OBJECTIVES:Post-intensive care syndrome (PICS) and PICS-family (PICS-F) lead to lasting physical, cognitive, and psychologic challenges among survivors of critical illness and their caregivers. It is unclear how best to support these individuals. We aimed to evaluate the feasibility of a co-designed, multicomponent post-ICU follow-up intervention and to explore its association with symptoms of PICS and PICS-F. DESIGN:This was a pragmatic, mixed-methods randomized controlled trial. SETTING:This study was conducted at an academic ICU in Canada. PATIENTS:We enrolled 20 patient-caregiver dyads (n = 40 participants). Patients were eligible if they were 18 years old or older, expected to survive greater than or equal to 6 months after discharge from ICU, and were at high-risk for PICS. Caregiver participants were adult caregivers of enrolled patients. INTERVENTIONS:Dyads were randomized 1:1 to receive usual care or an intervention bundle co-designed with patients and caregivers, consisting of an ICU diary, informational materials, and two multidisciplinary follow-up clinic visits at 1 and 3 months after ICU discharge. MEASUREMENTS AND MAIN RESULTS:Trial outcomes included feasibility metrics, qualitative interviews, process evaluation, and clinical measures at 6 months. Qualitative data were analyzed using reflexive thematic analysis. Quantitative outcomes included PICS symptomatology, quality of life, caregiver burden, healthcare utilization, and functional status. The consent rate was 87.5%, with a mean enrollment of 5.25 participants/month. Twenty dyads were randomized; one ICU participant in each group died before their 6-month follow-up. Seven of nine dyads in the intervention and all nine in the control completed 6-month follow-up. Intervention group survivors had lower depressive symptom scores compared with controls. Intervention group caregivers reported higher emotional well-being and social functioning scores and lower anxiety, depression, and caregiver burden. Qualitative findings demonstrated greater emotional support, preparedness, and continuity of care in the intervention group. CONCLUSIONS:Our post-ICU care bundle was feasible and may be associated with improved psychosocial outcomes.

ICU-acquired weakness (ICU-AW) research focuses predominantly on intrinsic muscle pathology rather than integrated systemic interactions, commonly studied in exercise science. Peak oxygen uptake (V ̇O_2peak), V ̇O_2 on/off kinetics, and skeletal muscle oxygenation provide quantitative evaluation of exercise capacity, and are infrequently measured in ICU survivors. Routine cardiopulmonary exercise test (CPET) research separates V ̇O_2peak and V ̇O_2 kinetics assessments into multiple sessions. Yet, a combined experimental approach may enhance diagnosis, follow-up retention, and mechanistic insight for patients with ICU-AW. This prospective cross-sectional observational study aims to develop a standardized, single-session CPET protocol for combined assessment of V ̇O_2peak, V ̇O_2 kinetics, and skeletal muscle microvascular oxygenation in ICU survivors, enabling quantitative and integrated assessment of ICU-AW. Adults mechanically ventilated ≥ 7 days will be recruited to participate 6 months post-ICU discharge, in a modified CPET exercise session on an upright cycle ergometer. The proposed standardization will involve (i) the estimation of V ̇O_2peak using a priori formulae with a V ̇O_2peak correction factor for the ICU population, (ii) V ̇O_2 on-kinetics (constant-work-rate [CWR]) targeting relative 30% V ̇O_2reserve, (iii) an incremental ramp exercise based on self-reported functional status, and (iv) a 10-minute recovery to quantify V ̇O_2 off-kinetics. In addition, near-infrared spectroscopy (NIRS) will be placed on the vastus lateralis muscle to simultaneously collect tissue saturation index (TSI) and deoxy-hemoglobin (HHb) during each phase of the protocol. Recruitment is anticipated to begin in June 2026, and is expected to be completed in 2028. Anticipated sample size will be approximately 25 participants based on convenience sampling and recruitment of 1 participant per month. The ICU-CARE CPET protocol will enable the quantitative evaluation of V ̇O_2peak, V ̇O_2 on/off kinetics, and local microvascular skeletal muscle oxygenation during a single exercise session, facilitating the integrated physiological study of ICU-AW. Registered at clinicaltrials.gov under the clinical study ID NCT06193980

IMPORTANCE:. Apnea testing is an integral component of brain death (BD) assessments. The optimal method of Apnea Testing is currently not known. OBJECTIVES:. To describe the current use of apnea test methods, and compare the effect of the chosen apnea test method (passive oxygenation, continuous positive airway pressure [CPAP], or exogenous Co2) on safety and duration of apnea test in adult BD/death by neurologic criteria (DNC) organ donors. DESIGN:. A prospective multicenter observational study. SETTING:. Seventy-four ICUs in Ontario, Canada, who participate in organ donation practices. PATIENTS:. All BD/DNC assessments in Ontario, Canada, from July 2023 to August 2024. INTERVENTIONS:. None. MAIN OUTCOMES AND MEASURES:. Outcomes included the rate of apnea test attempts, completions, and adverse events. We also measured the incidence of each method used and the duration of the apnea test. RESULTS:. During the 1-year study period, a total of 368 BD/DNC assessments were performed, of which 361 (98%) attempted an apnea test. Of the 361 apnea tests attempted, 236 (65%) used passive oxygenation (tracheal insufflation), 103 (29%) used CPAP-based methods, and 22 (6%) used exogenous Co2. Nine tests were not completed: seven were terminated due to adverse events (all with passive oxygenation; five hypoxemia, two hemodynamic instability) and two due to observed respiratory effort. All adverse events occurred with the passive oxygenation method (p = 0.20). No statistically significant differences were seen in apnea test duration between methods. The median test durations were 12 minutes (interquartile range [IQR], 10–17 min), 12 minutes (IQR, 8–15 min), and 15 minutes (IQR, 11–25 min) for passive oxygenation, positive pressure, and exogenous Co2, respectively. CONCLUSIONS AND RELEVANCE:. In this large multicenter study, passive oxygenation was associated with a nonsignificant increase in adverse events compared with CPAP-based and exogenous Co2 methods. Exogenous Co2 did not shorten apnea test time. These findings support further investigation of CPAP-based methods as an alternative approach to apnea testing and refinement of Co2 delivery parameters.

BACKGROUND:Central venous catheters have been historically preferred over peripheral venous catheters for the administration of vasoactive medications in critically ill patients to reduce the risk of extravasation. Peripheral vasopressor administration is gaining attention as a strategy to expedite initiation while avoiding the procedural risks of central venous catheter placement. Although prior systematic reviews have focused on anatomical site and peripheral venous catheter gauge, the impact of implementing a peripheral vasopressor protocol on the safety profile of peripheral vasopressor administration has not been systematically evaluated. OBJECTIVE:To determine whether a peripheral vasopressor protocol influences the safety profile of peripherally administered vasopressors in critically ill patients. STUDY DESIGN AND METHODS:A comprehensive search was conducted across MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials (Ovid), and PubMed, encompassing studies published since January 2000. Statistical analysis was conducted using R (v. 4.4.3; https://www.r-project.org/), with two-tailed significance set at p < 0.05. RESULTS:A total of 22 studies involving 10,983 adult patients (≥18 years) were identified. Median extravasation rates were similar between studies using a peripheral vasopressor protocol and those not (33.5 [12.3-53.0] vs. 31.2 [12.0-39.6] per 1000 patients), with no statistically significant difference (U = 68, p = 0.78). CONCLUSION:This review demonstrated that peripheral vasopressor protocols did not yield statistically significant reductions in extravasation rates among patients receiving peripheral vasopressor therapy.

Background Interventions to improve outcomes for critically ill patients are complex, thus it is crucial to study intervention implementation using a process evaluation. However, process evaluation methods are not well understood. Objective The aim of this study was to describe and evaluate a 1-day in-person interactive workshop, using five critical care studies as case examples, to build capacity for conducting process evaluations of complex interventions. Methods Instructors with process evaluation expertise developed preworkshop content. Each instructor and study principal investigator (PI) identified knowledge holders to participate in the workshop. Participants formed multidisciplinary working groups to develop process evaluation protocols for each study. We collected participant feedback on workshop structure and content immediately post workshop. Data were analysed using descriptive statistics. We contacted PIs 1-year post workshop to understand process evaluation progress. Results Preworkshop content covered four topics: (i) process evaluation methods; (ii) complex interventions; (iii) patient engagement and mixed methods; and (iv) health technology assessment. Thirty-six participants attended and rated it highly (n = 25 respondents), with relevant (median [1st, 3rd quartile]: 5 [5, 5]) and comprehensive (5 [5, 5]) content. Participants assessed the instructors as knowledgeable, prepared, and responsive (5 [5, 5]) for all three items (n = 24). All respondents would recommend the workshop to others (n = 19, 100%). At 1 year, four of five PIs advanced their process evaluations. Conclusion We delivered a 1-day workshop on designing and conducting process evaluations for critical care complex interventions. The workshop was well received, and content can be used for future process evaluation education, and the format can inform the conduct of similar initiatives.

Frailty is a state of diminished physiological reserve and heightened vulnerability to stressors. Strong observational evidence shows that frailty is common in critically ill patients and is associated with prolonged hospitalization, functional decline, and increased mortality. To address these challenges, an international, multidisciplinary group of experts in critical care, frailty, rehabilitation, outcomes, and research methodology convened to review current evidence, identify gaps, and outline a research agenda to improve the recognition, management, and outcomes of critically ill patients with frailty. The consensus was that further research is needed to identify frailty assessment tools suitable for widespread use, determine which patient populations should undergo screening, and evaluate whether frailty assessments improve clinical outcomes. Additional priorities include investigating the biological mechanisms of frailty and their interaction with critical illness, and understanding how these factors influence treatment response. The development and evaluation of frailty-informed interventions, spanning acute care through post-ICU and after hospital recovery, are essential to improving function and quality of life. Finally, there is a need to refine outcome measures and determine which outcomes matter most to older adults living with frailty. Advancing care for this population will require high-quality evidence on how frailty-informed care can support decision-making and improve outcomes.

Purpose In comatose patients at risk of death by neurologic criteria (DNC), spinal-mediated movements (SMM) and movements of unclear neuroanatomic origin (MUO) are occasionally challenging to discriminate from cerebral-mediated movements. Our objectives were to assess the respective prevalence and semiology of SMM and of MUO in this population and to estimate the associations between these movements with cerebral blood flow and perfusion.Methods In this prospective cohort study conducted in 15 intensive care units across Canada, we enrolled consecutive, brain-injured adults with an unconfounded Glasgow Coma Scale score of 3. Physicians conducted standardized DNC clinical evaluation, and participants underwent a brain CT-perfusion scan with CT-angiography reconstructions within a 2-h delay. We assessed the prevalence and semiology of SMM and MUO with descriptive statistics. We estimated the associations between SMM and MUO with cerebral blood flow and brain perfusion using generalized linear mixed models with a logit link function, age and sex as covariates, and random intercepts for study sites.Results We included 282 participants with a median [IQR] age of 60 [47-69] years. The respective prevalence of SMM and MUO were 27% (95% CI: 22-32%) and 12% (95% CI: 9-16%). SMM and MUO were not associated with the presence of cerebral blood flow on CT-angiography (aOR for SMM: 1.14, 95% CI: 0.63-2.05; aOR for MUO: 1.36, 95% CI: 0.61-3.01) or brain perfusion on CT-perfusion (aOR for SMM: 1.44, 95% CI: 0.77-2.68; aOR for MUO: 1.75, 95% CI: 0.77-3.97). Findings were similar in the subgroup of 204 patients fulfilling clinical criteria for DNC.Conclusions SMM and MUO are common among comatose patients at risk of DNC. Their prevalence is similar among alive comatose patients and patients fulfilling clinical criteria for DNC. These movements are not associated with cerebral blood flow on CT-angiography or brain perfusion on CT-perfusion.Trial registration: Registered on ClinicalTrials.gov: NCT03098511 on March 27, 2017.

OBJECTIVES:Summarize the prognostic performance of existing clinical prediction models (CPMs) for neuroprognostication after out-of-hospital cardiac arrest (OHCA). DATA SOURCES:We searched Medline and Embase databases from inception to June 1, 2025. STUDY SELECTION:We selected English-language studies that included adults with OHCA and evaluated a CPM for the prediction of poor functional outcome. We excluded derivation cohorts for prognostic scores and excluded models without at least two external validation cohorts. DATA EXTRACTION:Two authors performed citation screening and data extraction. Where possible, we pooled the sensitivity and specificity of poor functional outcome, and the area under the receiver operating characteristic curve (AUROC) values for each CPM. We assessed risk of bias using the Prediction model study Risk of Bias Assessment Tool, and rated the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. DATA SYNTHESIS:We included 39 observational cohorts (95,037 patients) evaluating 11 different CPMs, with the two most common scores being the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. An OHCA score greater than or equal to 17 had a pooled sensitivity of 81.8% (95% CI, 65.8-91.4%) and specificity of 74.2% (95% CI, 58.8-85.3%), while a score of greater than or equal to 32 had a pooled sensitivity of 64.9% (95% CI, 44.0-81.3%) and specificity of 89.5% (95% CI, 75.9-95.8%) for poor functional outcome (low certainty). A CAHP score greater than or equal to 150 had a pooled sensitivity of 81.3% (95% CI, 77.7-84.4%) and specificity of 77.0% (95% CI, 70.6-82.4%) for poor functional outcome (moderate certainty). Pooled AUROCs across the 11 CPMs varied from 0.75 to 0.88, with substantial heterogeneity. CONCLUSIONS:CPMs for neuroprognostication after OHCA demonstrate only moderate accuracy, with substantial heterogeneity across validation cohorts. These limitations restrict their clinical utility, particularly for irreversible decisions such as withdrawal of life-sustaining therapy.

ABSTRACT Introduction There is increasing interest in the peripheral administration of vasopressors for two main reasons: (1) to expedite vasopressor initiation in patients with refractory shock and (2) to avoid the potential complications associated with central venous catheter placement. The current evidence on the use of peripheral vasopressor administration is primarily based on single-center observational studies. There are inconsistencies in the administration of peripheral vasopressors, including catheter gauge and location, monitoring practices, vasopressor concentrations, and duration of use. This has made it difficult for institutions to develop best practice guidelines. A randomized controlled trial is needed to address this knowledge gap. Methods and analysis The P eripheral U se of L ow-dose Vasopressors for S afety and E fficacy (PULSE) in the intensive care unit is a prospective, unblinded feasibility study. Eligible patients will be 18 years or older, have no existing central venous catheter or peripherally inserted central catheter and have the presence of shock requiring a minimum vasopressor dose of any of the following: norepinephrine 0.0625 mcg/kg/min, phenylephrine 0.625 mcg/kg/min, and epinephrine 0.0625 mcg/kg/min. Fifty patients will be randomized 1:1 into either the peripheral venous catheter or central venous catheter group. The primary outcome is feasibility, defined as (1) a recruitment rate of 4 participants per month, (2) a data capture rate of ≥90%, and (3) a <50% conversion rate from peripheral to central access. The secondary outcomes include the safety of peripheral vasopressor use, alive and central-line-free days, the number of attempts needed to place a catheter, volume status, in-hospital mortality rate, ICU and hospital length of stay, and patient-centred important outcomes. Implications The data collected from this study will inform the design of a definitive randomized controlled trial to assess the safety and efficacy of protocol-driven peripheral vasopressor administration. Ethics and dissemination This study received approval (6042888) from the Queen’s University Health Sciences/Affiliated Teaching Hospitals Research Ethics Boards. Results of this study will be presented at critical care conferences and submitted for publication. Trial registration number NCT06920173 ( https://clinicaltrials.gov/study/NCT06920173 ).

OBJECTIVES:. Critically ill patients have a high risk for delirium, which may result from inadequate cerebral perfusion. One resuscitation goal for adult critically ill patients is maintaining mean arterial pressure (MAP) greater than 65 mm Hg, regardless of diagnosis or patient characteristics. Recent data suggest a high degree of individual variability in optimal MAP (MAPopt) due, in part, to whether autoregulation is intact or absent. The overall objective of this study was to evaluate the feasibility of maintaining critically ill patients within an individualized MAPopt range identified noninvasively with near-infrared spectroscopy, a technology that measures regional cerebral oxygen saturation (rSo2). DESIGN:. Pilot interventional feasibility study. SETTING:. Mixed ICU at a tertiary hospital. PATIENTS:. Sixteen adult critically ill patients were enrolled within 24 hours of ICU admission. Exclusion criteria included expected survival less than 24 hours, neurologic or neurosurgical diagnoses, absence of an arterial catheter, or pregnancy. INTERVENTIONS:. MAP and rSo2 data were recorded for 24 hours and processed through a custom algorithm. A running correlation coefficient between MAP and rSo2 was generated. Periods where there was zero or negative correlation between MAP and rSo2 reflected intact autoregulation. The MAP range where this correlation was near zero was determined to be the MAPopt. Vasoactive medications were used to maintain patients within that target range for the next 48 hours. MEASUREMENTS AND MAIN RESULTS:. The enrollment rate was 0.5 patients/mo (goal 1/mo). MAPopt was successfully identified in 12 patients (75%) and maintained for 61% ± 17% of the follow-up period. The proportion of time spent within MAPopt strongly correlated with the width of the MAPopt range (r = 0.729; p = 0.017). There were no adverse events associated with the intervention. CONCLUSIONS:. Although enrollment was lower than expected, MAPopt was calculated in the majority of patients. Maintaining patients within individualized MAPopt ranges was challenging, particularly when this range was narrow.

Background:Intensive care unit-acquired weakness (ICU-AW) research focuses predominantly on intrinsic muscle pathology rather than integrated systemic interactions, which are commonly studied in exercise science. Peak oxygen uptake (V˙O2peak), V˙O2 on/off kinetics, and skeletal muscle oxygenation provide a quantitative evaluation of exercise capacity and are infrequently measured in intensive care unit (ICU) survivors. Routine cardiopulmonary exercise test (CPET) research separates V˙O2peak and V˙O2 kinetics assessments into multiple sessions. Yet, a combined experimental approach may enhance diagnosis, follow-up retention, and mechanistic insight for patients with ICU-AW. Objective:This prospective cross-sectional observational study aims to develop a standardized, single-session CPET protocol for combined assessment of V˙O2peak, V˙O2 kinetics, and skeletal muscle microvascular oxygenation in ICU survivors, enabling quantitative and integrated assessment of ICU-AW. Methods:Adults mechanically ventilated for ≥7 days will be recruited to participate 6 months post-ICU discharge in a modified CPET exercise session on an upright cycle ergometer. The proposed standardization will involve (1) the estimation of V˙O2peak using a priori formulas with a V˙O2peak correction factor for the ICU population, (2) V˙O2 on-kinetics (constant work rate) targeting relative 30% V˙O2reserve, (3) an incremental ramp exercise based on self-reported functional status, and (4) a 10-minute recovery to quantify V˙O2 off-kinetics. In addition, near-infrared spectroscopy will be placed on the vastus lateralis muscle to simultaneously collect tissue saturation index and deoxyhemoglobin during each phase of the protocol. Results:Recruitment is anticipated to begin in June 2026 and is expected to be completed in 2029/2030. The anticipated sample size will be approximately 48 participants based on the feasibility of recruiting 1 participant per month and a sample size calculation based on Bland-Altman limits of agreement between predicted and measured V˙O2peak. Conclusions:The intensive care unit combined assessment of cardiorespiratory exercise (ICU-CARE) CPET protocol will enable the quantitative evaluation of V˙O2peak, V˙O2 on/off kinetics, and local microvascular skeletal muscle oxygenation during a single exercise session, facilitating the integrated physiological study of ICU-AW.

We conducted a single-center prospective cohort study in Ontario, Canada, to assess concomitant pulmonary embolism (PE) in hyperacute stroke. Stroke CT angiography was modified to start at the diaphragm in order to include the chest. Primary outcome of PE was reported by cardiothoracic/chest radiologists. 12/208 stroke patients had an acute PE (5.8%), all of which were clinically asymptomatic, despite imaging in some showing right-heart strain. None had cancer and only half had a patent foramen ovale. Patients with PE tended to have more severe stroke, large vessel occlusion and worse outcomes. The implications and management of these findings require further exploration.

In moderate-to-severe traumatic brain injury (TBI), anemia may exacerbate secondary cerebral injury, and patients with multiple trauma may be especially vulnerable to cerebral hypoxia. We conducted a secondary analysis of the HEMOTION trial (liberal transfusion strategy > 10 g/dL vs. restrictive > 7 g/dL), to assess whether multiple trauma modifies the effect of transfusion strategy after moderate-to-severe TBI. We included all HEMOTION trial participants (n = 742) and defined multiple trauma using three definitions: (1) extracranial injury with Injury Severity Score (ISS) > 15; (2) extracranial injury requiring emergency extracranial surgery; (3) spinal injury with neurological deficit. The primary outcome was the 6-month Glasgow Outcome Scale Extended (GOS-E). We tested interactions between transfusion strategy and multiple trauma status using sliding dichotomy and hierarchical Poisson regression, with sensitivity analyses using classical dichotomy (GOS-E ≤ 4) and proportional odds models. Secondary outcomes included mortality, quality of life (EQ-5D-5L, QOLIBRI), functional independence (FIM), and depression (PHQ-9). We found no interaction between multiple trauma status and transfusion strategies on the 6-month GOS-E across all three definitions. The adjusted relative risk (RR) of an unfavourable outcome with the liberal strategy was 0.87 (95

Current guidelines recommend a uniform mean arterial pressure (MAP) target for resuscitating critically ill patients; for example, 65 mmHg for patients with sepsis and post-cardiac arrest. However, since cerebral autoregulation capacity likely varies widely in patients, uniform target may be insufficient in maintaining cerebral perfusion. Personalized MAP targets, based on a non-invasive determination of cerebral autoregulation, may optimize perfusion and reduce complications. This scoping review summarizes the numerical values, feasibility, and clinical data on personalized MAP targets in critically ill patients. The focus is on non-invasive monitoring, such as near-infrared spectroscopy and transcranial doppler ultrasound, due to their safety, practicality and applicability to patients with- and without brain injury. Following PRISMA-ScR guidelines, a systematic search of Ovid MedLine, Embase (Ovid), and the Cochrane Library (Wiley) was conducted on September 28, 2023. Two independent reviewers screened titles, abstracts, and full texts for eligibility and manually reviewed references. Of 7,738 studies were identified, 49 met the inclusion criteria. Of these, 45 (92

Introduction Survivors of critical illness and their caregivers are at risk for long-term cognitive, physical and psychiatric impairments known as post-intensive care syndrome (PICS) and PICS-family, respectively. This study will assess the feasibility of a randomised controlled trial (RCT) evaluating an intensive care unit (ICU) follow-up care bundle versus standard-of-care for ICU patients and their caregivers.Methods and analysis This is a single-centre feasibility study. Survivors of critical illness will be eligible if: age ≥18 years, life expectancy ≥6 months and high risk for PICS. We define high risk as ICU stay ≥4 days or involving 1+ of mechanical ventilation, tracheostomy, delirium or lack of access to a primary care physician (PCP). 20 ICU survivor-primary caregiver dyads will be enrolled (n=10 dyads per group) and randomised 1:1 to the intervention versus control group. The intervention will be: (1) diaries to journal patient experiences, (2) information packages on expectations post-discharge and (3) specialised follow-up care at 1 and 3 months post-discharge. The control group will receive standard of care in the ICU and follow-up with their PCP. The primary outcome is feasibility, defined as: (1) consent rate >80%, (2) enrolment rate of 4 participants/month, (3) follow-up rate>70% and (4) data capture rate >80%. Our secondary objective is to explore the perspectives of survivors of critical illness and their families about the intervention and their participation in the study. Tertiary outcomes will be a battery of cognitive, physical functioning and psychiatric outcomes.Implications Survivorship from critical illness extends beyond surviving an ICU stay. This project will lay the foundation for performing a large, multicentre pragmatic RCT with survivors of critical illness and their caregivers, paving the way for improved long-term healthcare.Ethics and dissemination This study has received approval (6039808) from the Queen’s University Health Sciences/Affiliated Teaching Hospitals Research Ethics Board. Results will be presented at critical care conferences. A lay summary co-designed with ICU survivor participants will be provided to patients.Trial registration number NCT06681649.

BACKGROUND:Bacterial meningitis is a rare but severe infection that has a high risk of mortality and morbidity. The study objective was to describe the microbiology, long-term mortality risk, and complications from neurologic sequelae for bacterial meningitis. METHODS:This retrospective cohort study included adults with a positive cerebrospinal fluid (CSF) bacterial culture collected from 2014 to 2022 inclusive in Ontario, Canada. Patients were followed for 1 year. The primary outcome was all-cause mortality. Secondary outcomes included aspiration, enteral feeding tube insertion, decubitus ulcers, falls and/or fractures, and long-term care admissions. RESULTS:856(2.1%) patients had positive CSF cultures including 431(50.4%) community-acquired, 255 (29.8%) nosocomial and 170(19.9%) post-neurosurgical meningitis cases. Staphylococcus aureus was the second most common pathogen in community-acquired meningitis (10.9%) and the most common pathogen in nosocomial (11.8%) and post-neurosurgical (22.9%) meningitis. All-cause mortality at 30, 90, 180, and 365 days were 11.4%, 13.2%, 14.8% and 16.5% for community-acquired meningitis; 16.5%, 22.4%, 25.1% and 27.1% for nosocomial meningitis; and 10.6%, 20.0%, 25.9% and 28.8% for postneurosurgical meningitis. Enteral feeding tube was inserted in 2.8%, 15.3%, and 20.0% of community-acquired, nosocomial, and post-neurosurgical meningitis cases respectively. Other secondary outcomes occurred rarely. CONCLUSION:S. aureus was an important pathogen. Meningitis mortality continued to increase over 1 year. For nosocomial and post-neurosurgical meningitis, one in four died by 1 year and many required enteral feeding tube.

Background:Maintaining a diverse gut microbiome and minimizing antimicrobial resistance gene (ARG) carriage through reduced antibiotic utilization may decrease antimicrobial resistance. We compared gut microbiome disruption and ARG carriage following 7 or 14 days of antibiotics for treatment of bacteremia in a substudy of the BALANCE randomized controlled trial. Methods:The BALANCE randomized controlled trial enrolled 3631 participants with bacteremia, who were randomized 1:1 to receive 7 or 14 days of antibiotics. Rectal swabs were collected from 131 participants and analyzed with metagenomic sequencing to characterize the gut microbiome and ARGs. The primary outcome was change in gut microbiome diversity at day 7 vs 14. Results:Forty-one participants (n = 28 in the 14-day group, n = 13 in the 7-day group) had samples available for the primary analysis, with an imbalance in piperacillin-tazobactam exposure between groups. Change in gut microbiome diversity at day 7 vs 14 was comparable between the 14-day group (median, 0.07; IQR, -0.46 to +0.51) and 7-day group (median, 0.19; IQR, -0.77 to +0.22; P = .49). Change in ARG abundance at day 7 vs 14 did not differ by treatment duration, nor did the abundance of individual ARGs. We did not observe any change in gut microbiome diversity or ARG carriage at enrollment vs day 7. Conclusions:In this subset of patients from the BALANCE randomized controlled trial, we did not detect greater gut microbiome disruption or ARG carriage among participants who received 14 vs 7 days of antibiotics, but we were limited by small sample size and imbalances between groups.