Journal of Hospital Infection

Background: Privacy curtains represent a uniquely difficult infection control surface because they are frequently touched by patients, visitors, and healthcare workers, yet are difficult to disinfect using routine environmental cleaning protocols. We sought to quantify the performance of a novel automated aerosolized hydrogen peroxide system against pathogens on privacy curtains. Methods: This study was performed in an enclosed office space ({approx} 65 m^3), approximating a patient exam room. Four Bacillus atrophaeus (ATCC 9372) biological indicators (BIs) were affixed to a standard polyester privacy curtain. A single one-minute fogging phase was followed by a ten-minute contact/aeration phase (total = 11 min). Four corresponding chemical indicators measured peak airborne aerosolized hydrogen peroxide concentration, and two control BIs were placed outside of the room. Results: All four BIs demonstrated complete inactivation (no growth after seven-day incubation), representing [≥] 4-log10 spore reduction. Peak dosages reached 42 ppm nearest the aerosolized hydrogen peroxide jet outlet, with the lowest value at the near point on the back side of the curtain reaching 27 ppm (exceeding the target dosage of 25 ppm). Control exposures failed to achieve sterilization. Conclusions: A next-generation aerosolized hydrogen peroxide dry-fogging disinfection system achieved full inactivation of resistant spores on both sides of privacy curtains within a short 11-minute automated cycle.

Introduction: Fighting the ventilator (FV) is characterized by a patients active counteraction of respiratory gas flow across multiple breaths during mechanical ventilation. An effective ventilation is prevented during such episodes. The objective of this exploratory study was to evaluate clinicians knowledge, perception and agreement regarding this condition. Methods: In a cross-sectional online survey, medical professionals with experience in intensive care medicine (mostly neonatal and pediatric patients) responded to 11 questions covering various clinical aspects of FV. Results: All respondents were familiar with the phenomenon and assessed it to be clinically relevant. Neonates were perceived to be predominantly affected. Promoting factors of FV included inadequate sedation and ventilation-associated factors. In clinical practice, the participants identified FV by clinical evaluation, analysis of ventilator waveforms and capnography and used both pharmacological and non-pharmacological intervention strategies. There was no consensus concerning the English terminology of the condition. Only few respondents were familiar with local guidelines to manage FV. Conclusion: Although there was consensus on the relevance of FV, diagnostics and management strategies were highly heterogeneous. Many participants agreed that poor patient-ventilator synchrony was an important cause of FV. Future work should focus on characterizing and generating evidence on FV.

Background: Indwelling urinary catheters can cause pain, urethral irritation and trauma and provide surfaces for microbial colonisation and biofilm formation. The LubriShield(R) Foley catheter incorporates a covalently bonded, superhydrophilic antifouling hydrogel designed to reduce surface friction and limit biofilm accumulation without releasing an antimicrobial agent. This study evaluated its safety and clinical performance compared with an uncoated silicone Foley catheter, including usability and patient comfort, and explored catheter-associated microbial colonisation and biofilm formation. Methods: This prospective, randomised, single-blind, single-centre controlled clinical investigation enrolled 33 adults requiring indwelling urinary catheterisation for 72 hours to 14 days. Participants received either the LubriShield(R) Foley catheter (n = 16) or an uncoated Sterimed all-silicone Foley catheter (n = 17). The primary endpoint was safety based on adverse-event reporting; the prespecified safety criterion was the absence of a serious adverse device effect in the LubriShield(R) group. Secondary endpoints included investigator-rated ease and functionality of catheter insertion and removal and participant-reported pain and irritation/discomfort assessed using 0-10 numerical rating scales. Urine microbiology, catheter colonisation and catheter-level biofilm measurements were exploratory endpoints. Analyses were performed in the as-treated population. Numerical rating scale outcomes were compared using two-sided Mann-Whitney U tests; exploratory biofilm analyses used permutation tests with bootstrap confidence intervals. Results: No serious adverse events or serious adverse device effects occurred. Nine non-serious adverse events were reported and resolved completely. At least one adverse event occurred in 4/16 (25.0%) participants in the LubriShield(R) group and 4/17 (23.5%) participants in the control group. The prespecified safety criterion, defined as the absence of a SADE in the LubriShield(R) group, was met. LubriShield(R) was rated more favourably for ease of insertion (p = 0.0096), functionality during insertion (p = 0.0051), ease of removal (p = 0.0037) and functionality during removal (p = 0.0085). Participants reported significantly less pain and irritation/discomfort during insertion, while the catheter was indwelling and during removal (all p < 0.05). Outcomes 7 {+/-} 1 days after catheter removal were similar between groups. Absolute biofilm biomass and bacterial and fungal loads did not differ significantly. In a post hoc exploratory normalised analysis, the biofilm-to-bacterial-load ratio was lower with LubriShield(R) (median 0.052 vs 0.080; permutation p = 0.043), although the bootstrap 95% confidence interval for the between-group difference included zero. Conclusions: The LubriShield(R) Foley catheter demonstrated a favourable short-term safety profile and was associated with improved investigator-rated usability and participant-reported comfort compared with an uncoated silicone Foley catheter. A post hoc exploratory analysis was compatible with reduced biofilm accumulation relative to bacterial load, but this finding is hypothesis-generating only and requires confirmation in larger, adequately powered studies with prespecified biofilm endpoints.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is one the most common cause of post-surgical infections in Malawi and poses a significant public health challenge due to resistance to commonly used antibiotics. We isolated and evaluated the stability and lytic activity of a MRSA-specific bacteriophage (Staphylophage) from Mzuzu Central hospital (MZCH) sewage against MRSA strains isolated from surgical wards. MethodsA prospective in vitro experimental study was conducted using 56 pus swabs collected from post-surgical patients at Mzuzu Central Hospital (MZCH), Malawi. Standard microbiological methods and VITEK analysis were used for bacterial isolation, identification and antimicrobial susceptibility testing of Staphylococcus aureus and MRSA according to the 2024 EUCAST guidelines. A lytic Staphylophage was isolated and purified from sewage wastewater using filtration, enrichment, and double-layer agar techniques. The purified Staphylophage was evaluated for its lytic activity through host range testing and stability under ultraviolet (UV) exposure (up to 60 minutes), different pH levels (2-12), and temperatures (4{degrees}C, -20{degrees}C, and -80{degrees}C). ResultsOut of 56 bacterial isolates, 18 (32.1%) were S. aureus, of which 11 (61.1%) were MRSA. The isolated Staphylophage showed lytic activity against 87% of Staphylococcus species tested. The phage remained stable at temperatures between -80{degrees}C and 4{degrees}C and across a pH range of 2- 12. It also retained viability after UV exposure for up to 15 minutes, although a reduction in phage titre was observed after 30 minutes. ConclusionsA lytic Staphylophage isolated from hospital sewage at MZCH demonstrated activity against Staphylococcus species, including MRSA strains from post-surgical wound infections. These findings illustrate the feasibility of generating candidate phages for alternative therapeutic approaches in a central hospital setting in Malawi.

Lines, drains, and airway devices are commonly used in surgical and inpatient care to support treatment and patient monitoring. While these devices are essential, prolonged device retention is associated with complications such as infection, tissue injury, thrombosis, and extended hospital stay. Understanding how long devices remain in place and how duration varies across device types is important for improving patient safety and guiding device management practices. This study analyzes device duration patterns using Patient Lines, Drains, and Airways (LDA) data containing information on device type, placement time, and removal time across multiple patient encounters. Exploratory data analysis and machine learning approaches are used to examine duration distributions, distinguish short and prolonged device retention, and identify structural patterns across device categories. The findings indicate notable variation in device duration patterns across categories, with identifiable differences in device retention behavior across device groups. This study highlights the value of observational electronic health record data for characterizing device exposure patterns and provides a foundation for future data-driven device management and risk assessment.

Sepsis is a substantial contributor to neonatal mortality in Africa, with Klebsiella pneumoniae as the leading causative pathogen. Incorporating molecular tools such as whole genome sequencing (WGS) into routine surveillance of important bacterial pathogens, including those causing neonatal sepsis, can support targeted deployment of infection prevention and control measures and treatment interventions. This study aimed to understand the current practices and capacity for culture, identification and genomic analysis of bacterial pathogens in Africa, with a particular focus on K. pneumoniae, to support standardised genomic surveillance. A cross-sectional online survey was distributed to various clinician and scientist networks across Africa. All respondents completed a demographics section, while sections on laboratory test capacity, blood culture practices, WGS, and bioinformatics analysis were completed based on experience in these aspects. Responses were received from 52 institutions in 25 African countries. Among 51 institutions completing the laboratory test capacity section, 61% reported performing blood cultures, with the majority using manual commercial biochemical systems for species identification (71%) and manual disk diffusion for antibiotic susceptibility testing (82%). Participating institutions reported near-universal access to a -80{degrees}C freezer, centrifuge and thermocycler, but shaking incubators were less commonly available (67%). More than half of respondents (54%) indicated that they perform the entire WGS workflow (including DNA extraction, library preparation and WGS) internally, with most performing DNA extraction internally (88%) using column-based kits (70%). Outsourcing was progressively more common at later workflow stages. Infrastructure challenges that limit bioinformatics analysis capabilities were reported by all 23 respondents who completed this question, including limited access to high-performance computing and data storage space. This survey found sufficient capacity to support genomic surveillance of neonatal sepsis pathogens across participating African institutions. However, investments in blood culture, supply chains, sequencing, bioinformatics, and data dissemination capacity are needed to realise its full potential. These findings will support the development of standardised genomic surveillance protocols tailored to the diverse capacities of African laboratories.

Background Neonatal sepsis remains a major cause of neonatal morbidity and mortality, particularly in low- and middle-income countries. Its management is increasingly complicated by antimicrobial resistance (AMR), while limited facility-specific data on causative bacterial pathogens and susceptibility patterns often necessitate empirical antibiotic treatment. This study assessed the prevalence of neonatal sepsis, bacterial pathogens and antimicrobial resistance patterns, and maternal, neonatal and clinical factors associated with neonatal sepsis among neonates admitted to the Neonatal Intensive Care Unit (NICU) at Livingstone University Teaching Hospital (LUTH), Zambia. Methods A retrospective cross-sectional record review was conducted among neonates admitted to the NICU at LUTH from 2020 to 2025. A total of 150 neonatal records were analysed. Neonatal, maternal, clinical, blood culture and antimicrobial susceptibility data were analysed using descriptive statistics, chi-square tests and logistic regression. Missing information was treated as missing and was not imputed; denominators were reported according to the records available for each analysis. Results Neonatal sepsis was identified in 52/150 neonates, giving a prevalence of 34.7% (95% CI: 27.5%-42.6%). Among the 52 sepsis cases, 20 had positive blood cultures, corresponding to a culture positivity rate of 38.5% (95% CI: 26.5%-52.0%); this represented 13.3% of the full study sample. Maternal fever during labour (aOR=6.822; 95% CI: 2.032-22.905; p=0.002) and caesarean delivery (aOR=2.245; 95% CI: 1.050-4.801; p=0.037) were independently associated with neonatal sepsis, while increasing birth weight was protective (aOR=0.891 per 100 g; 95% CI: 0.817-0.973; p=0.010). Escherichia coli was the most frequent isolate (5/20; 25.0%), followed by Klebsiella pneumoniae (4/20; 20.0%) and Staphylococcus aureus (4/20; 20.0%). Resistance was highest to ampicillin (15/19; 78.9%), followed by gentamicin and ceftriaxone (10/19; 52.6% each), while all 19 isolates tested against meropenem were susceptible. Conclusion The findings indicate that empirical management of neonatal sepsis at LUTH should be informed by local microbiological surveillance rather than reliance on historical first-line susceptibility assumptions. Routine blood culture and susceptibility testing, a regularly updated facility antibiogram, strengthened infection prevention and antimicrobial stewardship are required to improve treatment decisions and preserve effective antibiotics. Interpretation should consider the retrospective single-centre design, incomplete routine records and the small number of culture-positive isolates.

Background Temperature instability during neonatal transport contributes to adverse outcomes in preterm and low birth weight infants. Hypothermia in this population is associated with increased risk of intraventricular haemorrhage (IVH), sepsis, and death. Current transport temperature management is reactive and manually controlled. The Heating On Transport WitH prEtErm and Low birth weight neonates using Servocontrol patient temperature management system (HOTWHEELS) trial aims to determine whether automated, servo-controlled thermoregulation provides superior thermal stability compared to standard care and reduces hypothermia-associated adverse outcomes. Methods This prospective, randomised, superiority trial is conducted by the Newborn Emergency Transport Service of Western Australia. Infants with a gestational age of less than or equal to 34 weeks and/or weight of 1500 g requiring transport are randomised to serve-controlled or standard thermal care. The primary outcome is the proportion of infants with a temperature between 36.5 and 37.5 degrees Celsius on arrival at the receiving neonatal unit. Secondary outcomes include the incidence of IVH in the first 7 days, mortality before discharge, the incidence of moderate (<36.0) and severe (<35.0) hypothermia for greater than 15 minutes and the temperature change during transport. Trial registration: ANZCTR12624000503527. Impact HOTWHEELS is the first randomised trial in neonatal transport to evaluate servo-controlled temperature control. We believe the findings will inform standards of temperature control during transport for preterm and low birth weight infants.

Introduction Reliable, well-maintained laboratory equipment is essential for timely, accurate and reliable laboratory results for patient care, surveillance, and health system resilience. Tanzania implemented the Standard Medical Laboratory Equipment Guideline (SMLEG-2018) to harmonise procurement and improve efficiency across a tiered laboratory system and network. However, equipment functionality gaps remain a critical challenge for healthcare delivery. This study determined the functionality status of standardised laboratory analysers in Tanzania mainland and identified the drivers of non-functionality. Methods We conducted a facility-based cross-sectional study to identify the causes of non-functionality of standardised chemistry, haematology, and urine analysers across mainland Tanzania. We assessed 3,044 analysers and used Pareto analysis to identify the primary drivers of non-functionality. Results Of the 3,044 standardised analysers assessed, 987 (32.4%) chemistry 1,308 (43.0%) haematology, and 749 (24.6%) urine) assessed; 397 (13.0%) were non-functional. Proportionally, urine analysers were the most non-functional (n=176/749, 23.5%), followed by chemistry (n=135/987, 13.7%), and haematology (n=86/1308, 6.6%) analysers, p<0.001. Urine analysers had significantly higher non-functional equipment (23.5%), followed by Chemistry analysers (13.7%), than Haematology analysers (6.6%), p<0.001. Equipment breakdown was the leading cause of non-functionality, accounting for 70.9% (61/86), 70.5% (124/176) and 60.0% (81/135) of the non-functional haematology, urine and chemistry analysers, respectively, among all causes identified for each analyser type. Conclusion Although the SMLEG 2018 implementation identified broad coverage of functional standardised laboratory equipment, persistent equipment breakdowns of more than 10% highlight a systemic, concerning gap that requires immediate corrective action to sustain high performance. Strengthening preventive maintenance, timely repair services and sustainable equipment lifecycle planning is critical to sustaining quality laboratory services for robust preventive and curative care.

In 2024, Chicago experienced a measles virus outbreak. Air samples collected as part of routine respiratory virus surveillance from three hospitals that received measles patients were retrospectively analyzed. Measles virus was detected in air samples from one emergency department across five weeks when measles patients were present and another when no known cases were present. Two of three viral sequences derived from air samples were identical to measles patients. The source of one diverging sequence could not be identified and may represent a case not identified by traditional surveillance methods. Air sampling may supplement measles investigation, surveillance and response.

BackgroundSevere community-acquired pneumonia (CAP) remains a leading cause of mortality in children under five. The PediCAP trial evaluated oral step-down therapy using dispersible amoxicillin or amoxicillin/clavulanate tablets in African children hospitalised with severe CAP. Dispersible tablet formulations are preferred in children; however, pharmacokinetic data for oral amoxicillin/clavulanate in paediatric populations remain limited. We characterised the pharmacokinetics of 4:1, 7:1, and 14:1 dispersible amoxicillin/clavulanate tablets in children enrolled in the PediCAP trial and predicted target attainment under different dosing schemes. MethodsChildren were randomised within 24 hours of starting intravenous antibiotics to oral step-down therapy with weight-banded dosing of twice-daily amoxicillin/clavulanate (4:1, 7:1, or 14:1). Plasma concentrations were quantified following intensive sampling and analysed using nonlinear mixed-effects modelling with allometric scaling and postmenstrual age-dependent clearance maturation. Pharmacodynamic indices included %fT>MIC for amoxicillin and %fT>Ct for clavulanate. ResultsA total of 157 children (median [range] age, 12 [2-70] months; weight, 8.4 [4.0-22.0] kg) contributed 707 paired concentrations. Amoxicillin was described by a two-compartment model and clavulanate by a one-compartment model, both with sequential zero-and first-order absorption. Typical clearance for an 8-kg individual at full maturation was 11.8L/h for amoxicillin and 6.1L/h for clavulanate. Pharmacokinetics were similar between the formulation ratios. Weight-banded dosing achieved balanced exposures across weight groups. Amoxicillin achieved 40%fT>MIC for MICs[&le;]2mg/L. A proposed clavulanate target of 20%fT>0.5mg/L was achieved in most children even at the lowest amoxicillin/clavulanate ratio. ConclusionWeight-banded dosing using dispersible amoxicillin/clavulanate tablets provide consistent exposure profiles in African children with severe CAP. SUMMARYPopulation pharmacokinetic modelling of dispersible amoxicillin/clavulanate tablets (4:1, 7:1, 14:1) in 157 African children with severe pneumonia showed weight-banded dosing achieved consistent and adequate amoxicillin and clavulanate exposures across formulations.

Background: Shotgun metagenomic pipelines routinely discard host-derived reads, which can exceed 90% of reads in low-biomass clinical samples. Whether these reads support mitochondrial heteroplasmy detection, and at what allele fraction, has not been established. Methods: Shotgun metagenomic data from 47 upper respiratory tract swabs from healthy adults in Nagpur, India, were analysed. Human Reads were recruited against the rCRS and realigned competitively to GRCh38 to remove nuclear mitochondrial segments (NUMTs). Kraken2 was used as a microbial control. Heteroplasmy was called against a pooled, substitution-specific beta-binomial error model and a leave-one-out panel of normals. The detection limit was evaluated from the substitution spectrum against gnomAD v3.1. Results: Complete mitochondrial genomes were recovered from all samples (mean depth 433X, range 9-3,029X). Competitive realignment relocated 3.22% of recruited reads to nuclear loci; microbial cross-mapping removed 0.045%. Error rates varied 12.8-fold across substitution classes, with T>A being the highest. The 134 calls had a Ti/Tv of 0.43, compared with 3.51 in gnomAD, and T>A accounted for 42.5% of calls. T>A allele fractions never exceeded 4.72%, whereas transitions reached 90.81%. At a 5% threshold, T>A calls disappeared, and Ti/Tv rose to 2.20 before plateauing; 16 calls exceeded this limit. Macrohaplogroups were assigned in 46 of 47 samples (M 22, R 23, N 1). Conclusions: Metagenomic host reads support complete mitochondrial recovery, haplogroup typing, and heteroplasmy detection for allele fractions > 5%. Below this, a T>A-dominated error process persists after NUMT removal that background-fitted models do not capture.

Importance: Clinicians often look for a dental source in Staphylococcus aureus bacteremia (SAB), but how often dental disease is found, compared with other bacteremias, is unclear. Objective: To compare documented dental disease in adults with SAB, Escherichia coli bacteremia, and a general population cohort. Design, Setting, and Participants: Retrospective cohort study in the Protege database of 48 975 adults with bacteremia from January 1, 2015, through December 31, 2023, assigned by earliest in-window organism, and 81 945 general population adults. Exposures: SAB, with E coli bacteremia as the primary comparator and the general population as the secondary comparator. Main Outcomes and Measures: Documented dental disease from 7 days before through 30 days after index, defined by a qualifying dental procedure or disease-specific note text and adjusted for age, sex, race, and documentation intensity. Results: Dental disease occurred in 528 of 16 435 patients with SAB (3.21%) and 179 of 24 942 patients with E coli bacteremia (0.72%). The adjusted odds ratio was 3.86 (95% CI, 3.23 to 4.63). By the pathology-only definition, disease occurred in 517 patients with SAB (3.15%) and 399 general population patients (0.49%). The adjusted odds ratio was 3.71 (95% CI, 3.08 to 4.46). Within SAB, rates were highest with prior infective endocarditis (9.8%), opioid use disorder (6.2%), injection drug use (5.3%), and prosthetic valve (5.0%). Prevalence ranged from 0.49% in the general population to 7.98% in other streptococcal bacteremia. Of 437 patients with SAB and an assignable first finding date, 333 (76.2%) had the finding after the index date. Conclusions and Relevance: Dental disease was documented more often in SAB than in E coli bacteremia after adjustment. Most findings were first recorded after bacteremia was recognized, during SAB evaluation. These data do not show that dental disease caused the bacteremia.

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 [&le;]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.

Background. Many Indian special newborn care units (SNCUs) cannot offer amplitude-integrated EEG (aEEG) or early MRI, so bedside judgement decides which newborns receive closer neurological attention. Earlier work found that asphyxiated newborns cry with a higher pitch and shorter phonation than healthy newborns, and a meta-analysis reported higher fundamental frequency, dysphonation and atypical melody in infants with neurological dysfunction, with wide differences between studies. Aim. To determine whether basic acoustic features of a smartphone-recorded pain cry (following a heel prick) can differentiate term newborns with HIE from control newborns. Also, to track changes in cry acoustics over the first 72 hours of life and evaluate their association with the clinical severity and short-term outcomes of encephalopathy. Design. A prospective, single centre diagnostic accuracy and cohort study in a tertiary SNCU. Three groups of term newborns are recorded: newborns with HIE, healthy comparators, and sick comparators who do not have HIE. Every newborn is recorded after the same stimulus, the first clinically indicated heel-prick. Newborns with HIE and sick comparators are recorded again at 24 hours, 72 hours and before discharge. A cry that is late or absent counts as a result and not as a missing value. Three clinicians blinded to group also classify the cries by listening, so the phone-based measures can be compared with the human ear. Analysis. The primary outcome is the area under the ROC curve of a logistic model with five pre-specified acoustic predictors. The target is 180 analyzable newborns (70 with HIE and 110 comparators). Reporting follows STARD and TRIPOD+AI. Relevance. In a South Asian trial, cooling did not reduce death or disability at 18 months and increased death alone. A cry tool in this setting is therefore proposed to help prioritize EEG, seizure surveillance, closer observation and referral. It is not proposed as a trigger for cooling. Keywords: neonatal encephalopathy; infant cry; acoustic analysis; smartphone; diagnostic accuracy; low-resource setting.

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.

BackgroundFospropofol disodium is a water-soluble prodrug of propofol that avoids a lipid emulsion carrier. It may therefore reduce injection pain, cardiorespiratory depression and lipid exposure. In May 2021 it was approved in China (H20210017) for induction of general anaesthesia in adults. Randomised trials have since tested it for sedation outside the operating room, but this setting has not been systematically reviewed. MethodsWe followed PRISMA 2020 and PRISMA-S and searched Europe PMC, PubMed, Embase, Cochrane CENTRAL, Web of Science and the Chinese databases CNKI, Wanfang and VIP (the last accessed through the XJMU Library database proxy) from inception to 2026. Eligible patients were adults receiving sedation for purposes other than general anaesthesia induction or maintenance, including continuous sedation during ICU mechanical ventilation and procedural sedation. These uses are referred to here as sedation outside the operating room. We included randomised controlled trials with propofol as the comparator and excluded trials of general anaesthesia induction or maintenance to avoid overlap with the published induction meta-analysis. Binary outcomes were pooled with a DerSimonian-Laird random-effects model, and REML plus modified Hartung-Knapp estimates were reported alongside to improve interval coverage when few studies were available. Outcomes with a high proportion of zero cells were also analysed with the Peto method. We stratified by setting and blinding and performed leave-one-out analysis, trial sequential analysis (TSA) and GRADE assessment. Hypotension reached the prespecified threshold of at least 10 studies, so publication bias was assessed with the Harbord test, with the originally specified Eggers test reported alongside. The protocol was prospectively registered and took effect on 16 September 2026. All searches were completed on 21 September 2026, and screening, extraction and analysis were performed after registration. ResultsTwelve randomised controlled trials were included. Event counts for all 12 studies were checked against the full-text original publications. For Liu 2026, a preprint, counts were taken directly from its Tables 2 and 3. Compared with propofol, fospropofol disodium reduced injection pain under the DerSimonian-Laird model (8 studies, OR 0.09, 0.03-0.21) and increased pruritus/paraesthesia (4 studies, OR 32.56, 12.89-82.26; RD +28.5%). During procedural sedation, it was associated with fewer respiratory adverse events (5 studies, OR 0.19, 0.11-0.32). This composite includes respiratory depression, hypoxaemia and related events reported by individual trials and should not be extrapolated to all adult sedation settings. For hypertriglyceridaemia, the DerSimonian-Laird estimate was OR 0.29 (0.13-0.65), but all four studies were conducted in ICU settings and the REML plus modified Hartung-Knapp estimate was 0.29 (0.08-1.08), with a confidence interval crossing 1. Certainty was very low, so this finding remains hypothesisgenerating. Hypotension differed by setting: OR 0.24 (0.13-0.42) for procedural sedation and 0.90 (0.53-1.55) for continuous ICU sedation, with a significant interaction (P < 0.001). The overall estimate (OR 0.51, 0.28-0.93) is reported for summary only. Under REML plus modified HartungKnapp it was 0.51 (0.25-1.03), crossing 1, so it does not support a claim that the drug lowers blood pressure and should not be extrapolated to the ICU. Bradycardia did not differ significantly (9 studies, OR 0.45, 0.17-1.18), and the direction reversed in the only double-blind study. Two studies reported slower onset or loss of consciousness with fospropofol disodium (MD +2.22 and +0.92 min), but these were not pooled because heterogeneity was extreme (I2 = 99.6%). Recovery, discharge and successful extubation showed no clear differences, although heterogeneity was high (I2 = 85%-92%) and the evidence cannot establish equivalence. Sedation efficacy was not pooled because definitions differed. Patient-important outcomes (death, delirium, ICU length of stay and duration of mechanical ventilation) were each reported by only one or two small studies with inconsistent definitions and time points, so no reliable conclusion can be drawn. Setting-specific results should take priority over the overall mean. Certainty ranged from very low to moderate. O_TBL View this table: org.highwire.dtl.DTLVardef@174a615org.highwire.dtl.DTLVardef@143c610org.highwire.dtl.DTLVardef@807653org.highwire.dtl.DTLVardef@1d857eborg.highwire.dtl.DTLVardef@740a59_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 2:C_FLOATNO O_TABLECAPTIONBinary event counts by study and outcome (fospropofol disodium versus propofol). C_TABLECAPTION C_TBL O_TBL View this table: org.highwire.dtl.DTLVardef@538773org.highwire.dtl.DTLVardef@1e1ccbcorg.highwire.dtl.DTLVardef@1486540org.highwire.dtl.DTLVardef@1ef63f9org.highwire.dtl.DTLVardef@18ca7cb_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 3:C_FLOATNO O_TABLECAPTIONThreshold, recording window and intervention requirement for hypotension in each study (10 studies). C_TABLECAPTION C_TBL ConclusionsDuring procedural sedation, fospropofol disodium may reduce injection pain and respiratory adverse events and may lower the risk of hypotension compared with propofol. This hypotension benefit should not be extrapolated to the ICU. During continuous ICU sedation no data were available for injection pain or respiratory adverse events, so the safety evidence in that setting remains limited. Hypertriglyceridaemia was lower only under the DerSimonian-Laird model. Because the result depends on the method and certainty is very low, it cannot be treated as definitive. The main cost is a clear increase in pruritus and abnormal sensations. Onset may be slower, but the evidence comes from two bolus-dosing studies in procedural sedation, and no such disadvantage was seen during continuous ICU infusion. Evidence on sedation efficacy, recovery time, discharge time and successful extubation is limited, and equivalence between the two drugs cannot be asserted. Because most studies were small and open-label and certainty ranged from very low to moderate, these findings support investigational use only and do not justify a routine clinical recommendation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Europe PMC, PubMed, Embase, Cochrane CENTRAL, Web of Science Core Collection and Chinese databases (CNKI, Wanfang, VIP) by crossing drug terms (fospropofol, fospropofol disodium, Lusedra, Aquavan) with sedation setting terms (ICU, mechanical ventilation, endoscopy, gastroscopy, hysteroscopy, bronchoscopy, procedural sedation). Within the retrieved literature, the only relevant meta-analysis addressed general anaesthesia induction; no synthesis of the sedation setting was identified. Added value of this studyThe present synthesis focuses on sedation outside the operating room, includes 12 RCTs, and stratifies by setting. It reports eight safety and efficacy outcomes (recovery time and other continuous outcomes are reported narratively), together with heterogeneity, leave-one-out sensitivity analysis, trial sequential analysis and GRADE certainty, and it quantifies the costs of fospropofol disodium (pruritus/paraesthesia; slower onset after bolus dosing). Clinical implicationsFospropofol disodium may reduce injection pain during sedation. For hypertriglyceridaemia the result depends on the estimator and certainty is very low. During procedural sedation it may reduce hypotension and respiratory adverse events, whereas the evidence for a hypotension benefit during continuous ICU sedation is weak. Because the approved indication in China is adult general anaesthesia induction only, these uses remain investigational; they do not constitute a routine clinical recommendation. Applicability to specific patient groups remains an inference from pharmacological mechanism.

Morganella morganii is an opportunistic pathogen with intrinsic and acquired antimicrobial resistance, but its genomic epidemiology remains poorly characterized in Bangladesh. We sequenced and compared genomes of 47 stool-derived M. morganii isolates from hospital (n = 29) and community (n = 18) participants in urban Dhaka. Susceptibility testing showed frequent resistance to imipenem (70.2%) and cefuroxime (97.9%), while all isolates were resistant to colistin. Resistance to meropenem (6.4%) and ertapenem (2.1%) was uncommon. Based on acquired non-susceptibility across tested antimicrobial categories, 18/47 (38.3%) isolates were multidrug-resistant, including 15/29 (51.7%) hospital-derived and 3/18 (16.7%) community-derived isolates. Genomic analysis identified 17 {beta}-lactamase alleles including Morganella-associated chromosomal {beta}-lactamases and acquired resistance determinants, with blaOXA-1, blaDHA-21, blaCTX-M-15, and blaTEM-1 predominating. However, no recognized acquired carbapenemase genes were detected. Among 44 non-{beta}-lactam resistance genes, tetB was most frequent. Phylogenomic and average nucleotide identity analyses classified 31 isolates as M. morganii subsp. morganii and 16 as the subsp. intermedius lineage. Considerable population diversity was observed, with 33 distinct sequence types among the 47 isolates and no clear clustering by hospital or community origin. The subsp. intermedius isolates showed greater genomic heterogeneity than subsp. morganii, with a minimum within-group average nucleotide identity of 94.2%. Single nucleotide variant (SNV) analysis identified several closely related isolate groups, including an ST1 pair differing by 10 SNVs and collected three days apart within the same hospital, although direct transmission could not be established. Virulence-associated gene profiles differed between subspecies, with hemolysin- and toxin-associated genes predominantly detected among subsp. morganii isolates and largely absent from subsp. intermedius. Overall, these findings reveal substantial genomic diversity, a considerable burden of multidrug resistance, and subspecies-associated differences in virulence gene content among M. morganii circulating in Dhaka, while the frequent imipenem-non-susceptible but carbapenemase-negative phenotype highlights the need to investigate alternative carbapenem resistance mechanisms.

Infection following high-energy open fractures remains a major challenge. Open fractures are exposed to environmental and skin pathogens, which, along with traumatized tissue and implanted hardware, create a favorable environment for infection. 24-83% of open fractures yield positive culture results. Despite culture-positive wounds being at higher risk for infection, culture data are rarely used in clinical decision-making. Culture-positivity in open fractures is believed to indicate higher wound bioburden, but this hypothesis remains unconfirmed. This study aimed to correlate culture positivity and quantitative wound bioburden using next-generation sequencing (NGS) and to characterize patterns of bioburden and bacterial diversity amongst patients with open fracture and Fracture Related Infection. We hypothesized that higher wound bioburden would be associated with culture positivity. This secondary analysis of the METRC Bioburden Study included 78 patients with severe open tibia fractures who underwent standardized tissue sampling at definitive wound closure and at later fracture site revision surgery. DNA extracted from intraoperative tissue was analyzed via 16S rRNA gene amplicon sequencing. Quantitative bioburden metrics included bacterial read percentage and bacteria-to-human read ratio (BHR). Associations between sequencing-based bioburden, culture results, and clinical infection (CDC-defined) were evaluated using Mann-Whitney U tests, McNemars chi-squared tests, and unsupervised clustering analyses. Culture-positive samples exhibited significantly higher bacterial read percentages and higher log(BHR) values than culture-negative samples. Optimal thresholds yielded high sensitivity and specificity for both bacterial reads and BHR for predicting culture positivity. Neither baseline culture nor NGS positivity predicted later infection. However, follow-up samples from patients with established infection showed significantly higher bioburden and distinct microbiome structures. Clustering analyses identified two infection-associated microbial profiles: one with high bioburden and high diversity (polymicrobial infection) and one with low bioburden and low diversity (single-dominant pathogen). Culture positivity in open fractures correlates strongly with increased bacterial bioburden, indicating that positive cultures may primarily reflect microbial load rather than specific pathogens. Quantitative NGS-based measures, including bacterial read proportion and BHR, may offer a biologically grounded approach to assess wound contamination and may inform infection risk. Distinct bioburden-diversity patterns suggest heterogeneous infection phenotypes that may require tailored surgical and antimicrobial strategies.

Micro/nanoplastics (MNPs) are increasingly recognized as a persistent environmental contaminant of concern, yet polyisobutylene (PIB), an industrially significant polymer used as industrial sealants, adhesives, cable insulation, lubricant additives, and chewing gum bases, remains poorly studied relative to more commonly studied plastics such as polyethylene terephthalate (PET), polystyrene (PS), and polyethylene (PE). This study investigated the multisystem toxicological effects of chronic dietary exposure to PIB-MNPs in Drosophila melanogaster. PIB-MNPs (> 5 micron) were synthesized via the solvent evaporation method and characterized using scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR), confirming successful synthesis. Flies were chronically exposed to PIB-MNPs (1, 2, or 3 mg) alongside an SDS control and a water control to 50 mg of yeast over 21 days, with toxicological outcomes assessed via survival analysis, climbing assays, fluorescence brain imaging, fertility/fecundity assays, the Smurf gut-permeability assay, Ellman's AChE activity assay, and RT-qPCR analysis of Stat92E expression, a marker of inflammation. Chronic exposure to PIB-MNPs reduced survival, with females exhibiting markedly greater susceptibility than males. Exposure progressively impaired locomotor performance and induced brain vacuolization suggestive of neurodegeneration, peaking at day 15. AChE activity declined in a concentration-dependent manner by day 21. Female fecundity, egg-hatching rate, and ovarian egg-chamber maturation were significantly reduced, while male gonadal cyst cell numbers remained largely unaffected. PIB-MNPs exposure also induced a positive Smurf phenotype, indicating compromised intestinal barrier integrity and upregulated Stat92E expression, consistent with activation of a systemic stress response. Notably, several endpoints showed non-monotonic, concentration-independent trends, suggesting particle aggregation may influence effective bioavailability. Collectively, these findings establish PIB-MNPs as a multi-system toxicant in Drosophila.