BACKGROUND:Clinical decision support systems (CDSS), computerized tools that assist clinicians in making guideline-based decisions, may support antimicrobial prescribing in primary care. METHODS:Studies on CDSS implementation, use and outcomes in primary care on PubMed/MEDLINE and Embase were included up to June 2025. RESULTS:Of the 64 full-text articles assessed, 40 were included. Most were multicentric (n = 33, 82.5%) and conducted in high-income countries (n = 33, 82.5%), and 19 were randomized controlled trials (47.5%). CDSS mainly targeted respiratory infections (n = 24, 60%) and were integrated into electronic health records in 24 studies (60%). Implementation strategies were assessed in 19 studies with almost all using a multimodal approach, most commonly involving modification of health record systems (n = 18, 45%) and audit and feedback (n = 17, 42.5%). Adoption was highly variable: among the 11 studies reporting use, CDSS were used in more than half of consultations in only five studies. Among the 32 studies assessing clinical outcomes, 17 reported reduced overall antibiotic prescribing. Barriers to CDSS use included perceptions of redundancy, time consumption, language limitations, alert fatigue, technical issues and concerns about negative impacts on patient-doctors trust. CONCLUSION:CDSS may improve guideline-concordant antibiotic prescribing in primary care, but wide variability in implementation and real-world adoption limits generalizability and scalability.

Avian influenza continues to evolve as a zoonotic threat with important implications for clinical practice and global health preparedness. Sustained circulation in wild birds, repeated spillover into poultry, and an increasing number of infections across diverse mammalian hosts have reshaped exposure pathways and broadened the risk landscape for human infection. For clinicians, this evolving ecology translates into atypical presentations and increased diagnostic uncertainty. Recent global activity has been characterised by widespread animal outbreaks and the emergence of new transmission interfaces, including occupational exposures and livestock-associated events. Human infections remain largely zoonotic and geographically heterogeneous, with patterns influenced by surveillance intensity, exposure context, and healthcare access. We synthesise current evidence on the virology, transmission, global epidemiology, clinical manifestations, diagnosis, treatment, and prevention of avian influenza in humans. We highlight evolving mammalian adaptation and changing risk interfaces that complicate risk assessment. Improved clinician awareness, early diagnosis, and integrated One Health surveillance remain central to strengthening preparedness for future influenza threats.

Current guidelines for the management of meticillin-susceptible Staphyloccocus aureus bloodstream infection/bacteraemia (SAB) recommend intravenous (flu)cloxacillin as the first-line treatment. This is based on decades of clinical practice. The high acute kidney injury rates seen with (flu)cloxacillin in the recently published SNAP trial, which is the largest randomized clinical trial ever in S. aureus bacteraemia (SAB), shows us the need to regularly test and question our usual clinical practice. Acute kidney injury is common in SAB when high doses of (flu)cloxacillin are used. The contribution of (flu)cloxacillin to developing or exacerbating acute kidney injury is likely to have been under recognized until now. Caution needs to be taken with (flu)cloxacillin. Cefazolin provides a safer and equally efficacious treatment for SAB. We discuss how this new evidence might be combined with our existing knowledge and the results of the CloCeBa trial to guide us how to appropriately manage our patients.

Optimal implementation strategies and clinical outcomes of Clinical Decision Support Systems (CDSS) for antimicrobial prescribing in hospital settings have not been systemically evaluated. This review explores how CDSS for antimicrobial stewardship (AMS) have been implemented in secondary and tertiary care, focusing on strategies used, clinical and implementation outcomes. A systematic search was conducted including studies published up to December 2022. Primary studies describing CDSS implementation strategies in secondary and tertiary care were included. Strategies were analysed using the Expert Recommendations for Implementing Change (ERIC) framework. Implementation outcomes reported in the studies were extracted and categorized according to Proctor’s framework. Quality assessment was performed using the Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS). Screening of 2,189 papers identified 12 studies meeting inclusion criteria, all focusing on antimicrobial prescribing in high-income countries. Most CDSS were expert systems (n = 11), primarily designed for infectious disease physicians (n = 7). Pre-implementation assessments, such as workflow analysis, user surveys and multidisciplinary meetings, were conducted in only five of the 12 studies. Studies used a median of 11 out of 73 ERIC implementation strategies. The most frequently reported strategies belonged to the following ERIC categories: developing stakeholder interrelationships (n = 11), training and educating users (n = 11), evaluative strategies (n = 10), provision of interactive assistance (n = 5), adaptation and tailoring to context (n = 5). In contrast, strategies aimed at supporting clinicians (n = 3) and changing infrastructure (n = 2) were less commonly used. No study reported strategies related to patient and service user engagement or financial strategies. Clinical outcomes were considered effective in two studies and partially effective in four, while the remaining studies did not evaluate them. A median of three implementation outcomes was reported per study, with appropriateness (n = 10), adoption (n = 9) and acceptability (n = 9) being the most examined. Overall, initial adoption was slow but improved over time, enhancing compliance with policy indicators. The implementation strategies of CDSS for AMS in hospital settings are variably reported, with many studies providing limited detail on strategy selection, application, or outcomes, highlighting the need for more systematic and comprehensive evaluation in future research.

BACKGROUND:Although widely used, cefazolin efficacy for the treatment of meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia has not thus far been investigated in a clinical trial. In this study, we aimed to compare the efficacy and safety of cefazolin with that of cloxacillin in patients with MSSA bacteraemia. METHODS:We conducted an open-label, non-inferiority, randomised clinical trial in 21 university and non-university hospitals in France in adults (aged ≥18 years) with MSSA bacteraemia, without intravascular implant or suspicion of CNS infection. Participants were randomly assigned (1:1) to receive intravenously cefazolin (25-50 mg/kg every 8 h) or cloxacillin (25-50 mg/kg every 4-6 h) for the first 7 days of therapy using computer-generated blocks of various sizes and stratification on vascular-access associated bacteraemia and centre. Subsequent treatment was left to the choice of the investigator (total duration ≥14 days). The primary endpoint was a composite of sterile blood cultures at day 3 (day 5 for endocarditis) without relapse of bacteraemia, survival, and clinical success at day 90, and was assessed in the intention-to-treat population. A non-inferiority margin of 12% was chosen. This trial is registered on ClinicalTrials.gov (NCT03248063) and is complete. FINDINGS:Between Sept 5, 2018, and Nov 16, 2023, 315 participants were enrolled and assigned to cefazolin (n=158) or cloxacillin (n=157); 12 participants were excluded from analysis in the cefazolin group, and 11 in the cloxacillin group (final population of 146 in each group). Mean age was 62·7 years (SD 16·4), 215 (74%) participants were male, and race or ethnicity data were not collected. Median Pitt score was 0 (IQR 0-0). The primary endpoint was met in 109 (75%) of 146 participants in the cefazolin group versus 108 (74%) of 146 participants in the cloxacillin group (treatment difference -1%; 95% CI -11 to 9; p=0·012). At the end of study treatment, 22 (15%) of 146 participants assigned to cefazolin and 40 (27%) of 146 participants assigned to cloxacillin had had a serious adverse event (p=0·010). Acute kidney injury occurred more frequently in participants assigned to cloxacillin (15 [12%] of 128) than in those assigned to cefazolin (one [1%] of 134; p=0·0002). INTERPRETATION:Cefazolin constitutes an alternative to cloxacillin for the treatment of MSSA bacteraemia, offering non-inferior clinical efficacy and potentially enhanced tolerability. FUNDING:French Ministry of Health.

This narrative review aims to provide an overview of current knowledge on mpox, emphasizing updated epidemiology and recent advances in treatment and prevention strategies, in light of the latest outbreaks. We searched PubMed and Google Scholar for publications on ‘Mpox’ and ‘Monkeypox’ up to June 5, 2025. Grey literature from governmental and health agencies was also accessed for outbreak reports and guidelines where published evidence was unavailable. Recent outbreaks have redefined mpox epidemiology. Whereas previous regional outbreaks were mainly driven by zoonotic spillover with limited household transmission and often affecting children, more recent outbreaks have involved sustained human-to-human transmission. Such transmission has occurred among men who have sex with men for clade IIb and within heterosexual networks for clade Ib outbreaks, and more recently clade Ia outbreaks, primarily through sexual contact. Clinical features have also shifted toward more localized lesions, prominently in the anogenital area. While mpox is usually self-limited, severe cases may occur in pregnant women, young children, and immunocompromised individuals. Mpox management primarily relies on supportive care. In patients with severe mpox, or at risk of, tecovirimat was widely recognized as the first-line therapy, although it has failed to demonstrate its effectiveness in recent randomized controlled trials. The Modified Vaccinia Ankara vaccine (two-dose regimen) has shown a favorable safety profile and promising efficacy data in preventing clade IIb mpox, including immunocompromised individuals. Mpox has transitioned from a neglected zoonosis to a re-emerging global health threat. Sustained surveillance, robust and targeted public health interventions, and equitable access to diagnostics, vaccines, and antiviral treatments are critical to managing potential future mpox outbreaks.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e33231.].

[This corrects the article DOI: 10.1371/journal.pone.0288845.].

We investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15-0.38], p < 10-9; nucleosomes: aHR 0.62, 95% CI [0.48-0.81], p < 10-3). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65-6.28], p < 10-5). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target.

Overuse of antibiotics is frequent in nursing homes (NHs) leading to adverse events and selection of resistant bacteria. Antimicrobial stewardship interventions showed heterogeneous effects on reducing inappropriate use of antimicrobials in NHs. This study aimed (1) to analyze antimicrobial prescribing determinants in NHs; (2) to identify which resources for antimicrobial prescribing are used by NHs’ physicians (3) understand which antimicrobial stewardship interventions are required and how they should be implemented in NHs. We conducted individual semi-directed interviews with NHs’ prescribing physicians in Ile-de-France, France. A thematic content analysis was conducted iteratively. Thirteen interviews were conducted. Participants were mostly women, with a median age of 48 years and a median professional experience in NHs of three years. Participants included medical coordinators, general practitioners and salaried physicians. Main determinants of antimicrobial prescribing in NHs were the perceived risk of infectious complications and discomfort in residents, the difficulty in obtaining microbiological samples and the lack of healthcare professionals to monitor patients. Most participants reported using national guidelines and electronic decision support systems to guide their antimicrobial prescribing. Institutional constraints accentuate situations of doubt and prompt physicians to prescribe antimicrobials “just in case” despite the will to follow guidelines and the known risks of antimicrobial misuse. Physicians stated that proper antimicrobial use in NHs would require a major effort but was not judged a priority as compared to other medical issues. Producing guidelines tailored to the NH’s context, performing good practice audits with feedback on antimicrobial prescribing, and reinforcing multidisciplinary relationships and discussions between city and hospital professionals were cited as potential interventions. The role of the medical coordinator was described as central. According to physicians, collaboration among stakeholders, providing support and training during the process might prove effective strategies to ensure successful implementation. Antimicrobial prescribing is a complex decision-making process involving different factors and actors in NHs. Tailored guidelines, good practice audits, strengthened multidisciplinary collaboration were proposed as key AMS interventions. Physicians emphasized the central role of the medical coordinator supported by stakeholder engagement, collaboration, training and ongoing support for successful implementation. According to physicians working in French NHs, antimicrobial prescribing in nursing homes depends on the resident’s characteristics, the environmental context and resources, the nursing staff professional role and the perceived consequences of antimicrobial prescribing by the physicians. Nursing home physicians feel quite comfortable with antimicrobial prescribing in everyday situations and may not feel that improving antimicrobial prescribing is a top priority. Developing new guidelines tailored to the nursing homes context, providing audit, feedback on antimicrobial prescribing and straightening multidisciplinary relationships, were perceived by French physicians working in NHs as good leverage to improve antimicrobial prescribing.

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.

Background:Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods:Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results:Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion:hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

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

Background: Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection. Methods: This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48 h. Results: One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one -month mortality were age and maximum oxygen flow during hospitalization. Conclusion: RSV -associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate.