Abstract Background Digital antimicrobial stewardship (AMS) interventions, such as clinical decision support systems, audit-and-feedback platforms, and electronic prescribing tools, have been increasingly adopted to improve antibiotic use. However, the effectiveness of these interventions across healthcare settings remains uncertain, and the certainty of the evidence has not been comprehensively evaluated. The objective of this study was to provide a comprehensive understanding of the role of digital interventions in optimizing antimicrobial use and improving clinical outcomes within a broad spectrum of healthcare settings. Methods We conducted a systematic review and meta-analysis of randomized controlled trials evaluating digital AMS interventions that followed PRISMA 2020 guidelines and registered in PROSPERO (CRD420251178854) and funded by the Wellcome Trust CAMO-Net programme. Searches were performed across major databases. Primary outcomes included the appropriateness of antibiotic prescriptions and the antibiotic prescription rate. Secondary outcomes included 30-day mortality, 30-day hospital readmission, and length of hospital stay (LOS). Random-effects models were used to pool effect sizes. Risk of bias was assessed using RoB 2.0, and certainty of evidence was rated using GRADE. A Summary of Findings table was prepared to present effect estimates, sample sizes, and evidence certainty. Results Eleven RCTs met the inclusion criteria, and nine were included in the quantitative synthesis. Digital AMS interventions did not show a significant effect on appropriateness of antibiotic prescribing (RR 0.99, 95%CI 0.93–1.05; very low certainty). There was no reduction in antibiotic prescription (RR 0.98, 95%CI 0.88–1.09), with substantial statistical heterogeneity (I² = 71%) and very low certainty. Across clinical outcomes, digital AMS showed no effect on 30-day mortality (RR 0.91, 95%CI 0.77–1.09; very low certainty) or 30-day readmission (RR 0.95, 95%CI 0.79–1.14; very low certainty). For LOS, results were inconsistent across studies, and the pooled effect showed no clinically meaningful change (MD 0.17 days, 95%CI –0.01 to 0.35; very low certainty). Most trials had “some concerns” of bias due to deviations from intended interventions. Conclusion Meta-analyses of digital AMS RCTs showed a lack of evidence with a high level of certainty on antibiotic prescribing or clinical outcomes due to high heterogeneity in interventions and study designs, as well as RCTs’ limitations (no adoption/fidelity metrics).

AIMS:Urban aquatic environments are increasingly recognized as important components in the persistence and dissemination of antimicrobial-resistant bacteria. This study investigated the occurrence, antimicrobial resistance profiles, and genomic characteristics of carbapenem-resistant Klebsiella pneumoniae complex isolated from urban rivers in São Caetano do Sul, part of the São Paulo Metropolitan Region, Brazil. METHODS AND RESULTS:Between October 2023 and October 2024, 39 surface water samples were collected from two urban streams and processed using selective culture, MALDI-TOF identification, antimicrobial susceptibility testing, and whole-genome sequencing. Among 144 K. pneumoniae complex isolates recovered, 43 (29.9%) were resistant to meropenem. All meropenem-resistant K. pneumoniae isolates carried the blaKPC gene, while one Klebsiella quasipneumoniae isolate harbored blaNDM. Multilocus sequence typing revealed high genetic diversity, with predominance of global disseminated high-risk lineages, including ST11 and ST258. The repeated detection of identical sequence types across different sampling sites and time points suggests environmental persistence within the urban river network. CONCLUSION:These findings demonstrate that urban surface waters act as reservoirs for clinically relevant carbapenem-resistant Klebsiella lineages, highlighting the importance of environmental surveillance as part of applied strategies to monitor antimicrobial resistance in urban settings.

This study aimed to investigate the microbial community structure and the presence of Antibiotic-Resistant Bacteria (ARB), Antibiotic Resistance Genes (ARGs), and antimicrobial residues in an urban stream adjacent to an informal settlement in Brazil. Water samples collected during the winter of 2021 (n = 7) were analysed using culture-dependent and -independent methods. Microbial community structure was assessed by 16S rRNA sequencing, while bacterial isolates were characterized by Chlorhexidine Minimum Inhibitory Concentration (CHX-MIC) and whole-genome sequencing. Free carbapenemase ARGs were screened by conventional PCR and selected antimicrobial residues were quantified by UHPLC-MS/MS. The bacterial community was dominated by phyla Firmicutes, Bacteroidota, Proteobacteria, Campylobacterota, Actinobacteriota, and Patescibacteria. Abundant (> 5%) families included Ruminococcaceae, Prevotellaceae, Moraxellaceae, and Arcobacteraceae, associated with faecal contamination and antimicrobial resistance. Urban stream bacterial isolates (31/66) belonged mainly to the genera Aeromonas, Citrobacter, Escherichia, Serratia, Chryseobacterium, Elizabethkingia with a high percentage of phenotypic resistance to third-generation cephalosporin and carbapenems. WGS of some isolates (16/31) revealed the co-production of ESBL and carbapenemase ARGs as well as Inc-type plasmids, efflux pumps and virulence genes. CHX-MICs ranged from 0.5 to 128 mg/L, with Klebsiella pneumoniae and Serratia marcescens showing the highest values and harboring qac genes and IncHI2 plasmids, respectively. Azithromycin, ceftriaxone, levofloxacin, and chlorhexidine were detected at up to 2.39, 1.18, 0.14, and 0.43 mg/L, respectively. Notably, ceftriaxone-positive water samples also contained ARB and free ARGs (blaNDM, blaKPC, blaVIM). These findings highlight urban streams as reservoirs of ARB, ARGs, and antimicrobial residues, stressing the urgent need for local water treatment to mitigate antimicrobial resistance and public health risks.

This work aims to investigate the strengths and limitations of non-invasive audio-based deep learning methods for the detection of respiratory conditions. We contrast the performance obtained in tasks such as the expert-centered respiratory insufficiency (RI) detection with easily measured blood oxygen saturation (SpO2) estimation. Several deep learning audio models have been recently proposed for RI detection via voice and speech analysis; these models have obtained an accuracy of 95% in general patients and 97.4% in COVID-19 patients. Here, we extend those results, refining several pretrained audio neural networks (CNN6, CNN10 and CNN14) and Masked Autoencoders (Audio-MAE) for RI detection, showing that some of these models achieve near perfect accuracy (99.9% on COVID RI and 98.6% on general RI). The models were pretrained on AudioSet resulting in improved performance, with transfer learning playing a key role in the prevention of overfitting. The near-perfect RI detection performance suggests that low-cost and automated methods could be developed for assisting patient triage. In parallel, this paper seeks to verify SpO2 estimation feasibility, so we perform a 92% SpO2-threshold binary classification using the same architectures. In contrast to our findings for RI, this model yielded an accuracy below 70% and MCC-correlation below 0.3, indicating both that SpO2 estimation solely from audio is unfeasible and the presence of multiple features in the audios which are useful for RI detection, but not for SpO2 estimation. We propose that this discrepancy demonstrates the limits of voice and speech biomarkers across different diagnostic tasks under current technologies.

Central line-associated bloodstream infection prevention remains challenging in clinical settings. This experience describes how barriers identified through a needs assessment in Brazilian hospitals were translated into a tailored serious game to support catheter care practices. Using the Octalysis Framework, real-world challenges were converted into interactive missions simulating catheter care. This approach illustrates how context-specific barriers can be operationalized into an educational tool to support health care workers' adherence to central line-associated bloodstream infection prevention measures.

Introduction/Objectives Despite widespread antifungal use in Primary Health Care (PHC), data on prescription patterns remain scarce. This study investigated the prevalence of mycoses in PHC in a Brazilian city, the antifungal treatments prescribed, and their appropriateness. Methods Descriptive study based on PHC electronic medical records, analyzed with support from a data science team. Conducted in the 12 PHC units of São Caetano do Sul, Brazil, from January to September 2023. Results There were 224,157 medical visits, of which 982 (0.44%) reported mycoses, identified via ICD-10 and/or ICPC-2 codes. Most patients were male (n = 692; 70%), with median age 50 years (IQR 31–66). Most frequent diagnoses were candidiasis (n = 355; 36.2%) and dermatophytoses (n = 343; 34.9%), followed by unspecified mycoses (n = 220; 22.4%). Of 4,533 antifungal prescriptions (3,271 topical; 1,262 oral), only 23% were issued to patients with a recorded mycosis diagnosis. The most prescribed topical antifungal for mycoses was ketoconazole (42.5%, n = 1,389), followed by nystatin (24.8%, n = 812) and miconazole (14.3%, n = 468). In 344 cases (10.5%), topical antifungals were combined with corticosteroids and/or antibiotics. Among oral antifungals, fluconazole was most prescribed for mycoses (89.3%, n = 1,127), followed by itraconazole (5.9%, n = 75) and terbinafine (4.8%, n = 60). Combined therapy with topical and/or oral antifungals was observed in 775 visits (21.1%), most commonly for candidiasis and dermatophytoses; 693 visits involved two antifungals and 82 involved three, with fluconazole plus nystatin being the most frequent combination. Among cases with a recorded mycosis diagnosis, prescription appropriateness was 100% for candidiasis, pityriasis versicolor, and sporotrichosis, and 98% for dermatophytoses. Conclusion Most prescriptions were topical azoles, and a large share (77%) was provided to patients without a documented mycosis diagnosis, possibly due to use of nonspecific ICD-10 codes by prescribers.

BACKGROUND:Antimicrobial stewardship programmes (ASPs) are essential to tackling antimicrobial resistance, particularly in primary care, where most prescribing occurs. Pharmacists play a key role in ASPs through patient education, prescription monitoring, and promoting appropriate use. This study assessed the status of ASPs in primary healthcare centres (PHCs) in São Paulo state from the pharmacists' perspective. METHODS:A cross-sectional survey was conducted between June 2023 and January 2024 among pharmacists working in PHCs across São Paulo. The questionnaire, based on CDC and ANVISA guidelines, addressed demographics, PHC characteristics, ASP activities, and pharmaceutical interventions. Descriptive statistics were used. RESULTS:Of 201 responses, 189 were eligible, representing PHCs in 68 cities. Most pharmacists (75%) had postgraduate education, and 70% worked in centres serving over 500 patients. Although 79% of PHCs used electronic medical records, only 32% had written ASP policies and 29% monitored antimicrobial use. Diagnostic resources were limited; respiratory virus tests were the most available (43%). Educational activities on antimicrobial use occurred in 26% of PHCs. Pharmaceutical interventions were reported by 77% of pharmacists, mainly related to dosage (54%) and treatment duration (25%), with high prescriber acceptance (≥80% in 34% of cases). CONCLUSIONS:This study identified strengths and gaps in ASP implementation across PHCs. While improvements were seen in infrastructure and pharmacist training, key limitations remain in policy development, diagnostics, prescriber support, and public education. We recommend: (1) establishing local ASP policies, (2) expanding access to rapid diagnostics, (3) continuing education for prescribers and pharmacists, and (4) public awareness campaigns tailored to primary care.

Background The Centres for Antimicrobial Optimization Network Brazil aims to implement an antimicrobial stewardship program in Brazilian municipality. This study explores barriers and enablers to its implementation, through understanding the context and beliefs regarding antimicrobial use in this environment. Methods The study occurred in 12 primary health care units, where a mixed-method study was conducted. A total of 208 out of 450 health care workers completed a Theoretical Domain Framework-based survey, and 16 patients and 12 health workers were interviewed. Survey results were compared by professional category; interviews were analyzed using Critical Discourse Analysis. Results Professionals with higher education scored higher across most domains. In the “Optimism” domain, these professionals scored ≥6.0, while others scored ≤5.0. Similar patterns were observed in the domains “Knowledge” (≥6.0 vs ≤5.5), “Social/professional role and identity” (≥6.36 vs ≤5.79), and “Intentions” (≥6.0 vs ≤5.0). Qualitative data highlighted breaks in the continuity of care and gaps in patient knowledge about antimicrobial use. Key barriers included disparities in training, physician-centered decision-making, and patient knowledge gaps. Enablers included health care workers' willingness to learn and home caregivers' understanding of patient conditions. Conclusions The implementation of the antimicrobial stewardship program depends on addressing training disparities and leveraging health care workers' willingness to learn.

PURPOSE:To evaluate in vitro efficacy of amikacin combined with meropenem, colistin, and ceftazidime/avibactam against diverse multidrug-resistant isolates of K. pneumoniae (n = 40), A. baumannii (n = 20), and S. marcescens (n = 12), using three methods. METHODS:Antimicrobial combinations were tested via Epsilometer strip crossing, disk approximation, and time-kill assays. RESULTS:Amikacin combined with colistin and ceftazidime/avibactam showed synergy in 70,0 % (28/40) and 75,0 % (9/12) of K. pneumoniae and S. marcescens isolates. Meropenem showed limited activity in 25,0 % (5/20) of A. baumannii isolates. Minor errors were observed in <50,0 % of isolates, notably with a 25,0 % error rate for amikacin and colistin using disk approximation. Presence of aminoglycoside-modifying enzyme (AMEs) and blaOXA-23 genes in A. baumannii, and AMEs and ESBL genes in Enterobacterales showed low synergy. CONCLUSION:Amikacin combined with colistin and ceftazidime/avibactam showed promise against Enterobacterales MDR infections but limited efficacy against Acinetobacter, influenced by resistance genes. E-test can be useful for routine laboratory.

In 2016-2019, Brazil faced the most important yellow fever (YF) outbreak in recent decades. In 2019, cases were concentrated in Ribeira Valley, in the southeast region of Brazil, and largely affected rural Quilombola communities, which can trace their origins to escaped, freed, or abandoned slaves in the mid-1800s, and which traditionally practice subsistence agriculture. We aimed to explore aspects of the YF outbreak and vaccination from the perspective of the Quilombola communities. This was a cross-sectional descriptive study conducted in two Quilombola communities in Ribeira Valley (Sapatu and Nhunguara), using an interviewer-administered questionnaire that included both closed and open-ended questions. Thematic reflective analysis principles were applied for qualitative analysis. We adopted a theoretical domains framework to identify and categorize reported facilitators and barriers to YF vaccination. A total of 226 participants were enrolled: 46% male, median age 44 years. Eighty participants reported acute illness during the outbreak; fever, headache, myalgia, and nausea were the most common symptoms. Only eight participants reported laboratory-confirmed YF. Almost all participants (96.5%) reported YF vaccination. Less than two-thirds of the participants were vaccinated before the first case in the Ribeira Valley; over a third were vaccinated after the death of a community leader. The themes were: concerns about the vaccine, difficulty in accessing healthcare, perception of disease risk, knowledge about disease severity, cultural beliefs, and influence of leaders. The outbreak in the Ribeira Valley may have been averted with an understanding of the vaccination decision-making process, influenced by individual, sociocultural, and contextual factors.

BACKGROUND:The implementation of an innovative form of personal protective equipment (PPE) as an infection and prevention control measure for respiratory transmissible diseases is complex, with several elements to be addressed. AIM:To make considerations for integrated face and respiratory protection implementation in clinical settings. METHODS:This was a multi-site qualitative study with 87 health workers that compared traditional PPE or powered air-purifying (PAPR) respirators with lightweight PAPR (L-PAPR). Semi-structured interviews were performed based on the Consolidated Framework for Implementation Research (CFIR). FINDINGS:Insights into L-PAPR implementation were found. The advantages include enhanced sense of protection, pleasant ventilation, good visibility for both health worker and patient, no fogging of the visor interior, no movement restriction, and easy disinfection process. To enhance usability some barriers should be tackled: reduction of facial pressure; better accommodation for glasses and corrective lenses; reduction of number of steps for assembling the device; infrastructure provision for storage, charging and disinfection of the device; training of health workers for assembling, donning and doffing; and the cost benefit of implementation. CONCLUSION:L-PAPR was overall perceived with advantages by many participants, and can be considered a potential option of PPE to be implemented to protect health workers during outbreaks of respiratory transmissible diseases.

BACKGROUND:Exploring records from entire cities to make decisions, particularly within public health systems, remains challenging. METHODS:This study investigates the public health data of São Caetano do Sul (SCS), in Brazil, to uncover patterns of antimicrobial prescriptions for infectious diseases using electronic health system records from primary care. Data science techniques such as preprocessing, transformation, loading, and analytics were also applied to achieve this goal. RESULTS:From January to September 2023, a total of 575,616 records of medical appointments were analyzed, and 67,023 patients underwent one or more medical appointments of which 16,572 had infectious diagnoses. There were 7,938 prescriptions of antimicrobials for infections of which the most frequent were upper respiratory infections (37%), gingivitis/periodontal disease (20%), and urinary tract infections (9%). The most frequently prescribed antimicrobials were amoxicillin (23%), azithromycin (15%), amoxicillin/clavulanate (13%), ciprofloxacin (11%), and cephalexin (11%). A preliminary evaluation of the data highlighted several points for targeted interventions, as well as challenges in obtaining certain information. For instance, some infections lacked documented antimicrobial treatment, while others were managed with medications not considered first-line options. CONCLUSION:Implementing a system that can extract data directly from electronic records and automatically present it in a logical and relevant way to health professionals-including policymakers and administrators-would enable the identification of potential problems, the planning of interventions to improve antimicrobial use, and the monitoring of their impact. Our findings highlight opportunities to improve antimicrobial prescribing through data-driven tracking, analysis, and feedback mechanisms.

Previous cross-sectional transcriptomics studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at the time of biopsy; however, longitudinal data are scarce. We utilized clinical follow-up data up to five years post-biopsy, linking the transcriptomes of diagnostic kidney biopsies to progression rates and outcomes in 19 patients with DKD. Patients were stratified into “rapid progressors” and “non-rapid progressors” based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite outcome of kidney failure or 40

Methicillin-Resistant Staphylococcus Aureus (MRSA) is commonly transmitted among hospitalized patients through direct contact or contaminated objects. However, the dynamics of household transmission of MRSA remain unclear, posing challenges for effective prevention. This study evaluates the persistence of MRSA colonization in asymptomatic carriers over a period of at least 17-months and examines the potential for intra-household transmission. We conducted home visits to seven families, each with at least one MRSA-colonized member, to collect nasal swabs from all household members. Phenotypic and genotypic profiles of the isolates were determined through culture, antimicrobial susceptibility testing, and PCR. We compared these new samples with previous samples from a recent study involving the same individuals to assess spontaneous clearance of MRSA. A total of 25 samples were collected, with 56 % (14) identified as S. aureus and 44 % (11) as non-S. aureus; among the S. aureus isolates, four were MRSA. We observed spontaneous clearance of MRSA in six of the original cases. Unexpectedly, there was limited intra-household transmission of MRSA, although all families with MRSA colonization had at least one member with a history of skin disease. In the family where colonization persisted, one individual had recurrent cutaneous abscesses, suggesting a possible link to sustained colonization.

BACKGROUND:Survivors of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia endure complex hospitalizations; their perspectives remain underexplored. METHODS:We conducted a qualitative study at a tertiary hospital. Survivors (≥18 years) of CRAB bloodstream infection from 2019 to 2024, discharged ≥6 months, were invited to narrative video-call interviews. Interviews were analyzed using critical discourse analysis (CDA) to examine meanings around hospitalization, health care communication, and understanding of resistant bacteria. RESULTS:Nine participants were interviewed. Narratives revealed: (1) hospitalization process and aftermath---profound emotional distress, physical limitations, and long-lasting consequences, with comparisons of life "before" and "after"; (2) barriers in patient-professional communication---limited or absent explanations about procedures, invasive devices, or the infection itself, leading to feelings of alienation and lack of autonomy; and (3) understanding of antibiotic-resistant bacteria---none could define multi-drug resistance, several were unaware of their CRAB diagnosis. Even patients with high health literacy (eg, HIV, aspergillosis, or CMV) did not recall adequate information about antibiotic resistance, underscoring systemic communication gaps. DISCUSSION:Encouraging patient involvement in infection prevention (eg, reminding staff about hand-hygiene) is promising but underused. Participants sometimes feared adverse reactions when speaking up. CONCLUSION:Structured healthcare-associated infections (HAIs) education with patient participation in hand-hygiene reminders is a feasible, patient-centered approach that may improve understanding and shared safety. Implementation could use scripted bedside prompts and brief teach-back, supported by plain-language leaflets and bedside posters co-designed with patients.

Antimicrobial resistance (AMR) is a global health challenge that threatens humans, animals and the environment. Evidence is emerging for a role of healthcare infrastructure, environments and patient pathways in promoting and maintaining AMR via direct and indirect mechanisms. Advances in vaccination and monoclonal antibody therapies together with integrated surveillance, rapid diagnostics, targeted antimicrobial therapy and infection control measures offer opportunities to address healthcare-associated AMR risks more effectively. Additionally, innovations in artificial intelligence, data linkage and intelligent systems can be used to better predict and reduce AMR and improve healthcare resilience. In this Review, we examine the mechanisms by which healthcare functions as a driver, reservoir and amplifier of AMR, contextualized within a One Health framework. We also explore the opportunities and innovative solutions that can be used to combat AMR throughout the patient journey. We provide a perspective on the current evidence for the effectiveness of interventions designed to mitigate healthcare-associated AMR and promote healthcare resilience within high-income and resource-limited settings, as well as the challenges associated with their implementation. In this Review, Holmes and colleagues explore the mechanisms by which healthcare functions as a driver, reservoir and amplifier of antimicrobial resistance (AMR), and they explore opportunities and innovative solutions to mitigate healthcare-associated AMR and promote healthcare resilience.

AimLanguage difficulties in children can have enduring impacts on their academic and emotional well-being. Consequently, early identification and intervention are critical. This study aimed to investigate the impact of introducing Sprakfyran, a language screening tool, on the identification and referral rates for speech and language assessment compared to the previous method.MethodsAn observational study was conducted in Gotland, Sweden, using the medical records of 3537 children (53% boys) who were 3-4 years of age. The study period lasted between 5 January 2016 and 29 April 2022, encompassing data collection both before and after the introduction of Sprakfyran.ResultsFollowing the introduction of Sprakfyran, 15% failed the screening, compared to 20% with the previous speech test. However, referrals for assessment increased significantly with Sprakfyran, rising to 7% compared to 3% with the speech test.ConclusionThe proportion of children who failed the Sprakfyran screening was consistent with findings from previous studies. Children who failed the screening were more likely to be referred for speech and language assessment after the introduction of Sprakfyran. This indicates that Sprakfyran is a clinically relevant tool that promotes children's language development through increased referral rates.

ABSTRACT Backgrounds: Fortunately, much has been studied about COVID-19 in patients with inflammatory bowel diseases (IBD). Evidence suggests that these patients do not appear to be at increased risk of severe COVID-19. However, there are still some uncertainties regarding the clinical manifestations of COVID-19 in patients with immune-mediated diseases. Objective: This study aimed to describe the main symptoms of COVID-19 and their frequency in IBD patients and evaluate the impact of the IBD therapeutic drugs on clinical presentation of COVID-19 and to determine factors associated with COVID-19 in this population. Methods: Adult patients with IBD from three tertiary-care public, teaching hospitals in Ceará, Northeastern Brazil, were evaluated during one scheduled appointment from March to December 2020. Patients with possible or confirmed COVID-19 were compared with patients without COVID-19. Furthermore, incidences of each symptom were evaluated based on the use of IBD therapeutic drugs. Results: A total of 515 patients with IBD were included in the study: 234 with CD, and 281 with UC. Of these, 174 patients (34%) had possible/confirmed COVID-19 of whom 156 (90%) were symptomatic. Main symptoms were fever (65%) and headache (65%); gastrointestinal symptoms occurred in one third of patients and were higher than COVID-19 in general population. The factors associated with having COVID-19 were female gender (OR 1.71, 95%CI: 1.17-2.50); contact at home (OR 5.07, 95%CI: 3.31-7.78) and outside the home (OR 3.14, 95%CI: 2.10-4.71) with a case of COVID-19; work outside of the home (OR 1.87, 95%CI: 1.26-2.78); family history of COVID-19 (OR 2.29, 95%CI 1.58-3.33) use of salicylate (OR 1.71, 95%CI: 1.17-4.28); and asthma (OR 7.10, 95%CI: 1.46-34.57). Conclusion: IBD patients at high risk of COVID-19 infection may need to avoid salicylate therapy but further studies are necessary to confirm this association.