Enterococcal endocarditis management and relapses.

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.

Multivariate joint model under competing risks to predict death of hospitalized patients for SARS-CoV-2 infection.

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.

Evaluation of iron metabolism in hospitalized COVID-19 patients.

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.

Pregnant women with mild COVID-19 followed in community setting by telemedicine, and factors associated with unfavorable outcome.

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.

Determinants of adherence to oral hygiene prophylaxis guidelines in patients with previous infective endocarditis.

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.

Adaptation and Response of a Major Parisian Referral Hospital to the COVID-19 Surge: A Qualitative Study.

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.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study.

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.

A Healthcare-Associated Infection With Monkeypox Virus of a Healthcare Worker During the 2022 Outbreak.

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.

Characteristics and outcomes of asthmatic outpatients with COVID-19 who receive home telesurveillance.

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.

Cost-effectiveness of strategies to control the spread of carbapenemase-producing Enterobacterales in hospitals: a modelling study.

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.

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

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.

Contributions and challenges of community pharmacists during the COVID-19 pandemic: a qualitative study.

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.

Contribution of Clinical Metagenomics to the Diagnosis of Bone and Joint Infections.

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.

Perceptions, current practices, and interventions of community pharmacists regarding antimicrobial stewardship: A qualitative study.

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.