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Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.

IMPORTANCE:. The interhospital transfer (IHT) of patients with sepsis to higher-capability hospitals may improve outcomes. Little is known about patient and hospital factors associated with sepsis IHT. OBJECTIVES:. We evaluated patterns of hospitalization and IHT and determined patient and hospital factors associated with the IHT of adult patients with sepsis. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. A total of 349,938 adult patients with sepsis at 329 nonfederal hospitals in California, 2018–2019. MAIN OUTCOMES AND MEASURES:. We evaluated patterns of admission and outward IHT between low sepsis-, intermediate sepsis-, and high sepsis-capability hospitals. We estimated odds of IHT using generalized estimating equations logistic regression with bootstrap stepwise variable selection. RESULTS:. Among the cohort, 223,202 (66.4%) were initially hospitalized at high-capability hospitals and 10,870 (3.1%) underwent IHT. Nearly all transfers (98.2%) from low-capability hospitals were received at higher-capability hospitals. Younger age (< 65 yr) (adjusted odds ratio [aOR] 1.54; 95% CI, 1.40–1.69) and increasing organ dysfunction (aOR 1.22; 95% CI, 1.19–1.25) were associated with higher IHT odds, as were admission to low-capability (aOR 2.79; 95% CI, 2.33–3.35) or public hospitals (aOR 1.35; 95% CI, 1.09–1.66). Female sex (aOR 0.88; 95% CI, 0.84–0.91), Medicaid insurance (aOR 0.59; 95% CI, 0.53–0.66), home to admitting hospital distance less than or equal to 10 miles (aOR 0.92; 95% CI, 0.87–0.97) and do-not-resuscitate orders (aOR 0.48; 95% CI, 0.45–0.52) were associated with lower IHT odds, as was admission to a teaching hospital (aOR 0.83; 95% CI, 0.72–0.96). CONCLUSIONS AND RELEVANCE:. Most patients with sepsis are initially hospitalized at high-capability hospitals. The IHT rate for sepsis is low and more likely to originate from low-capability and public hospitals than from high-capability and for-profit hospitals. Transferred patients with sepsis are more likely to be younger, male, sicker, with private medical insurance, and less likely to have care limitation orders. Future studies should evaluate the comparative benefits of IHT from low-capability hospitals.

Abstract Introduction Hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP) are associated with significant healthcare resource utilization (HCRU). This a priori, exploratory, secondary analysis from the ASPECT-NP clinical trial evaluated resource utilization among patients with ventilated HABP (vHABP)/VABP treated with ceftolozane/tazobactam or meropenem. Methods This analysis used data from the randomized, double-blind, noninferiority phase 3 ASPECT-NP trial of patients with vHABP/VABP randomized to receive ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) or meropenem 1 g for 8–14 days. Day 28 outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, and time to mechanical ventilation extubation in the microbiological intention-to-treat (mITT) population and in an HCRU population. The HCRU population, a subset of patients from the mITT population that were alive at day 28, was used to remove resource use bias influenced by mortality rates. Results Ceftolozane/tazobactam-treated versus meropenem-treated patients, respectively, had fewer deaths (20.1% vs. 25.5%), fewer hospital discharges (30.7% vs. 32.4%), and higher ICU discharges (60.0% vs. 58.3%) and extubations (51.9% vs. 48.2%) by day 28. In the HCRU population, adjusted LOS differences (95% confidence intervals) for ceftolozane/tazobactam compared with meropenem were 0.1 (− 1.4 to 1.6) hospitalization days, − 1.4 (− 2.9 to 0.2) ICU days, and − 0.9 (− 2.4 to 0.7) mechanical ventilation days. Patterns were similar among the VABP and Pseudomonas aeruginosa subgroups. Conclusion Similar 28-day resource utilization outcomes were observed between ceftolozane/tazobactam and meropenem in the mITT population of patients from ASPECT-NP with vHABP/VABP due to gram-negative pathogens. ASPECT-NP was not powered to detect differences in resource utilization outcomes between treatment groups; however, numerical differences in ICU LOS and duration of mechanical ventilation were noted. Further study is needed to assess resource utilization in the real-world practice setting, especially among patients excluded from ASPECT-NP, including those with resistant P. aeruginosa infections. Trial Registrations ClinicalTrials.gov: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

OBJECTIVES/GOALS: Regionalized sepsis care could improve sepsis outcomes. There are no measures of sepsis capability to guide the identification of hospitals that can best serve sepsis patients. We derived Capability-Based (CB) scores from specific hospital characteristics and evaluated their performance as system predictors of mortality among adults with sepsis. METHODS/STUDY POPULATION: We used the 2018 State Inpatient Databases to identify 90051 adult sepsis encounters at 157 non-federal NY hospitals (derivation cohort), and 130,249 sepsis encounters at 220 hospitals in FL and MA (validation cohort). We used Principal Component Analysis to analyze to reduce 14 hospital-level resource use characteristics to 3 interpretable, linear data combinations (principal components (PC). We calculated CB scores for each hospital as a sum of standardized values for each component multiplied by the respective PC loading. We evaluated the correlation of sepsis volume and each CB score with hospital mortality and with outward sepsis transfer proportions. We fitted linear, nested, predictive models to compare the system predictive abilities of CB scores and sepsis volume in relation to hospital mortality. RESULTS/ANTICIPATED RESULTS: In the derivation cohort, 83963 (93.2%) patients were non-transferred, of which 20230 (24.1%) died. The mean (range) score was 0 (-3 - +5) with higher scores denoting more capable hospitals. Higher scores were weakly and inversely correlated (spearman’s [r]: - 0.28) with outward sepsis transfer proportions. Higher scores had weak but better positive correlation with hospital mortality (r: 0.33), than sepsis volume (r: 0.24). CB scores explained more variation in sepsis mortality (R2 = 0.24, P DISCUSSION/SIGNIFICANCE: Capability-based hospital scores account for three times more variation in sepsis mortality than sepsis volume and outperform sepsis volume as a system predictor of mortality. With further refinement and validation, these scores may find utility for improving system-based approaches to sepsis care.

Introduction Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention.Methods The intervention is a deimplementation programme called DRAUP (deimplementation of routine chest radiographs after adoption of ultrasound-guided insertion and confirmation of central venous catheter protocol) that will be created to address one unnecessary imaging modality in the acute care environment. We propose a three-phase approach to changing low-value practices. In phase 1, we will be guided by the Consolidated Framework for Implementation Research framework to explore barriers and facilitators of POCUS for CVC confirmation in a single centre, large tertiary, academic hospital via focus groups. The qualitative methods will inform the development and adaptation of strategies that address identified determinants of change. In phase 2, the multifaceted strategies will be conceptualised using Morgan’s framework for understanding and reducing medical overuse. In phase 3, we will locally implement these strategies and assess them using Proctor’s outcomes (adoption, deadoption, fidelity and penetration) in an observational study to demonstrate proof of concept, gaining valuable insights on the programme. Secondary outcomes will include POCUS-guided CVC confirmation efficacy measured by time and effectiveness measured by sensitivity and specificity of POCUS confirmation after CVC insertion.With limited data available to inform interventions that use concurrent implementation and deimplementation strategies to substitute chest X-ray for POCUS using the DRAUP programme, we propose that this primary implementation and secondary effectiveness pilot study will provide novel data that will expand the knowledge of implementation approaches to replacing low value or unnecessary care in acute care environments.Ethics and dissemination Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means.Trial registration number ClinicalTrials.gov Identifier, NCT04324762, registered on 27 March 2020.

OBJECTIVES:. Telemedicine critical care is associated with improved efficiency, quality, and cost-effectiveness. As of 2010, fewer than 5% of U.S. hospitals had telemedicine critical care, and fewer than 10% of ICU beds were covered. We evaluated recent telemedicine critical care implementation and bed coverage rates in the United States and compared characteristics of hospitals with and without telemedicine critical care. DESIGN:. Cross-sectional study of 2018 American Hospital Association Annual Survey Database. SETTING:. U.S. hospitals. PATIENTS:. None. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We obtained data regarding telemedicine critical care implementation, ICU capability (defined as ≥ 1 ICU bed), other hospital characteristics, and the Herfindahl-Hirschman Index, a measure of ICU market competition based on hospital referral regions. Among 4,396 hospitals (response rate 71%), 788 (17.9%) had telemedicine critical care, providing potential coverage to 27,624 (28% of total) ICU beds. Among 306 hospital referral regions, 197 (64%) had a respondent hospital with telemedicine critical care. Telemedicine critical care implementation was associated with being a nonprofit (odds ratio, 7.75; 95% CI, 5.18–11.58) or public (odds ratio, 4.16 [2.57–6.73]) compared with for-profit hospital; membership in a health system (odds ratio, 3.83 [2.89–5.08]; stroke telemedicine presence (odds ratio, 6.87 [5.35–8.81]); ICU capability (odds ratio, 1.68 [1.25–2.26]); and more competitive ICU markets (odds ratio per 1,000-point decrease in Herfindahl-Hirschman Index 1.11 [1.01–1.22]). Notably, rural critical access hospitals had lower odds of telemedicine critical care implementation (odds ratio, 0.49 [0.34–0.70]). Teaching status, geographic region, and rurality were not associated with telemedicine critical care implementation. CONCLUSIONS:. About one fifth of respondent hospitals had telemedicine critical care by 2018, providing potential coverage of nearly one third of reported ICU beds. This represents a substantial increase in telemedicine critical care implementation over the last decade. Future expansion to include more rural hospitals that could benefit most may be aided by addressing hospital financial and market barriers to telemedicine critical care implementation.

The care of critically ill patients has become increasingly complex as severity of illness continues to increase, the number of patients requiring intensive care is on the rise, the amount of clinical information available at the bedside is growing, and the quantity of evidence supporting or refuting specific therapies and interventions for this population is escalating. It has become problematic for clinicians to master all of these tasks and to process the quantity of available clinical and scientific information in an effective and safe manner. Additionally, a culture promoting safety and accountability has emerged in the United States and throughout the world in regard to medical care. The expectation is that patients entering hospitals should receive the highest quality of care with minimal to no medical errors occurring. To accomplish this goal, as well as to allow more accurate monitoring of day to day medical practices, several strategies have been developed that have primarily been employed in the intensive care unit (ICU) setting. These strategies include the use of paper-based or electronic protocols for disease (e.g., severe sepsis and septic shock) or process of care (e.g., weaning of mechanical ventilation) management, national guidelines, and targeted clinician education with or without periodic feedback regarding compliance with best medical practices and resultant patient-based outcomes. This review focuses on the use of protocols in the ICU setting and how they can best be utilized to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To compare outcomes in patients with Staphylococcusaureus bacteraemia treated with linezolid with those of vancomycin-treated patients.Methods: We pooled and analysed five randomized studies comparing linezolid with vancomycin, focusing on the 144 adults with S. aureus bacteraemia, which was secondary in >70% of patients. Efficacy variables were clinical cure of primary infection, microbiological success (eradication of S. aureus from blood or presumed eradication based on clinical cure of primary infection), survival, and outcome predictors identified by multivariate logistic regression.Results: Of 99 clinically evaluable patients, primary infection was cured in 28 (55%) of 51 linezolid recipients and 25 (52%) of 48 vancomycin recipients [odds ratio (OR) for cure with linezolid versus vancomycin, 1.12; 95% confidence interval (CI), 0.51–2.47]. There were no between-group differences in the meta-analysis (OR, 1.16; 95% CI, 0.5–2.65). Of 53 evaluable patients with methicillin-resistant S. aureus (MRSA) bacteraemia, clinical cure occurred in 14 (56%) of 25 linezolid recipients and 13 (46%) of 28 vancomycin recipients (OR, 1.47; 95% CI, 0.50–4.34). Microbiological success occurred in 41 (69%) of 59 linezolid recipients and 41 (73%) of 56 vancomycin recipients (OR, 0.83; 95% CI, 0.37–1.87). Fifty-five (74%) of 74 linezolid recipients survived versus 52 (74%) of 70 vancomycin recipients (OR, 1.00; 95% CI, 0.47–2.12). In the multivariate analysis, treatment group was not a significant predictor of clinical cure or survival.Conclusions: Linezolid was associated with outcomes that were not inferior to those of vancomycin in patients with secondary S. aureus bacteraemia. [ABSTRACT FROM AUTHOR]

Background: Device-related pressure ulcers from noninvasive ventilation masks alter skin integrity and cause patients discomfort., Objective: To examine the incidence, location, and stage of pressure ulcers and patients' comfort with a nasal-oral mask compared with a full-face mask., Methods: A before-after study of a convenience sample of patients with noninvasive ventilation orders in 5 intensive care units was conducted. Two groups of 100 patients each received either the nasal-oral mask or the full-face mask. Skin was assessed before the mask was applied and every 12 hours after that or upon mask removal. Comfort levels were assessed every 12 hours on a Likert scale of 1 to 5 (1, most comfortable)., Results: A pressure ulcer developed in 20% of patients in the nasal-oral mask group and 2% of patients in the full-face mask group (P < .001). Comfort scores were significantly lower (more comfortable) with the full-face mask (mean [SD], 1.9 [1.1]) than with the nasal-oral mask (mean [SD], 2.7 [1.2], P < .001). Neither mean hours worn nor percentage adherence differed significantly: 28.9 (SD, 27.2) hours and 92% for full-face mask and 25 (SD, 20.7) and 92% for nasal-oral mask. No patients who had a pressure ulcer develop with the nasal-oral mask had a pressure ulcer develop with the full-face mask., Conclusion: The full-face mask resulted in significantly fewer pressure ulcers and was more comfortable for patients. The full-face mask is a reasonable alternative to traditional nasal-oral masks for patients receiving noninvasive ventilation., (©2015 American Association of Critical-Care Nurses.)