Laurence Watier

Background: Older adults in nursing homes face high influenza-related morbidity and mortality due to immunosenescence and comorbidities, which may reduce vaccine effectiveness. High-dose (HD) influenza vaccine, containing four times more antigen than standard-dose (SD) formulations, aim to compensate for this impaired immune response. Objectives: To compare the Relative Vaccine Effectiveness (rVE) of HD versus SD influenza vaccines against influenza-related hospitalisations (primary), and hospitalisations due to pneumonia or combined influenza/pneumonia (secondary) in nursing home residents aged ≥65 years. Study Design: Nationwide retrospective cohort (French SNDS). Residents vaccinated between 1 September 2022, and 31 March 2023, were followed until 30 June 2023, discharge or death. Facilities with in-house pharmacies were excluded. Exposures/Outcomes: HD vs. SD influenza vaccine (pharmacy dispensing codes). Hospitalisations identified by ICD-10 discharge codes. Methods: HD and SD recipients were matched 1:1 using propensity scores with exact matching on sex, age group, region and vaccination week. Incidence rate ratios (IRR) were estimated using Poisson/negative binomial models. rVE = (1–IRR) × 100. Results: Among 315 239 residents (123 720 HD; 191 519 SD), 76 858 pairs were matched (mean age 88 years; 75% women). Influenza hospitalisation rates were 302 vs. 438 per 100 000 person-years, corresponding to an rVE of 30.8% (95% CI: 11.8–45.7; P = .0029). No significant rVE was observed for pneumonia or combined outcomes. Conclusions and Relevance: HD vaccine was associated with a significant reduction in influenza-related hospitalisations in French nursing home residents, supporting preferential HD use in this high-risk population. Residual confounding cannot be excluded, and vaccine safety was not assessed in the present analysis.

Background: Respiratory syncytial virus (RSV) and influenza virus are leading causes of respiratory infections, causing substantial numbers of hospitalizations and deaths, particularly among vulnerable groups such as infants and older adults. While the burden of influenza virus infection is well-documented, the burden of RSV infection in the adult population is often underestimated due to diagnostic challenges and infrequent standard-of-care testing. This study aimed to estimate the incidence of general practitioner (GP) visits, hospitalizations, and deaths attributable to RSV and influenza virus infections in French adults aged ≥50 years, with a focus on ≥65 years, using a time-series model-based approach. In addition, costs associated with hospitalizations were calculated. Methods: Cyclic Poisson regression models and weekly data from French medical administrative databases and electronic medical records over ten epidemic seasons (2010–2020) were used to estimate incidences for RSV and influenza. The results were stratified by age group, diagnosis causes (respiratory and cardiorespiratory) and diagnosis type (primary and secondary). Average costs per hospitalization were calculated and multiplied by the number of hospitalizations estimated. Results: Among adults aged ≥65 years, we estimated RSV infection was responsible for 647 619 GP visits 24 319 hospitalizations, and 878 deaths per year. Incidence rates for GP visits for RSV were twice as large as for influenza; hospitalization rates were similar and mortality was lower. The mean annual cost of RSV-attributable hospitalizations was 105 million €, similar to influenza. Conclusions: This study highlighted the burden of RSV disease in the adult population in France is higher than previous reported. We envisage that this model-based approach will be instrumental in evaluating the impact of RSV vaccination campaigns.

Background: A French cohort study (2021/2022 influenza season) found the high‐dose influenza vaccine (HD) more effective than standard‐dose vaccines (SDs) in preventing influenza‐related hospitalizations in the elderly. The study continued to refine results and validate these findings. Methods: Data from community‐dwelling 65+ adults who received HD or SD during the 2022/2023 vaccination campaign were extracted from the National Health database. Hospitalizations were recorded from 14 days postvaccination until June 30, 2023. HD and SD recipients were matched using a propensity score. Associations between vaccines and hospitalizations were assessed by estimating incidence rate ratios and converting them to HD vs. SD vaccine relative effectiveness (rVE). Results: A total of 675,412 HD recipients were matched to 2,701,648 SD recipients. The rVE for influenza‐related hospitalizations was 27.4% [95% CI: 19.8; 34.3]. It ranged from 22.7% [9.8; 33.6] to 33.6% [21.2; 44.0] across age groups, indicating that HD consistently outperformed SDs in preventing influenza‐related hospitalizations, with the highest effect observed in 85+. Conclusions: Our study is the first to publish rVE data comparing HD and SDs in a real‐world setting in France for the 2022/2023 influenza season. Its findings reaffirm the benefit of HD vs. SDs. HD could help reduce the burden of severe respiratory infections in the elderly.

Objective: This study aimed to provide real-life data on COPD healthcare resource utilization (HCRU)-related costs in patients receiving triple therapy and to quantify the economic burden of uncontrolled COPD patients (ie, ≥ 1 severe or 2 moderate exacerbations within 12 months before inclusion and at least one exacerbation under treatment) versus controlled COPD patients and the general population. Methods: Patients aged over 40 years receiving triple therapy in 2015 (ie, long-acting ß 2-agonist, long-acting anticholinergic and inhaled corticosteroids) for at least 90 continuous days were included. The index date was defined as the 91st day of triple therapy exposure. Patients were followed for up to 5 years. HCRU-costs were computed by calendar year in controlled and uncontrolled COPD patients and in the general population. The association between costs and COPD has been estimated, for each calendar year, using GEE with a negative binomial distribution. Results: Among the 186,963 patients included, 21.2% (N= 39,647) of patients were identified as uncontrolled. Among these, the average cost related to HCRU per patient was around 12,000€ by year. Hospitalizations, drugs and medical devices represented approximately 2/3 of expenses. Costs were in average 1.25 higher than in controlled COPD treated patients and 2.7 higher than the general population. Attributable costs to COPD in uncontrolled patients were estimated at approximately € 7,600 per patient each year. Conclusion: This study offers a robust representation of health care resource consumption and related costs of COPD patients receiving triple therapy in France over several years with a focus on uncontrolled patients.

Summary: Background: The COVID-19 pandemic led to major disruptions in healthcare services at the hospital and community levels. The resulting impact on antibiotic resistance (ABR) in hospitals is difficult to predict. Methods: We exploited data from the French national surveillance system over four years (2019-2022) including 414 hospitals across 12 French regions. We evaluated changes in annual antibiotic use compared to 2019 using multiple comparison tests. We also compiled a large dataset of 692,551 incident isolates for five antibiotic-bacterium pairs. Using negative binomial regression models accounting for autocorrelation and antibiotic use, we evaluated associations between resistant isolates incidence and COVID-19 indicators (pandemic periods or intubated COVID-19 patient prevalence). We investigated how these associations varied specifically in ICUs ( n =85) and across geographical regions. Findings: The use of some antibiotics, including azithromycin, imipenem and meropenem, significantly increased between 2020 and 2022. Concomitantly, the incidence of methicillin-resistant Staphylococcus aureus (up to 37%, 95% CI: 18-53%) and ESBL-producing Escherichia coli (up to 33%, 95% CI: 16-46%) isolates significantly decreased in hospitals and ICUs during the pandemic. A transient decrease in ICUs was also observed for ESBL-producing Klebsiella pneumoniae during periods of strong anti-COVID-19 interventions in the community (24%, 95% CI: 6-38%). No significant changes for ESBL-producing Enterobacter cloacae complex were observed. Very interestingly, the incidence of carbapenem-resistant Pseudomonas aeruginosa isolates was associated with COVID-19 intubation prevalence in hospitals (pP. aeruginosa to all tested antibiotics in 2022 compared to 2017, using point prevalence survey results. Conversely, one study focusing on US Veterans Affairs hospitals showed increased incidence and resistance of healthcare-associated carbapenem-resistant P. aeruginosa (CR-PA) infections during the pandemic. Most studies used univariate statistical approaches. Only two studies included COVID-19-related variables in their models; they found no association with MRSA or extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae . Added value of this study: Here, we provide the first evaluation of the impact of the pandemic on antibiotic consumption and resistance for five antibiotic-bacterium pairs (MRSA, CR-PA, ESBL-producing E. coli , ESBL-producing K. pneumoniae , and ESBL-producing E. cloacae complex) in hospitals, at the national and regional scales. By analyzing French surveillance data from the SPARES database including 414 hospitals that represent up to 14% of French hospitals, we evaluated annual changes in antibiotic use and quantified the impacts at the weekly level of the COVID-19 pandemic on the incidence of five of the most prevalent resistant bacteria in France. Accounting for autocorrelation and antibiotic use, factors that were not considered in previous studies, we report a significant positive association between the weekly incidence of CR-PA isolates and the prevalence of intubated COVID-19 patients in the preceding weeks. Carbapenem use and intubation being risk factors of CR-PA infections, our results suggest a direct impact of the pandemic on CR-PA epidemiology. Inversely, we show that the incidence of ESBL-producing E. coli and MRSA isolates decreased after the start of the first pandemic wave at the hospital level but also in ICUs. The fine grain analysis across 12 French administrative regions revealed regional heterogeneities, but highlighted consistent associations in the regions most affected by the COVID-19 pandemic. Implications of all the available evidence: Pandemics not only destabilize healthcare systems by adding pressure and changing healthcare worker behaviors, but also influence the epidemiology of other infectious diseases as shown in our study. We specifically highlight the contrasting effects of the COVID-19 pandemic on ABR in French hospitals, associated with an increase in CR-PA isolate incidence but a general decrease in ESBL-producing E. coli and MRSA. This work highlights how national-scale hospital surveillance systems such as SPARES that collect data at the weekly level are key to capture the evolving impacts of pandemics. They also allow to generate hypotheses on the potential mechanisms of action of the pandemic on ABR epidemiology, as showcased by the analysis of CR-PA isolates incidence, and thereby participate in the improvement of healthcare systems in pandemic context.

Background A French retrospective observational cohort study conducted during the 2021/22 influenza season found that the high-dose influenza vaccine (HD) was more effective than standard-dose vaccines (SDs) in preventing influenza-related hospitalizations in the elderly. The study continued during the 2022/23 season to obtain more accurate results and validate the findings during a different influenza season. Material and methods Data from community-dwelling 65+ adults vaccinated with HD or SD during the 2022/23 vaccination campaign were extracted from the National Health database. Hospitalizations were recorded from 14 days after vaccination until 30 June 2023. HD and SD recipients were matched using a propensity score with an exact constraint on age, sex, vaccination week, and geographical region. Associations between vaccines and hospitalizations (influenza or non-influenza related) were assessed by estimating incidence rate ratios and converting them to HD vs SD vaccine relative effectiveness (rVE). Results 675,412 HD recipients were matched to 2,701,648 SD recipients. The HD vs SD rVE for influenza-related hospitalizations was 27.39% [95%CI: 19.79;34.27]. It ranged from 22.65% [9.84;33.64] to 33.55% [21.19;43.98] across age groups, indicating that HD resulted in consistently better protection than SDs against influenza-related hospitalizations in all age groups, with the highest effect observed in 85+. Conclusion Our study is the first to publish rVE data comparing HD and SD in France, for the 2022/23 influenza season. Its findings reaffirm the benefit of HD vs SD in reducing influenza-related hospitalizations in a real-world setting. HD could help reduce the burden of severe respiratory infections in the elderly. Registration number: Not applicable. Take-home message In France, during the 2022/23 influenza season, the high-dose vaccine has reduced influenza-related hospitalizations by 27.4% compared to standard-dose vaccines among community-dwelling 65+ adults, with a clinical benefit observed across all age groups.

Purpose: Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes. Patients and Methods: Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured. Results: Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001). Conclusion: The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France’s largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.

In France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets for future public health actions. Using data from the French National Health Data System, we described and compared the individual characteristics of patients with and without an antibiotic prescription. The prescribed antibiotics (ATC-J01) were detailed and compared between 2019 and 2020. Antibiotic prescribing indicators that take prescriber activity into account were estimated and compared. Patients who were female, advanced age, and the presence of comorbidities were associated with antibiotic prescriptions. The overall prescription rate was estimated at 134 per 1000 consultations and 326 per 1000 patients seen in 2019. General practitioners (GPs), dentists and paediatricians were associated with 78.0%, 12.2% and 2.2% of antibiotic prescriptions, respectively, with high prescription rates (391, 447, and 313 p. 1000 patients seen, respectively). In comparison with 2019, this rate decreased in 2020 for paediatricians (−30.4%) and GPs (−17.9%) whereas it increased among dentists (+17.9%). The reduction was twice as high among the male prescribers than among their female counterparts (−26.6 and −12.0, respectively). The reduction in prescriptions observed in 2020 (−18.2%) was more marked in children (−35.8%) but less so among individuals ≥65 years (−13.1%) and those with comorbidities (−12.5%). The decrease in penicillin prescriptions represents 67.3% of the overall reduction observed in 2020. The heterogeneous decrease in prescriptions by age and antibiotic class could be explained by the impact of COVID-19 control measures on the spread of respiratory viruses; thus, a substantial proportion of the prescriptions avoided in 2020 is likely inappropriate, particularly among children. In order to keep the rate of prescriptions comparable to that observed in 2020, male prescribers, paediatricians and GPs should be encouraged to maintain that level, while a campaign to raise awareness of the appropriate use of antibiotics should be aimed at dentists in particular.