Antimicrobial Resistance & Infection Control

Objectives- Among clinical methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) strains, we sought to determine the prevalence of {beta}-lactam-{beta}-lactamase inhibitor (BLBLI) susceptibility, and its association with oxacillin susceptibility, genotypic factors, and patient characteristics. Methods- Clinical MRSA BSI strains were tested for susceptibility to penicillin-clavulanate by Etest (n=117, 36% of the dataset) and to oxacillin by disk diffusion assay (n=328, 100%). Penicillin-clavulanate susceptibility was defined as MIC [≤]2mg/L and oxacillin disk susceptibility as an inhibition zone > 6mm. All strains were whole-genome sequenced, and alleles of mecA annotated. The sensitivity and specificity of the oxacillin disk to predict penicillin-clavulanate 'susceptibility' were assessed. Clinical and genomic associations with BLBLI 'susceptibility' were assessed by calculating odds-ratios (OR). Results -We found 73/117 (62%) and 205/328 (62%) strains to be 'susceptible' to penicillin-clavulanate and oxacillin disk, respectively. Oxacillin disk susceptibility and penicillin-clavulanate susceptibility were highly correlated (sensitivity 97.3% and specificity 95.5%). We therefore used oxacillin disk susceptibility as a proxy for penicillin-clavulanate susceptibility. Comparative genomics of the mecA gene uncovered 8 alleles. The oxacillin disk 'susceptible' phenotype was associated with specific mecA alleles, community-associated MRSA sequence-types (OR 72.8, 95%CI 35.4-162), community acquisition of infection (OR 2.09, 95% CI 1.03-4.27), lower Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.98) and SOFA (sequential organ failure assessment) scores at presentation (OR 0.88, 95% CI 0.79-0.98). Conclusion - BLBLI 'susceptibility' is common among MRSA strains and is strongly associated with the strain genotype. Infections caused by BLBLI 'susceptible' strains are associated with specific patients' characteristics, namely younger age, fewer comorbidities, acquisition in the community and milder presentations.

Importance: Antibiotic-resistant infections in neonates often arise from the infant's own colonizing bacteria harboring antibiotic resistance genes (ARG). This study evaluates ARG that impact antibiotic selection and drive resistance-related mortality, termed clinically important antibiotic resistance genes (CI-ARG). Objective: To determine differences in gut CI-ARG abundance in children from birth through 3 years old, stratified by neonatal intensive care unit (NICU) admission and antibiotic (abx) exposure in the first two months Design: Cohort study (sequencing, analysis completed 2025-2026) using shotgun metagenomic sequencing of stool samples from infants in two studies: Neonatal Intestinal Microbiome (+NICU groups, 2015-2022), The First 1000 Days of Life and Beyond (-NICU groups, 2018-2021). Infants grouped into four cohorts: +NICU/+abx, +NICU/-abx, -NICU/-abx, and -NICU/+abx. Prespecified CI-ARG abundance compared longitudinally among groups. Setting: NICU, well-baby nursery, Inova Fairfax Hospital, Virginia Participants: +NICU criteria: admission to the NICU, anticipated length of stay (LOS) of at least five days, maternal age at least 18 years. -NICU: parents with good general health and age at least 18 years enrolled prior to infant birth. Stool samples: adequate stool processing volume, at least one stool sample from before one month and after one year of age, 7-day minimum between serial samples. Exposures: NICU versus well-baby nursery; antibiotics versus none in first two months of corrected age Main Outcomes and Measures: Predefined primary outcome- longitudinal CI-ARG abundance by group, compared using linear mixed effects models with adjustment for multiple comparisons (Benjamini-Hochberg procedure). Predefined secondary outcomes- differences in overall microbiota and resistome composition. Results: 1000 serial stool samples, 179 infants (birth-39 months). Longitudinal abundance significantly differed among cohorts for 11 CI-ARG (p < 0.05); often higher in the +NICU groups in early life, with or without antibiotic exposure. Abundance of ARG conferring resistance to aminoglycosides, macrolides, and fluoroquinolones later decreased below -NICU levels. mecA, which often drives methicillin resistance in Staphylococcus, was detected only in +NICU infants during premature period. Conclusions: This longitudinal study demonstrates significant longitudinal CI-ARG differences in children grouped by early-life NICU status and/or antibiotic exposure. Future studies should explore the mechanisms driving these CI-ARG changes and evaluate their impact on infection risk and community spread.

Background Hand hygiene is the most effective and cost-efficient measure for preventing healthcare-associated infections (HAIs). However, adherence among healthcare workers remains suboptimal, particularly in low-resource settings. Purpose/Aim This study assessed the level of adherence to hand hygiene practices and the factors associated with adherence among healthcare workers at Lubaga Hospital, Kampala City. Methods An analytical cross-sectional study was conducted among 216 healthcare workers selected using stratified random sampling. Data were collected through direct observation using the WHO "Five Moments for Hand Hygiene" checklist and a structured, self-administered questionnaire. Data were analyzed using SPSS version 20. Descriptive statistics were used to summarize the data, while inferential analysis included Pearsons Chi-square tests and Modified Poisson regression to estimate crude and adjusted prevalence ratios (cPR and aPR) with 95% confidence intervals at a significance level of p [&le;]0.05. Results Overall adherence to hand hygiene practices was 69.9%, while 30.1% of participants were non-adherent. At the individual level, gender, cadre, and attitude toward hand hygiene were significantly associated with adherence. Male healthcare workers were less likely to adhere compared to females (aPR = 0.490, 95% CI: 0.226-0.969), while nurses and midwives were more than twice as likely to adhere compared to other cadres (aPR = 2.213, 95% CI: 1.113-4.398). Participants with a positive attitude toward hand hygiene were also significantly more likely to adhere (aPR = 1.462, 95% CI: 1.227-3.226). Resource-related factors, including the availability of alcohol-based hand rub and timely replenishment of supplies, were not significantly associated with adherence. Organizational factors such as recent training in hand hygiene and infection prevention (aPR = 1.771, 95% CI: 1.673-2.989), presence of reminders (aPR = 1.747, 95% CI: 1.538-5.949), feedback on performance (aPR = 0.339, 95% CI: 0.156-0.738), and teamwork (aPR = 3.006, 95% CI: 1.424-6.348) were significantly associated with improved adherence. Conclusion Adherence to hand hygiene practices among healthcare workers was moderate but remains suboptimal. Behavioral and organizational factors, particularly training, feedback, teamwork, and attitude, play a more significant role in influencing and adherence than resource availability alone.

Background. Genomic surveillance of Gram-negative pathogens is generally selective, focusing on suspected outbreaks or resistant isolates. The extent of what such programmes miss remains unknown. It has not been quantified in a large, unselected dataset. Methods. We prospectively whole-genome sequenced isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from two tertiary-care hospitals in Copenhagen and Hannover, regardless of resistance phenotype, specimen type, or ward. We analysed 25,888 genomes from 13,712 patients. Clonal clusters were defined by single-linkage clustering at [&le;]30 SNPs, based on within-patient distances and validated against inpatient movement records. Analyses were patient-based, with hospital comparisons using matched 18-month periods. Results. Clonal clusters included 14.1% of patients in Copenhagen and 16.5% in Hannover. Most clustered patients had no multidrug-resistant isolate (71.3% and 50.0%) and had no intensive care unit (ICU)-associated isolate (86.1% and 68.7%). Sequencing blood-culture isolates alone, the usual trigger for genomic investigation, would have identified only 14 of 900 clustered patients in Hannover (1.6%). Excluding colonisation screening would have missed 240 (26.7%). No targeted strategy detected more clustered patients than random sampling of the same number of isolates. Detection increased with sequencing effort without reaching a plateau. After matching periods and adjusting for ICU association, resistance, and specimen mix, clustering remained more common in Hannover (adjusted odds ratio 1.49, 95% CI 1.28-1.73), suggesting sampling explained much, but not all, of the difference. Conclusions. Most Gram-negative clusters involved non-MDR organisms on general wards and would have been missed by surveillance focused on resistance or intensive care. What is selected determines which patients can be detected; the number of isolates sequenced determines how many are found. The observed 14-16% is a lower bound. Surveillance should sample broadly and representatively, and report what was sequenced and how much.

Background Using a population-based cohort from the Calgary Health Zone (CHZ), Canada, we integrated longitudinal antimicrobial susceptibility and prescribing data with the whole genome sequences of five major pathogens. We aimed to assess how antimicrobial resistance (AMR) responds to prescribing changes and determine which bacterial strains shape these dynamics. Methods We analysed antibiotic prescribing rates, clinical and genomic data from 7,271 Staphylococcus aureus, 1,609 Enterococcus faecalis, 801 Enterococcus faecium, 11,363 Escherichia coli, and 2,319 Klebsiella pneumoniae isolates, associated with bacteraemia episodes in the CHZ between 2006-2022. Genomic clusters (referred to as strains) were identified using StrainGST and assigned to known sequence types (STs) or clonal complexes (CCs). Strain-level incidence, stratified by community-onset (isolates collected [&le;]48h after admission) and hospital-onset (>48h after admission), AMR phenotypes, and prescribing rates were modelled using negative-binomial and binomial regression. Temporal trends were quantified using average annual percentage change (AAPC). Findings Between 2010-2022, fluoroquinolone prescribing declined in both community (AAPC=-6.8% [95% CI -8.1, -5.4]; p<0.0001) and hospital settings (AAPC=-5.1% [-6.5, -3.7]; p<0.0001). This was accompanied by a significant reduction in fluoroquinolone resistance among Gram-positive species. Specifically, S aureus bacteraemia resistant to clinically important antibiotics, cloxacillin, ciprofloxacin, erythromycin, and clindamycin, declined from 2006 to 2022, mostly in hospital-onset cases (AAPC=-16.0%, [-19.3%, -12.7%], p<0.0001). In E coli, ceftriaxone and ciprofloxacin resistance were clustered in ST131 and the emerging ST1193; the latter increased steadily, particularly in community-onset cases (AAPC=17.7%, [0.0%, 30.0%], p<0.0001). CTX-M-27-producing E coli ST131 strains increased (AAPC=23.8%, [17.4%, 30.5%], p<0.0001) between 20082022, while CTX-M-14-producing E coli ST131 declined (AAPC=-15.9%, [-21.3%, -10.2%], p<0.0001) between 2013-2022. These trends were paralleled by an increase in community cephalosporin prescribing (AAPC=7.3%, [4.2%, 10.5%], p<0.0001) between 2010-2022. For K pneumoniae, hypervirulent ST23 was most common (N=88) with an increasing trend in incidence (AAPC=3.0%, [-2.8%, 9.2%]) between 2006-2019. Conclusions The contrasting resistance trends between Gram-positive and Gram-negative species underscore the complexity of AMR control efforts. Effective strategies will require stewardship efforts targeting multiple drug classes, genomic surveillance for emerging resistant strains, and interventions extending beyond hospital settings.

Objectives To characterise COVID-19 inpatients with and without bacterial/fungal preceding, co- and secondary infections, and describe the distribution of organisms associated with COVID-19 and antibiotic use. Methods We linked ISARIC/WHO CCP-UK data from hospitals in England (admissions 01/01/2020-18/10/2021) with UK Health Security Agency infections datasets of COVID-19, and bacterial- and fungal-positive specimens using a multi-step hierarchical algorithm. We retained those aged >18 years and categorised COVID-19-associated infection as preceding (2-28 days prior to SARS-CoV-2 PCR positive date), co-infection ({+/-}1 day) or secondary (2-28 days after). Results During the study period, there were 173,947 hospitalised episodes of COVID-19; 5.8% (n=10,017) with a bacterial or fungal preceding, co- or secondary infection. Preceding and co-infections were rare (preceding: 0.7%; co-infection: 1.5%) while secondary infections were more common (3.5%). Escherichia coli (29.6%) and Staphylococcus aureus (15.2%) were the most identified organisms in blood specimens, while S. aureus (22.9%) and Pseudomonas aeruginosa (20.4%) were most common in lower respiratory tract specimens. The 28-day case fatality rate (CFR) remained static (36%) in those with secondary infection, whereas it decreased between early 2020 and mid-2021 in the other infection groups (37% to 27%). Of those with no positive microbiology, 72.8% received antibiotics, though this decreased between January-June 2020 (77.6%) and April-October 2021 (62.6%). Conclusion Bacterial and fungal infections complicated approximately 1-in-17 hospitalised episodes of COVID-19, with CFR of >25%. Antibiotic prescribing was common in those without firm evidence of bacterial infection. We recommend adhering to NICE guidance which discourages empirical antibiotic use for hospitalised COVID-19 patients.

Background Surgical site infections (SSIs) are an alarming threat in the surgical field worldwide. They are among the prevalent Hospital Acquired Infections (HAIs) and contribute to antibiotic resistance in resource-limited countries, including Tanzania, where paucity of data exists. This study aimed to ascertain the five-year trend of SSI in Tanzanian health facilities. Methods A retrospective descriptive cross-sectional study was conducted using SSI data reported in the District Health Information System-2 (DHIS2) between October 2021 and December 2025. Data from 138 health facilities were extracted, cleaned, and analysed in R (version 4.5.0). Trends in SSI rates were assessed using Ordinary Least Squares (OLS) regression, with significant variations measured at [&le;] 0.05. Results The 138 facilities reported 419,412 surgical procedures during the study period. Most facilities were primary-level (96, 69.6%) and government-owned (119, 86.2%). The number of reporting facilities increased from 17 in 2021 to 138 in 2025, with an increase in surgical procedures from 9,616 to 127,039. Overall SSI rates declined from 3.1% in 2021 to 2.4% in 2025. Primary-level facilities had the highest overall SSI rate (5.4%), declining from 4.7% to 4.0%. In contrast, SSI following section increased from 1.8% to 2.0%. Organ/space SSI showed a statistically significant declining trend from 1.2% to 0.3% (slope = -0.23%/year; 95% CI: -0.34 to -0.12; p = 0.006). The trends in overall SSI rates by level of health facility and ownership were not statistically significant Conclusion Between 2021 and 2025, overall SSI rates decreased despite a substantial increase in surgical volume, suggesting improvement in IPC. While an organ/space SSI significantly decreased, SSI rates due to caesarean section persistently increased, with higher rates reported in primary healthcare facilities, highlighting the need for strengthened perioperative IPC measures in obstetric care and SSI surveillance across primary-level facilities.

Background Carbapenem-resistant bacteria are a major global public health threat, classified as critical priority pathogens by the WHO. In Indonesia, despite a national antimicrobial resistance control programme established by the Ministry of Health in 2015, resistance rates continue to rise, including increasing carbapenem resistance among clinically important bacteria. Strengthening approaches to directly interrupt transmission is essential, yet transmission pathways remain poorly understood with limited research and policy guidance within the Indonesian context. Methods and analysis The INTERCEPT study is a UK-Indonesia multidisciplinary collaboration aiming to identify transmission routes of carbapenem-resistant bacteria across healthcare and community settings, and the mechanisms of resistance gene transfer between bacteria and mobile genetic elementss. We will conduct genomic surveillance of hospital inpatients, healthcare workers, hospital environments, and surrounding communities, including wastewater systems, combined with genomic analyses and mathematical transmission modelling. A cohort of patients with bloodstream infections will be recruited to evaluate resistant bacteria, treatment practices, and clinical outcomes. Qualitative research will explore behavioural and system-level factors influencing transmission and intervention implementation. Findings will inform stakeholder workshops to co-design context-specific interventions, with pilot intervention over 9 months with pre- and post-intervention assessment to guide scalable strategies to reduce AMR transmission. Discussion The INTERCEPT study addresses carbapenem resistance in Indonesia using an integrated approach combining microbiological surveillance, genomics, modelling, and qualitative methods. Strengths include cross-sectoral analysis (patients, workers, environment) and participatory intervention design. Limitations include geographic scope restricted to Central Java, Indonesia.

Background We examined whether two key housing quality indicators, energy efficiency and household overcrowding, were associated with lower respiratory tract infection (LRTI) hospital admissions in infants. Methods We used a cohort of all singleton births in Scotland 2010-2012, created through linked vital statistics and health data. LRTI admissions were characterised in hospital records. Overcrowding (defined using the national room standard) and median postcode-level energy efficiency were defined using maternal Census and postcode-level Energy Performance Certificate data linked to the cohort, respectively. We used logistic regression to model the odds of at least one infant LRTI admission. Results The cohort included 136,123 infants of whom 4.0% had at least one LRTI admission. Overcrowding was more common among infants of younger mothers and those in rented housing. Energy efficiency was lower among infants of older mothers, living in owner occupied homes, in less deprived areas. Compared with infants living in homes with excess rooms (under-occupied housing), those whose homes were below, or met, the minimum room standard had higher odds of LRTI admission (adjusted odds ratio 1.07, 95% CI 0.98-1.17; 1.10, 95% CI 1.03-1.17, respectively). Postcode-level energy efficiency was not associated with LRTI admission odds. Conclusion Overcrowding was more common in socioeconomically disadvantaged households and associated with increased risk of LRTI admission in infancy. Lower energy efficiency was associated with factors commonly linked to socioeconomic advantage and was not associated with LRTI admissions. Improving access to housing with adequate living space may reduce the burden of LRTIs in early life.

Background: Half of US children are prescribed an antibiotic by age 2. Maternal education and socio-economic factors influence prescribing but the role of other factors, such as age of solid food introduction is unknown. Objectives: We assessed risk factors for time to first antibiotic use between birth to age 2 to identify modifiable drivers of antibiotic use. Methods: We analyzed interviews from mothers of 1032 children participating in the mother-child Center for Oral Health Research in Appalachia cohort 2 between 2011 and 2017. The cohort enrolled healthy, English-speaking, pregnant White women > 18 years with singleton pregnancies. We used time-to-event analyses and a Cox Proportional Hazards model to describe and estimate hazard ratios (HRs) for time to first antibiotic. Results: By age 2, 78% of children received at least one antibiotic (median age at first antibiotic: 12.5 months). Over half (58%) of antibiotics prescribed were for ear infections. After adjustment for household income and birth quarter as fixed variables, time of solid food introduction (aHR: 4.75; 95% CI: 3.19, 7.07), time of first ear infection (aHR: 3.28; 95% CI: 2.58,4.17), and time of first illness (aHR: 4.60; 95% CI: 3.32,6.36) were significantly associated with time of first antibiotic use. Conclusions: Earlier time of solid food introduction was associated with earlier antibiotic use. Childhood illnesses, especially ear infections, also strongly influence antibiotic initiation. These modifiable factors offer targets to reduce unnecessary early antibiotic use.

Occupational ocular injuries are a preventable yet neglected public health problem, particularly in low- and middle-income countries. Maintenance workers are exposed to diverse ocular hazards daily, yet compliance with protective measures is consistently poor. A descriptive cross-sectional study was conducted among 85 maintenance workers at the Maintenance and Essential Services Organization (MESO) of Kwame Nkrumah University of Science and Technology (KNUST), Ghana, recruited through stratified convenience sampling across seven occupational sections. A structured questionnaire assessed knowledge of ocular hazards and protective equipment, attitudes toward ocular safety, and safety practices. Data were analyzed using IBM SPSS version 26 (IBM Corp., Armonk, NY, USA); chi-square and Fishers exact tests assessed associations (p < 0.05). Participants were predominantly male (84/85, 98.8%), with a mean age of 44.5 {+/-} 10.4 years. Overall knowledge was good (mean 9.40 {+/-} 1.59 out of 11), but attitude and practice scores were average (2.78 {+/-} 0.92 and 3.27 {+/-} 0.93, respectively). Most workers correctly identified goggles and face shields as protective, but only about half recognized that ordinary sunglasses and spectacles offer inadequate protection. Although 97.6% (83/85) recognized the need for ocular protection, only 7.1% (6/85) reported consistent protective eyewear use, and fewer than half (45.9%, 39/85) had received formal ocular safety training. Routine general protective equipment use was significantly associated with ocular protection use (Fishers exact test, p = 0.011). Sand and dust particles were the leading causes of injury and only 25% (5/20) of injured workers sought formal care. Workers demonstrated good knowledge but poor attitudes and practices toward ocular safety, suggesting that knowledge alone does not translate into protective behaviour even within a relatively well-resourced institutional setting. Findings suggest that limited access to task-appropriate protective eyewear may represent an important institutional barrier. Institutional PPE supply and section-specific safety training are essential to bridge this knowledge-practice gap.

Background: Vancomycin-resistant Enterococcus (VRE) species are common healthcare-associated pathogens that cause difficult-to-treat infections. Whole genome sequencing of patients has revealed a substantial burden of patient-to-patient VRE transmission in hospitals, with patients in intensive care units (ICUs) at particularly high risk of acquisition. However, few studies adequately characterize the pathways of VRE transmission between patients in acute care settings, a necessary step to identify current gaps in infection prevention practices. By harnessing genomic clustering analyses of whole genome sequences of VRE isolates from patients, environmental surfaces, and healthcare providers (HCP) in ICUs, we aim to reconstruct indirect pathways of pathogen movement to identify patterns of VRE spread and opportunities for transmission prevention. Methods and Findings: We collected daily samples (N = 6848) from ICUs in two hospitals over 13 weeks from four main sampling sources: patients, HCP hands, patient rooms, and shared surfaces. Samples were cultured on selective media and sent for whole genome sequencing (WGS). We used genomic thresholds to identify clusters of related VRE isolates and distinguish unrelated isolates. VRE was detected in samples from 20 out of 322 unique occupant-stays (6.22%). VRE isolates were detected from all sampling sources except for shared surfaces. A total of 44 unique VRE isolates were identified, 43 Enterococcus faecium (VREfm) and one Enterococcus faecalis (VREf). Two distinct patterns of VREfm spread were observed: 1) an outbreak setting with observed patient-to-patient transmission and low VRE diversity, and 2) high VRE diversity and pathogen movement between occupant-stays facilitated by persistent HCP and environmental contamination, but no observed transmission events. VRE detection probabilities were not significantly different between occupant-stays in outbreak and non-outbreak settings (OR = 0.63, 95% CI (0.23, 1.83), p = 0.32). However, inclusion of VRE isolated from non-patient samples increased the number of occupant-stays with VRE detection from 6 to 20, a 3.3-fold increase, as compared to patient samples alone. Inclusion of non-patient samples also increased the number of VRE multi-isolate genomic clusters detected by 7-fold. Our findings are limited because sampling was primarily conducted in ICUs. Due to the combination of short ICU stay durations and imperfect test sensitivity, VRE transmission events were probably underdetected. Conclusions: Our findings characterize the complex nature of VRE transmission pathways in ICU settings. Even without an ongoing outbreak, we found substantial evidence of VRE movement between occupant-stays, facilitated by a combination of HCP hands and environmental surfaces. This study highlights the importance of environmental sampling for understanding VRE transmission potential, which is likely to be underestimated using patient sampling alone. We recommend that future studies incorporate follow-up sampling after discharge to better understand the true burden of transmission.

Background Rising antimicrobial resistance (AMR) in the African region contributes to high morbidity and mortality. Continuous national AMR surveillance is critical in understanding the spread of AMR and informing policies on containment. We present results of national AMR surveillance in Kenya Methods Passive surveillance was prospectively conducted in 20 sites in Kenya between 2021 and 2025. Sites included national and sub-national level tertiary public and private hospital laboratories. Non-duplicate isolates of WHO priority Gram-negative and Gram-positive pathogens were included in this analysis. Bacterial isolates were identified using either conventional identification methods, Analytical Profile Index or automated systems while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method or automated systems and interpreted using the Clinical and Laboratory Standards Institute guidelines. The primary outcomes were the proportions of various priority bacteria isolated and the proportions resistant to commonly used antibiotics. Results Between 2021 and 2025, there were 15,124 priority pathogens isolated with 7,592 (50.2%) from urine, 5,430 (35.9%) from blood (35.9%), and 1,784 (11.8%) from respiratory specimens. Escherichia coli and Klebsiella pneumoniae accounted for 76.3% of the priority pathogens. Resistance to 3rd generation cephalosporins was 63.2% for Escherichia coli and 79.1% for Klebsiella pneumoniae for the period 2021 to 2025 while carbapenem-resistance was 30.4% for Klebsiella pneumoniae and 7.2% for Escherichia coli. Resistance to carbapenems by Klebsiella pneumoniae increased from 17.9% in 2021 to 35.9% in 2025 while Methicillin resistance in Staphylococcus aureus increased from 36.5% in 2021 to 56.4% in 2025. Conclusion Resistance to critical antibiotics is a significant problem in Kenya, with alarming rates of Methicillin Resistant Staphylococcus aureus and carbapenem resistant Klebsiella pneumoniae. Ugent and sustained infection prevention and control measures and appropriate antimicrobial stewardship activities should be instituted across all health facilities in the country. There is need for improved access to antibiotics with activity against these resistant pathogens.

Objectives: To determine whether methicillin-resistant Staphylococcus aureus (MRSA) recov-ered from wastewater, as a proxy for community carriage, and clinical settings represent distinct populations and whether their comparison provides insight into distinctions between healthcare-associated (HA-) and community-associated (CA-) MRSA. Methods: We analyzed whole-genome sequences from 115 MRSA isolates collected in Switzer-land between 2021 and 2024, including 89 from three hospitals and 26 from six wastewater treatment plants serving the hospital catchment areas. We compared the phylogenetic relatedness, sequence types (STs), SCCmec types, spa types, antimicrobial resistance genes (ARGs), and viru-lence factors between the two sources. Results: Amongst all isolates, few were closely genetically related, with only 5% (273/6,105) of the pairwise comparisons differing by [&le;]15 core-genome single nucleotide polymorphisms. Amongst the 89 clinical isolates, there were 23 STs and 46 spa types as compared to 6 STs and 9 spa types amongst the 26 wastewater isolates. All wastewater isolates (100%, or 26/26) and most clinical isolates (64%, or 57/89) were SCCmec IV, historically associated with CA-MRSA. Pan-ton-Valentine Leukocidin genes, which historically indicated virulence associated with CA-MRSA, were detected in 37% (43/115) of isolates, including 40% (36/89) of clinical isolates and 27% (7/26) of wastewater isolates. One wastewater ST (ST97, 6/26 isolates) was phylogenetically distinct from all clinical isolates and corresponds to a known livestock-associated MRSA lineage, while other STs identified in wastewater are known to circulate in livestock or communities (ST22, ST88, ST1482). Conclusions: Our findings highlight the effectiveness of clinical surveillance in monitoring MRSA epidemiology in Switzerland, with most major lineages, antimicrobial resistance determi-nants, and virulence factors identified in wastewater also present among clinical isolates. Notably, wastewater isolates shared sequence types with known livestock and CA-MRSA lineages. This suggests wastewater supplements traditional methods in understanding community circulation but provides limited unique insight into clinical circulation.

Background: Both over- and under-antibiotic use pose major global health challenges, yet there is no consensus on how to quantify deviations from optimal prescribing or set evidence-based targets. We developed a benchmarking tool for inpatient antibiotic use and evaluated its application in 10 countries. Methods: We developed decision-tree models to estimate expected empiric antibiotic use for 11 indications, based on the WHO AWaRe book for two age groups: 28 days to 12 years and >12 years. We parameterised the models using country-specific antimicrobial resistance estimates in the 10 countries and cross-sectional Global Point Prevalence Survey (Global-PPS) case-mix data from 2021 for 10 countries and from 2015-2022 in a subset of five countries. We then compared estimated expected antibiotic use with observed empiric use (from Global-PPS) in defined daily doses for adults and days of therapy for children, across indications and AWaRe categories. Findings: In 2021, among patients aged >12 years, in all countries but one, observed empiric Access antibiotic use, as a proportion of total antibiotic use, was lower than expected and empiric Watch antibiotic use was higher than expected. Similar patterns were observed in all countries but one in patients aged 28 days to 12 years. The magnitude of discrepancies between expected and observed Access and Watch antibiotic use varied across indications and countries. The median observed-to-expected ratios of usage across countries ranged from 0.3-0.8 for Access antibiotics, and 0.7-5.3 for Watch antibiotics in patients aged >12 years in 2021. Temporal trends from repeated surveys from 2015 to 2022 showed little change in observed-to-expected ratios for Access and Watch antibiotics. Interpretation: This benchmarking tool uses Global-PPS data to quantify differences between observed antibiotic use and WHO AWaRe recommendations. Our tool can be adaptable to local guidelines, provides policy-relevant estimates of expected antibiotic use to support monitoring, procurement planning, and targeted stewardship intervention.

Work-related musculoskeletal disorders (WRMSDs) constitute the primary occupational health burden among healthcare professionals (HCPs) globally and directly threaten health workforce sustainability, a critical concern for Sustainable Development Goal 3 (Good Health and Well-being) and SDG 8 (Decent Work and Economic Growth). Despite high prevalence in Cameroon, downstream occupational effects and management strategies across hospital levels remain undocumented. A hospital-based, analytical cross-sectional study was conducted across five referral hospitals in Douala, Cameroon (2019-2022). A total of 561 HCPs were enrolled by stratified random sampling. The Modified Nordic Musculoskeletal Questionnaire and structured interviews assessed WRMSD occupational effects and management strategies. Data were analysed using IBM SPSS v26; chi-square tests and logistic regression assessed associations (p < 0.05). The 12-month WRMSD prevalence was 83.4% (468/561). WRMSDs caused absenteeism in 83.4% of affected HCPs ({chi}2 = 14.414; p < 0.001), reduced daily activity capacity in 55.6%, and job dissatisfaction in 60.4%; 38.9% were considering a career change. Management was predominantly reactive: fitness training (76.3%), rest (41.4%), and non-steroidal anti-inflammatory drugs (NSAIDs; 37.3%). Only 15.0% received physiotherapy referral, and no hospital had a formal WRMSD protocol. WRMSDs impose a substantial and measurable occupational burden on HCPs in Douala. Current management is reactive, non-standardised, and under-integrated with physiotherapy. Evidence-based, multicomponent prevention programmes, physiotherapy integration, and a national occupational health policy are urgently required to protect the healthcare workforce and advance SDG 3 and SDG 8 targets in Cameroon.

The global dissemination of antimicrobial resistance is increasingly driven by bacterial clones combining antimicrobial resistance with enhanced virulence and environmental adaptability. Escherichia coli sequence type 131 (ST131) has historically been regarded as a major disseminator of the extended-spectrum {beta}-lactamase (ESBL) blaCTX-M-15. However, the emergence of E. coli ST1193 carrying blaCTX-M-15 may represent an ongoing shift in the epidemiology of this resistance determinant. Here, we investigated the prevalence, genomic characteristics, virulence and antimicrobial resistance potential of ST1193 in comparison with ST131. A total of 1,136 E. coli isolates were recovered from touristic and non-touristic environments, hospital-associated samples, and aircraft toilets in Guadeloupe. Isolates were whole-genome sequenced and analysed for antimicrobial resistance and virulence determinants. Additionally, publicly available genomic data comprising 1,215 blaCTX-M-15-positive ST131 and ST1193 isolates were analysed to assess temporal and geographical trends. ST1193 was significantly associated with aircraft-associated samples and exhibited a higher antimicrobial resistance gene burden than ST131, while maintaining a comparable virulence factor content. Analysis of publicly available genomes revealed similar temporal emergence patterns for blaCTX-M-15-positive ST1193 and ST131, with ST1193 showing a more recent distribution and a higher number of deposited isolates in recent years, consistent with a potential ongoing clonal replacement. Comparative genomic analysis identified numerous virulence and adaptation-associated genes shared between both sequence types, while ST1193 additionally carried distinct determinants, including components of the transmissible locus of stress tolerance. Furthermore, quinolone resistance-associated mutations were strongly linked to blaCTX-M-15 carriage, particularly among ST1193 isolates. Together, these findings identify E. coli ST1193 as an emerging high-risk clone with substantial potential for blaCTX-M-15 dissemination. Its association with aircraft-associated samples further highlights the potential role of air travel in long-distance transmission and underscores the need to reconsider current surveillance strategies focused predominantly on ST131.

Background: Staphylococcus aureus is a leading cause of severe pneumonia in mechanically ventilated patients. Clinical cultures identify pathogen presence but may not reflect lower respiratory tract microbial ecology. Whether culture-confirmed S. aureus pneumonia encompasses compositional heterogeneity with prognostic implications remains unknown. Methods: We performed 16S rRNA gene sequencing and shotgun nanopore metagenomics on endotracheal aspirate samples from mechanically ventilated patients with culture-confirmed S. aureus pneumonia in a prospective ICU registry. We quantified Staphylococcus abundance, assessed correlations with culture characteristics and host inflammatory biomarkers, and examined associations with 60-day mortality using Kaplan-Meier and Cox hazards analyses. Results: Among 109 patients, semi-quantitative culture growth and methicillin resistance showed no associations with outcomes. 16S sequencing (n=54) revealed marked heterogeneity in Staphylococcus relative abundance (range 0-96.7%), with only 33% demonstrating dominance (>50%). Dominance was associated with worse 60-day survival (50% vs. 80%,p=0.013) and remained independently predictive after adjusting for age, sex, and methicillin resistance (adjusted HR 3.24 [95%CI 1.12-9.36],p=0.030). Patients with dominance exhibited elevated pentraxin-3 (p=0.01) and reduced fractalkine (p=0.02). Nanopore metagenomics (n=28) validated these findings, with high absolute S. aureus read counts independently predicting mortality (adjusted HR 11.23 [95%CI 2.25-55.9],p=0.003). In an exploratory analysis of virulence genes (n=19), staphylokinase detection was associated with the hyperinflammatory phenotype (p=0.003) and mortality (p=0.046). Conclusions: Metagenomic profiling reveals clinically meaningful heterogeneity within culture-confirmed S. aureus pneumonia, masked by conventional diagnostics. Staphylococcus dominance identifies a high-risk phenotype with elevated bacterial burden, dysregulated host responses, and increased mortality, challenging the assumption that culture positivity represents a uniform clinical entity.

Rationale. Guidelines disagree on antibacterial treatment for adults with community-acquired pneumonia and a positive respiratory viral test, particularly hospitalized patients and outpatients with comorbidities. Objectives. To estimate associations between antibacterial treatment selected for community-acquired pneumonia and outcomes in adults with virus-positive, imaging-evaluated nonsevere pneumonia. Methods. We conducted a retrospective multicenter study using Epic Cosmos data from 2016-2025. Hospitalized patients treated empirically by 24 hours were compared by continuation during hours 24-48; outpatients were compared by prescription at emergency-department discharge. Analyses were stratified by guideline-defined comorbidity and used propensity-score overlap weighting with source-cluster bootstrap confidence intervals. Exploratory analyses assessed respiratory virus, antiviral treatment, antibacterial class, and outpatient timing. Measurements and Main Results. The cohort included 376,320 adults: 275,604 inpatients and 100,716 outpatients. Inpatients who continued treatment had higher 30-day adverse-event risk without guideline comorbidity (adjusted risk difference, 1.70 percentage points; 95% confidence interval, 0.80-2.39) and with guideline comorbidity (2.56; 1.88-3.14), and longer post-landmark stay (adjusted mean ratios, 1.14 and 1.08). Exploratory class-specific analyses showed the largest adverse-event and mortality associations with broad therapy targeting resistant staphylococci or Pseudomonas; macrolide-containing and other atypical coverage showed no consistent adverse signal. Outpatient prescribing was associated with lower risks, but care-transition and residual confounding remained. Conclusions. Continued inpatient therapy after the empiric period showed no evidence of benefit and was associated with worse observed outcomes. Outpatient associations favored prescribing but remained vulnerable to care-transition and residual confounding.

Background Hospital overheating arising from more frequent heatwaves threatens healthcare staff wellbeing, patient safety and service continuity, but is often managed as an estates or seasonal problem. We examined how interacting organisational, infrastructural and experiential conditions sustain overheating vulnerability and unequal thermal burden in hospitals in the south of England. Methods We conducted a six-phase, multi-source qualitative systems inquiry integrating 129 overheating incident reports from two National Health Service (NHS) hospitals in Hampshire, England, six stakeholder interviews, two focus groups with healthcare staff and patients (n=12), and a national stakeholder refinement focus group (n=4). AI-supported thematic analysis was combined with context-mechanism-outcome synthesis and iterative AcciMap construction, to produce an integrated systems explanation. Results Twenty themes were consolidated into six interacting explanatory pathways: 1) recognition without durable resilience; 2) hidden visibility; 3) workaround-based resilience; 4) unequal adaptive capacity; 5) underuse of emergency preparedness and business-continuity systems; 6) institutional framing. The analysis indicated that, within the hospital settings investigated, overheating persisted despite recognition because ownership, information, resources and delivery capacity were fragmented across system levels. Frontline workarounds sustained care but could conceal thermal burden and defer structural adaptation. Staff and patients had unequal capacity to regulate exposure because of differences in mobility, autonomy, physiology, clinical dependency and occupational role. Existing preparedness systems offered a route from seasonal reaction to anticipatory action, but overheating was not consistently embedded within them. The AcciMap showed how shared factors connected the six pathways and identified coordinated intervention entry points across monitoring, governance, preparedness, service delivery and infrastructure. Conclusions Overheating in hospitals in England is best understood as a socio-technical patient-safety and adaptation challenge, not a single-domain estates problem. Our analysis indicates that durable resilience requires environmental intelligence linked to accountable decisions, support for staff and patient adaptation, activation of preparedness systems and long-term infrastructure change.