reported that their children were vaccinated, but did not always recommend the same vaccines to their patients. CONCLUSIONS: Many GPs do not report the same attitude concerning the vaccination of their children and their patients. The reasons underlying these discrepancies, possibly including vaccine hesitancy, should be investigated.

A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.

Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

Design of a national and regional survey among French general practitioners and method of the first wave of survey dedicated to vaccination.

OBJECTIVES: France is currently facing a vaccine-hesitancy crisis. We conducted a questionnaire-based telephone interview with a large sample of general practitioners (GPs) as they play a crucial role in the vaccination process. Our main objectives were to study the GPs' vaccination behaviors when it comes to their own vaccination and that of their relatives, and the vaccine recommendations made to their patients. We also aimed to understand their opinion related to the severity of vaccine-preventable diseases and to assess their trust in various sources of information. Finally, we enquired about their opinion in terms of vaccination-related tools that could help them in their daily practice. The article aimed to present the design of this panel and survey. PATIENTS AND METHODS: Four samples of GPs (one national and three regional) were selected among all the French GPs (metropolitan France) using random sampling. Five cross-sectional surveys should be conducted with that panel. The mean targeted sample size is 2350 GPs for each survey. The survey dedicated to vaccination was conducted by telephone or on the Internet. RESULTS: GPs were included in the survey between December 2013 and February 2014. The national sample included 1582 GPs (response rate: 46%) and the three regional samples included 1297 GPs (response rate: 44%). The survey dedicated to vaccination was conducted between April and July 2014; the national sample response rate was 92% (1582/1712). CONCLUSION: The results of the first wave of surveys, conducted on a large sample of French GPs, provide important information to guide the French vaccination policy.