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Background: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more)., Methods: LoS outcomes were analysed descriptively in the pooled modified intention to treat (mITT) population (all patients who had a documented Candida infection in line with trial requirements and received at least one dose of study drug). In addition, to adjust for an imbalance between treatment groups in the proportion receiving mechanical ventilation at baseline, a generalised linear model with mechanical ventilation as a binary covariate was applied. Responses to an exploratory question in the phase 3 trial on possible earlier discharge with weekly rezafungin are also reported., Results: 294 patients were included (rezafungin 139, caspofungin 155), of whom 126 (43%) had ICU admission. Patients treated with rezafungin had a numerically shorter LoS than with caspofungin in all analyses. Mean total LoS was 25.2 days, vs 28.3 days with caspofungin, and mean ICU LoS was 16.1 vs 21.6 days for rezafungin and caspofungin, respectively. After adjustment for mechanical ventilation status the difference in ICU LoS was 4.1 days, a relative difference of 24% (95% CI -11%, 72%). Physicians would have considered earlier discharge for 16% of patients (30/187) with weekly rezafungin, an average of 5-6 days earlier., Conclusions: Rezafungin may enable shorter hospital and ICU LoS in IC/C compared with daily IV caspofungin, with accompanying savings in resource use. Further research is needed to confirm this in the real-world setting., Trial Registration: NCT03667690 (ReSTORE; September 12, 2018); NCT02734862 (STRIVE; April 12, 2016)., Competing Interests: Declarations Data and availability of materials Data supporting the findings of this study are available on request from Sara Dickerson, Sara.Dickerson@mundipharma.com. Ethics approval and consent to participate Both the STRIVE and ReSTORE trials were in conducted in accordance with current country and local regulations, the International Conference on Harmonisation Good Clinical Practice, and the Declaration of Helsinki. Ethics committees or institutional review boards at participating sites approved the protocols and all amendments. All patients, or their legally authorised representative, provided written informed consent. Consent for publication Not applicable. Competing interests PMH reports grants or contracts from Baxter, Cytosorbents, and Pfizer; consulting fees from Baxter, Cytosorbents, and Pfizer; honoraria from Baxter, and Cytosorbents; and support for attending meetings from Mundipharma, and Pfizer, outside of the submitted work. MB reports honoraria from and membership of data safety monitoring board or advisory board for Angelini, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi, outside of the submitted work. OAC reports grants or contracts from Amplyx, Basilea, Bundesministerium für Bildung und Forschung, Cidara, German Center for Infection Research, European Union Directorate-General for Research and Innovation (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, Noxxon, Octapharma, Pardes, Pfizer, Pharma Support America, Scynexis, and Seres; honoraria from Abbott, AbbVie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, and Shionogi; payment for expert testimony from Cidara; data safety monitoring board or advisory board membership for Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, Pharma Support America, Pulmocide, Shionogi, and The Prime Meridian Group; a patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); stocks from CoRe Consulting; outside of the submitted work. HD reports consulting fees from Pfizer, Gilead, MSD, Mundipharma, Shionogi, Viatris, outside of the submitted work. JF was an advisor/consultant and received grant support and honoraria for talks on behalf of Astellas Pharma, Gilead Sciences, Merck Sharp & Dohme and Pfizer, outside of the submitted work. MK reports grants from Barnes-Jewish Hospital Foundation and consulting fees from Merck, Pfizer, and Shionogi, outside of the submitted work. PP reports grants from Astellas, Gilead, Scynexis, and Cidara; fees for scientific advisory board from F2G, Matinas, TFF, Basilea outside of the submitted work. JP Reports no conflict of interest. JV reports consulting fees from and membership of data safety monitoring board or advisory board for F2G and consulting fees from Cidara and Scynexis, outside of the submitted work. IB and NM report being employees of Mundipharma. TS reports being an employee of and holding stocks in Cidara Therapeutics. GRT reports grants and consulting fees from Amplyx, Astellas, Cidara, F2G, and Manye; grants from Merck; and data safety monitoring board membership for Pfizer, outside of the submitted work., (© 2024. The Author(s).)

Objectives: Deep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown. Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial., Design: Pragmatic, multicenter ( n = 3), prospective before-after pilot and feasibility trial., Setting: The ED and ICUs at three medical centers., Patients: Consecutive, adult mechanically ventilation ED patients., Interventions: An educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome)., Measurements and Main Results: Sedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of -3 to -5 or a Sedation-Agitation Scale of 1-3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% ( p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group ( p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both., Conclusions: This pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes., Competing Interests: Drs. Fuller’s, Roberts’, and Mohr’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Fuller, Roberts, Mohr, Faine, and Yan received support for article research from the National Institutes of Health. Dr. Fuller is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R34HL150404. Dr. Kollef is supported by the Barnes-Jewish Hospital Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems to carry, as well as a lack of ED-based sedation trials, there is significant rationale to investigate ED-based sedation as a means to improve outcome., Methods and Analysis: This is a multicentre (n=3) prospective, before-and-after pilot trial examining the feasibility of implementing targeted sedation in the immediate postintubation period in the ED. A cohort of 344 patients receiving mechanical ventilation in ED will be included. Feasibility outcomes include: (1) participant recruitment; (2) proportion of Richmond Agitation-Sedation Scale (RASS) scores in the deep sedation range; (3) reliability (agreement) of RASS measurements performed by bedside ED nurses; and (4) adverse events. The proportion of deep sedation measurements before and after the intervention will be compared using the χ 2 test. Logistic regression will be used to compare before-and-after differences, adjusting for potential confounders. The inter-rater correlation coefficient will be used to assess paired observations between a study team member and bedside ED nurses, and to describe reliability of RASS measurements., Ethics and Dissemination: The Human Research Protection Office at Washington University in St. Louis School of Medicine has approved the study. The publication of peer-reviewed manuscripts and the presentation of abstracts at scientific meetings will be used to disseminate the work., Registration: ClinicalTrials.gov identifier NCT04410783; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials., Research Question: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia?, Study Design and Methods: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission., Results: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days., Interpretation: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes., Design: Multicenter, prospective cohort study., Setting: The emergency department and ICUs of 15 medical centers., Patients: Mechanically ventilated adult emergency department patients., Interventions: None., Measurements and Main Results: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73)., Conclusions: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Antibiotic resistance is recognized as a key determinant of outcome in patients with serious infections influencing empiric antibiotic practices especially for critically ill patients. Within the intensive care unit (ICU), nosocomial infections and increasingly community-onset infections are caused by multidrug-resistant bacteria. Escalating rates of antibiotic resistance adds substantially to the morbidity, mortality, and cost related to infections treated in the ICU. Both gram-positive organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and gram-negative bacteria, including Pseudomonas aeruginosa , Acinetobacter species, carbapenem-resistant Enterobacteriaceae , and extended spectrum β-lactamase producing organisms, are urgent threats. The rising rates of antimicrobial resistance have resulted in routine empiric administration of broad-spectrum antibiotics by clinicians to critically ill patients even when bacterial infection is microbiologically absent. Moreover, new broad-spectrum antibiotics are a challenge to use effectively while avoiding emergence of further resistance. Use of rapid diagnostic technologies (RDTs) will likely provide an important methodology for achieving this important balance. There is an urgent need for integrating the administration of new and existing antibiotics with RDTs in a way that is safe, cost-effective, applicable in all countries, and sustainable., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To use life cycle assessment to determine the environmental footprint of the care of patients with septic shock in the intensive care unit (ICU)., Design, Setting and Participants: Prospective, observational life cycle assessment examining the use of energy for heating, ventilation and air conditioning; lighting; machines; and all consumables and waste associated with treating ten patients with septic shock in the ICU at BarnesJewish Hospital, St. Louis, MO, United States (US-ICU) and ten patients at Footscray Hospital, Melbourne, Vic, Australia (Aus-ICU)., Main Outcome Measures: Environmental footprint, particularly greenhouse gas emissions., Results: Energy use per patient averaged 272 kWh/day for the US-ICU and 143 kWh/day for the Aus-ICU. The average daily amount of single-use materials per patient was 3.4 kg (range, 1.0-6.3 kg) for the US-ICU and 3.4 kg (range, 1.2-8.7 kg) for the Aus-ICU. The average daily particularly greenhouse gas emissions arising from treating patients in the US-ICU was 178 kg carbon dioxide equivalent (CO 2 -e) emissions (range, 165-228 kg CO 2 -e), while for the Aus-ICU the carbon footprint was 88 kg CO 2 -e (range, 77-107 kg CO 2 -e). Energy accounted for 155 kg CO 2 -e in the US-ICU (87%) and 67 kg CO 2 -e in the Aus-ICU (76%). The daily treatment of one patient with septic shock in the US-ICU was equivalent to the total daily carbon footprint of 3.5 Americans' CO 2 -e emissions, and for the Aus-ICU, it was equivalent to the emissions of 1.5 Australians., Conclusion: The carbon footprints of the ICUs were dominated by the energy use for heating, ventilation and air conditioning; consumables were relatively less important, with limited effect of intensity of patient care. There is large opportunity for reducing the ICUs' carbon footprint by improving the energy efficiency of buildings and increasing the use of renewable energy sources.

Background: Analgesia and sedation are cornerstone therapies for mechanically ventilated patients. Despite data showing that early deep sedation in the ICU influences outcome, this has not been investigated in the ED. Therefore, ED-based sedation practices, and their influence on outcome, remain incompletely defined. This study's objectives were to describe ED sedation practices in mechanically ventilated patients and to test the hypothesis that ED sedation depth is associated with worse outcomes., Methods: This was a cohort study of a prospectively compiled ED registry of adult mechanically ventilated patients at a single academic medical center. Hospital mortality was the primary outcome and hospital-, ICU-, and ventilator-free days were secondary outcomes. A backward stepwise multivariable logistic regression model evaluated the primary outcome as a function of ED sedation depth. Sedation depth was assessed with the Richmond Agitation-Sedation Scale (RASS)., Results: Four hundred fourteen patients were studied. In the ED, 354 patients (85.5%) received fentanyl, 254 (61.3%) received midazolam, and 194 (46.9%) received propofol. Deep sedation was observed in 244 patients (64.0%). After adjusting for confounders, a deeper ED RASS was associated with mortality (adjusted OR, 0.77; 95% CI, 0.63-0.94)., Conclusions: Early deep sedation is common in mechanically ventilated ED patients and is associated with worse mortality. These data suggest that ED-based sedation is a modifiable variable that could be targeted to improve outcome., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting., Methods: Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion., Results: The prevalence of infection of critically ill patients by MDR bacteria is rapidly evolving. Clinical studies aimed at improving understanding of the changing patterns of these infections in ICUs are urgently needed. Ideal antibiotic utilization is another area of uncertainty requiring additional investigations aimed at better understanding of dose optimization, duration of therapy, use of combination treatment, aerosolized antibiotics, and the integration of rapid diagnostics as a guide for treatment. Moreover, there is an imperative need to develop non-antibiotic approaches for the prevention and treatment of MDR infections in the ICU. Finally, clinical research aimed at demonstrating the beneficial impact of antimicrobial stewardship in the ICU setting is essential., Conclusions: These and other fundamental questions need to be addressed over the next decade in order to better understand how to prevent, diagnose, and treat MDR bacterial infections. Clinical studies described in this research agenda provide a template and set priorities for investigations that should be performed in this field.

Study Objective: We evaluated the efficacy of an emergency department (ED)-based lung-protective mechanical ventilation protocol for the prevention of pulmonary complications., Methods: This was a quasi-experimental, before-after study that consisted of a preintervention period, a run-in period of approximately 6 months, and a prospective intervention period. The intervention was a multifaceted ED-based mechanical ventilator protocol targeting lung-protective tidal volume, appropriate setting of positive end-expiratory pressure, rapid oxygen weaning, and head-of-bed elevation. A propensity score-matched analysis was used to evaluate the primary outcome, which was the composite incidence of acute respiratory distress syndrome and ventilator-associated conditions., Results: A total of 1,192 patients in the preintervention group and 513 patients in the intervention group were included. Lung-protective ventilation increased by 48.4% in the intervention group. In the propensity score-matched analysis (n=490 in each group), the primary outcome occurred in 71 patients (14.5%) in the preintervention group compared with 36 patients (7.4%) in the intervention group (adjusted odds ratio 0.47; 95% confidence interval [CI] 0.31 to 0.71). There was an increase in ventilator-free days (mean difference 3.7; 95% CI 2.3 to 5.1), ICU-free days (mean difference 2.4; 95% CI 1.0 to 3.7), and hospital-free days (mean difference 2.4; 95% CI 1.2 to 3.6) associated with the intervention. The mortality rate was 34.1% in the preintervention group and 19.6% in the intervention group (adjusted odds ratio 0.47; 95% CI 0.35 to 0.63)., Conclusion: Implementing a mechanical ventilator protocol in the ED is feasible and is associated with significant improvements in the delivery of safe mechanical ventilation and clinical outcome., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: Due to accuracy concerns, the Food and Drug Administration issued guidances to manufacturers that resulted in Center for Medicare and Medicaid Services stating that the use of meters in critically ill patients is "off-label" and constitutes "high complexity" testing. This is causing significant workflow problems in ICUs nationally. We wished to determine whether real-world accuracy of modern glucose meters is worse in ICU patients compared with non-ICU inpatients., Design: We reviewed glucose results over the preceding 3 years, comparing results from paired glucose meter and central laboratory tests performed within 60 minutes of each other in ICU versus non-ICU settings., Setting: Seven ICU and 30 non-ICU wards at a 1,300-bed academic hospital in the United States., Subjects: A total of 14,763 general medicine/surgery inpatients and 20,970 ICU inpatients., Interventions: None., Measurements and Main Results: Compared meter results with near simultaneously performed laboratory results from the same patient by applying the 2016 U.S. Food and Drug Administration accuracy criteria, determining mean absolute relative difference and examining where paired results fell within the Parkes consensus error grid zones. A higher percentage of glucose meter results from ICUs than from non-ICUs passed 2016 Food and Drug Administration accuracy criteria (p < 10) when comparing meter results with laboratory results. At 1 minute, no meter result from ICUs posed dangerous or significant risk by error grid analysis, whereas at 10 minutes, less than 0.1% of ICU meter results did, which was not statistically different from non-ICU results., Conclusions: Real-world accuracy of modern glucose meters is at least as accurate in the ICU setting as in the non-ICU setting at our institution.

Purpose: To review the salient features of the diagnosis and management of the most common skin and soft tissue infections (SSTI). This review focuses on severe SSTIs that require care in an intensive care unit (ICU), including toxic shock syndrome, myonecrosis/gas gangrene, and necrotizing fasciitis., Methods: Guidelines, expert opinion, and local institutional policies were reviewed., Results: Severe SSTIs are common and their management complex due to regional variation in predominant pathogens and antimicrobial resistance patterns, as well as variations in host immune responses. Unique aspects of care for SSTIs in the ICU are discussed, including the role of prosthetic devices, risk factors for bacteremia, and the need for surgical consultation. SSTI mimetics, the role of dermatologic consultation, and the unique features of SSTIs in immunocompromised hosts are also described., Conclusions: We provide recommendations for clinicians regarding optimal SSTI management in the ICU setting.

In 2013, a before-and-after intervention study was conducted to evaluate the effect 24-hour intensivist coverage on length of stay and rates of catheter-associated urinary tract infection, central-line associated blood stream infection, and ventilator-associated events. Intensivist coverage for 24 hours did not decrease length of stay or result in a decrease in any specific infection rate.

Over the last few decades, machine learning and data mining have been increasingly used for clinical prediction in ICUs. However, there is still a huge gap in making full use of the time-series data generated from ICUs. Aiming at filling this gap, we propose a novel approach entitled Time Slicing Cox regression (TS-Cox), which extends the classical Cox regression into a classification method on multi-dimensional time-series. Unlike traditional classifiers such as logistic regression and support vector machines, our model not only incorporates the discriminative features derived from the time-series, but also naturally exploits the temporal orders of these features based on a Cox-like function. Empirical evaluation on MIMIC-II database demonstrates the efficacy of the TS-Cox model. Our TS-Cox model outperforms all other baseline models by a good margin in terms of AUC&#95;PR, sensitivity and PPV, which indicates that TS-Cox may be a promising tool for mortality prediction in ICUs.

Infections with multidrug-resistant organisms (MDROs) are common in critically ill patients and are challenging to manage appropriately. Strategies that can be used in the treatment of MDRO infections in the intensive care unit (ICU) include combination therapy, adjunctive aerosolized therapy, and optimization of pharmacokinetics with higher doses or extended-infusion therapy as appropriate. Rapid diagnostic tests could assist in improving timely appropriate antimicrobial therapy for MDRO infections in the ICU., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of sepsis classification and multidrug-resistance status on outcome in patients receiving appropriate initial antibiotic therapy., Design: A retrospective cohort study., Setting: Barnes-Jewish Hospital, a 1,250-bed teaching hospital., Patients: Individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013., Interventions: Clinical outcomes were compared according to multidrug-resistance status, sepsis classification, demographics, severity of illness, comorbidities, and antimicrobial treatment., Measurements and Main Results: We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Mortality increased significantly with increasing severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic shock, respectively; p < 0.05). Time to antimicrobial therapy was not significantly associated with outcome. Acute Physiology and Chronic Health Evaluation II was more predictive of mortality than age-adjusted Charlson comorbidity index. Multidrug-resistance status did not result in excess mortality. Length of ICU and hospital stay increased with more severe sepsis. In multivariate logistic regression analysis, African-American race, sepsis severity, Acute Physiology and Chronic Health Evaluation II score, solid-organ cancer, cirrhosis, and transfer from an outside hospital were all predictors of mortality., Conclusions: Our results support sepsis severity, but not multidrug-resistance status as being an important predictor of death when all patients receive appropriate initial antibiotic therapy. Future sepsis trials should attempt to provide appropriate antimicrobial therapy and take sepsis severity into careful account when determining outcomes.

Background: The Centers for Disease Control and Prevention has shifted policy away from using ventilator-associated pneumonia (VAP) and toward using ventilator-associated conditions (VACs) as a marker of ICU quality. To date, limited prospective data regarding the incidence of VAC among medical and surgical ICU patients, the ability of VAC criteria to capture patients with VAP, and the potential clinical preventability of VACs are available., Methods: This study was a prospective 12-month cohort study (January 2013 to December 2013)., Results: We prospectively surveyed 1,209 patients ventilated for ≥ 2 calendar days. Sixty-seven VACs were identified (5.5%), of which 34 (50.7%) were classified as an infection-related VAC (IVAC) with corresponding rates of 7.0 and 3.6 per 1,000 ventilator days, respectively. The mortality rate of patients having a VAC was significantly greater than that of patients without a VAC (65.7% vs 14.4%, P < .001). The most common causes of VACs included IVACs (50.7%), ARDS (16.4%), pulmonary edema (14.9%), and atelectasis (9.0%). Among IVACs, 44.1% were probable VAP and 17.6% were possible VAP. Twenty-five VACs (37.3%) were adjudicated to represent potentially preventable events. Eighty-six episodes of VAP occurred in 84 patients (10.0 of 1,000 ventilator days) during the study period. The sensitivity of the VAC criteria for the detection of VAP was 25.9% (95% CI, 16.7%-34.5%)., Conclusions: Although relatively uncommon, VACs are associated with greater mortality and morbidity when they occur. Most VACs represent nonpreventable events, and the VAC criteria capture a minority of VAP episodes.

Objectives: Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients., Design: A retrospective cohort study., Setting: ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period., Patients: All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion., Interventions: None., Measurements and Main Results: A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p < 0.001), and the median hospital (23 d vs 15 d, p < 0.001) and ICU length of stay (12 d vs 8 d, p < 0.001) were found to be significantly longer in patients with C. difficile infection., Conclusions: Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

Background: With limited numbers of intensive care unit (ICU) beds available, increasing patient acuity is expected to contribute to episodes of inpatient deterioration on general wards., Objective: To prospectively validate a predictive algorithm for clinical deterioration in general-medical ward patients, and to conduct a trial of real-time alerts based on this algorithm., Design: Randomized, controlled crossover study., Setting/patients: Academic center with patients hospitalized on 8 general wards between July 2007 and December 2011., Interventions: Real-time alerts were generated by an algorithm designed to predict the need for ICU transfer using electronically available data. The alerts were sent by text page to the nurse manager on intervention wards., Measurements: Intensive care unit transfer, hospital mortality, and hospital length of stay., Results: Patients meeting the alert threshold were at nearly 5.3-fold greater risk of ICU transfer (95% confidence interval [CI]: 4.6-6.0) than those not satisfying the alert threshold (358 of 2353 [15.2%] vs 512 of 17678 [2.9%]). Patients with alerts were at 8.9-fold greater risk of death (95% CI: 7.4-10.7) than those without alerts (244 of 2353 [10.4%] vs 206 of 17678 [1.2%]). Among patients identified by the early warning system, there were no differences in the proportion of patients who were transferred to the ICU or who died in the intervention group as compared with the control group., Conclusions: Real-time alerts were highly specific for clinical deterioration resulting in ICU transfer and death, and were associated with longer hospital length of stay. However, an intervention notifying a nurse of the risk did not result in improvement in these outcomes., (Copyright © 2013 Society of Hospital Medicine.)

Antimicrobial stewardship involves a multifaceted approach aimed at combating the emergence of antibiotic resistance, improving patient outcomes, and controlling healthcare costs by optimizing antimicrobial use. Therefore, stewardship is of great importance and relevance in the ICU. The rapid pace of escalating antibiotic resistance and the widespread use of antibiotics in critical care require that stewardship programs be routinely employed in the ICU setting.

Background: Dexmedetomidine, a selective α2 adrenergic receptor agonist, exhibits sedative, analgesic, anxiolytic, and sympatholytic effects, and may aid in controlling agitation in the intensive care unit (ICU). At our hospital (Barnes-Jewish Hospital, St. Louis, MO), dexmedetomidine is commonly used as a sedative in the medical ICU. Predictors of dexmedetomidine intolerance or failure have not yet been defined., Objective: Describe the rate of dexmedetomidine infusion intolerance/failure and identify patient predictors of intolerance/failure., Methods: This retrospective single-center cohort study evaluated 75 mechanically ventilated adults who received dexmedetomidine infusion. Patients were included in the study if they were aged ≥ 18 years; mechanically ventilated for > 24 hours; received dexmedetomidine infusion for ≥ 1 hour following > 24 hours of continuous infusions of midazolam, fentanyl, or propofol; and were admitted to our medical ICU between August 1, 2009 and August 1, 2010. Multivariate logistic regression analysis was performed to identify independent predictors of intolerance/failure., Results: A total of 85 episodes of dexmedetomidine infusion were analyzed (75 total patients). Eighteen episodes (21%) met the criteria for intolerance/failure and 67 episodes (79%) met the criteria for tolerance/success. The median duration of mechanical ventilation, total dexmedetomidine infusion time, and ICU length of stay did not differ between groups. Nonblack race was the only variable independently associated with treatment failure or intolerance in the logistic regression analysis., Conclusion: Twenty-one percent of dexmedetomidine infusion episodes met the criteria for intolerance/failure. No predictors of intolerance/failure were found to be clinically significant.

Antimicrobial stewardship encompasses the optimization of agent selection, dose, and duration leading to the best clinical outcome in the treatment or prevention of infection. Ideally, these goals are met while producing the fewest side effects and lowest risk for subsequent resistance. The concept of antimicrobial stewardship can be directly applied to the prescription of empirical antibiotic therapy in the intensive care unit (ICU) because it is well described that inappropriate initial regimens lead to increased mortality. As such, care should be taken to identify factors that place patients at risk for infection with pathogens demonstrating reduced susceptibility or multidrug resistance. Research efforts have concentrated on molecular diagnostic techniques to aid in more rapid organism detection and thus potential for earlier therapy appropriateness and deescalation, although limitations prohibiting widespread implementation of this technology exist. Also of great importance with regard to stewardship efforts is infection prevention. Effective prophylactic strategies reduce the occurrence of nosocomial infections and may therefore improve patient outcomes while obviating the need for otherwise necessary antimicrobial exposure., (© Thieme Medical Publishers.)

Background: Nosocomial pneumonia is a difficult diagnosis to establish in the intensive care unit setting, due to the non-specific nature of the clinical and radiographic findings. Procalcitonin is a circulating biomarker that may become elevated in the presence of bacterial infection., Methods: We conducted a prospective single-center cohort study at Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital in St Louis, Missouri. In medical and surgical intensive care unit patients with suspected nosocomial pneumonia we measured plasma procalcitonin with an enzyme-linked fluorescent assay., Results: We evaluated 104 consecutive patients with suspected nosocomial pneumonia, 67 (64%) of whom met our predefined clinical and microbiologic criteria for definite nosocomial pneumonia. Though the mean procalcitonin concentration was greater in the 67 patients with definite nosocomial pneumonia (18.3 ± 99.1 ng/mL, median 0.8 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 43.1 ng/mL) than in the 12 patients with definite absence of nosocomial pneumonia (1.7 ± 2.0 ng/mL, median 1.0 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 6.7 ng/mL), this difference was not statistically significant (P = .66). A procalcitonin cutoff value of > 1 ng/mL yielded a diagnostic sensitivity of 50% and a specificity of 49% for definite nosocomial pneumonia. Receiver operating curve and multivariate logistic regression analyses demonstrated that procalcitonin is inferior to clinical variables for diagnosing nosocomial pneumonia. However, compared to patients with an initial procalcitonin > 1 ng/mL, those with lower procalcitonin had fewer total antibiotic days (13.0 ± 10.3 d vs 19.7 ± 12.0 d, P < .001) and fewer antibiotic days for treatment of nosocomial pneumonia (10.0 ± 5.9 d vs 14.7 ± 7.4 d, P < .001)., Conclusions: Plasma procalcitonin has minimal diagnostic value for nosocomial pneumonia.

Background: Ventilator-associated tracheobronchitis (VAT) is considered an intermediate condition between bacterial airway colonization and ventilator-associated pneumonia (VAP). The purpose of this prospective cohort study was to further characterize VAT in terms of incidence, etiology, and impact on patient outcomes., Methods: Patients intubated for >48 h in the surgical and medical ICUs of Barnes-Jewish Hospital were screened daily for the development of VAT and VAP over 1 year. Patients were followed until hospital discharge or death, and patient demographics, causative pathogens, and clinical outcomes were recorded., Results: A total of 28 patients with VAT and 83 with VAP were identified corresponding to frequencies of 1.4% and 4.0%, respectively. VAP was more common in surgical than medical ICU patients (5.3% vs 2.3%; P<.001), but the occurrence of VAT was similar between surgical and medical patients (1.3% vs 1.5%; P=.845). VAT progressed to VAP in nine patients (32.1%) despite antibiotic therapy. There was no significant difference in hospital mortality between patients with VAP and VAT (19.3% vs 21.4%; P=.789). VAT was caused by a multidrug-resistant (MDR) pathogen in nine cases (32.1%)., Conclusion: VAT occurs less commonly than VAP but at a similar incidence in medical and surgical ICU patients. VAT frequently progressed to VAP, and patients diagnosed with VAT had similar outcomes to those diagnosed with VAP, suggesting that antimicrobial therapy is appropriate for VAT. VAT is also frequently caused by MDR organisms, and this should be taken into account when choosing antimicrobial therapy.

Objective: To test whether intensive care unit (ICU) nasal screening for methicillin-resistant Staphylococcus aureus (MRSA) predicts the presence or absence of MRSA infections requiring antimicrobial treatment., Design: A prospective cohort study., Setting: Medical ICU at Barnes-Jewish Hospital, a 1252-bed urban teaching hospital., Patients: Seven hundred forty-nine consecutive patients admitted to the medical ICU over a 7-mo period (November 2007 through June 2008)., Interventions: Nasal swabs were obtained at ICU admission and weekly thereafter for MRSA detection by using polymerase chain reaction. All subjects were followed for the development of MRSA infection during their ICU stay., Measurements and Main Results: One hundred sixty-four (21.9%) patients had positive nasal colonization with MRSA at the time of ICU admission. The predictive accuracy of MRSA nasal colonization for ICU-acquired MRSA infections, either lower respiratory tract infection or bloodstream infection, was poor (lower respiratory tract infection: sensitivity, 24.2%; specificity, 78.5%; positive predictive value, 17.7%; and negative predictive value, 84.4%; and bloodstream infection: sensitivity, 23.1%; specificity, 78.2%; positive predictive value, 11.0%; and negative predictive value, 89.7%). Addition of nasal-colonization results obtained during the ICU stay did not appreciably change the predictive accuracy of this test for identification of subsequent lower respiratory tract infections and bloodstream infections attributed to MRSA requiring antimicrobial treatment., Conclusions: In this analysis, nasal colonization with MRSA was found to be a poor predictor for the subsequent occurrence of MRSA lower respiratory tract infections and MRSA bloodstream infections requiring antimicrobial treatment. Clinicians should be cautious in using the results of nasal-colonization testing to determine the need for MRSA treatment among patients with ICU-acquired infections.

Nosocomial pneumonia (NP) is a difficult diagnosis to establish in the critically ill patient due to the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. Additionally, the classification of NP in the intensive care unit setting has become increasingly complex, as the types of patients who develop NP become more diverse. The occurrence of NP is especially problematic as it is associated with a greater risk of hospital mortality, longer lengths of stay on mechanical ventilation and in the intensive care unit, a greater need for tracheostomy, and significantly increased medical care costs. The adverse effects of NP on healthcare outcomes has increased pressure on clinicians and healthcare systems to prevent this infection, as well as other nosocomial infections that complicate the hospital course of patients with respiratory failure. This manuscript will provide a brief overview of the current approaches for the diagnosis of NP and focus on strategies for prevention. Finally, we will provide some guidance on how standardized or protocolized care of mechanically ventilated patients can reduce the occurrence of and morbidity associated with complications like NP.

Background: Staphylococcus aureus is an important cause of infection in intensive care unit (ICU) patients. Colonization with methicillin-resistant S. aureus (MRSA) is a risk factor for subsequent S. aureus infection. However, MRSA-colonized patients may have more comorbidities than methicillin-susceptible S. aureus (MSSA)-colonized or noncolonized patients and therefore may be more susceptible to infection on that basis., Objective: To determine whether MRSA-colonized patients who are admitted to medical and surgical ICUs are more likely to develop any S. aureus infection in the ICU, compared with patients colonized with MSSA or not colonized with S. aureus, independent of predisposing patient risk factors., Design: Prospective cohort study., Setting: A 24-bed surgical ICU and a 19-bed medical ICU of a 1,252-bed, academic hospital., Patients: A total of 9,523 patients for whom nasal swab samples were cultured for S. aureus at ICU admission during the period from December 2002 through August 2007., Methods: Patients in the ICU for more than 48 hours were examined for an ICU-acquired S. aureus infection, defined as development of S. aureus infection more than 48 hours after ICU admission., Results: S. aureus colonization was present at admission for 1,433 (27.8%) of 5,161 patients (674 [47.0%] with MRSA and 759 [53.0%] with MSSA). An ICU-acquired S. aureus infection developed in 113 (2.19%) patients, of whom 75 (66.4%) had an infection due to MRSA. Risk factors associated with an ICU-acquired S. aureus infection included MRSA colonization at admission (adjusted hazard ratio, 4.70 [95% confidence interval, 3.07-7.21]) and MSSA colonization at admission (adjusted hazard ratio, 2.47 [95% confidence interval, 1.52-4.01])., Conclusion: ICU patients colonized with S. aureus were at greater risk of developing a S. aureus infection in the ICU. Even after adjusting for patient-specific risk factors, MRSA-colonized patients were more likely to develop S. aureus infection, compared with MSSA-colonized or noncolonized patients.

Antimicrobial stewardship involves a multifaceted approach that strives to combat the emergence of resistance, improve clinical outcomes, and control costs by improving antimicrobial use. Therefore, stewardship is of great importance and relevance in the intensive care unit. Clinical decision support systems, biomarker-derived treatment algorithms, and improved knowledge regarding the different components of antimicrobial therapy represent some of the advances that have been made in stewardship. Yet, significant obstacles have prevented the full achievement of stewardship's goals, and approaches to confronting these obstacles should be appreciated. Clinicians should realize that antimicrobials are important therapeutic agents and strive to use them wisely.

Objective: Ventilator-associated pneumonia (VAP) is a target for health care quality improvement. The Institute for Healthcare Improvement has led the charge with its ventilator bundle aimed at VAP prevention. We set out to review the literature on the effectiveness of the bundle to prevent VAP., Design: Systematic literature review., Setting: Intensive care unit., Measurements and Main Results: We identified four studies that met the inclusion criteria. The review revealed major methodologic flaws in design, reporting and results of the studies, including bias, confounding, and lack of generalizability., Conclusion: Lack of methodologic rigor of the reported studies precludes any conclusive statements about the bundle's effectiveness or cost-effectiveness. To assure efficient allocation of the limited healthcare resources, rigorous evaluation of optimal strategies for VAP prevention is needed to 1) establish best practices and 2) create a benchmark against which new technologies' value can be assessed. The vent bundle is not a viable quality measure in the intensive care unit at this time.

Methicillin-resistant Staphylococcus aureus (MRSA) displays a remarkable array of resistance and virulence factors, which have contributed to its prominent role in infections of the critically ill. We are beginning to understand the function and regulation of some of these factors and efforts are ongoing to better characterize the complex interplay between the microorganism and host response. It is important that clinicians recognize the changing resistance patterns and epidemiology of Staphylococcus spp., as these factors may impact patient outcomes. Community-associated MRSA clones have emerged as an increasingly important subset of Staphyloccocus aureus and MRSA can no longer be considered as solely a nosocomial pathogen. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has long been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for existing and investigational agents demonstrating efficacy in this role.

Introduction: The assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness., Methods: Medical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness., Results: A total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by > or =15% after volume infusion (responders). A SV increase induced by PLR of > or =15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%., Conclusions: Non-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.

Probiotics are living microorganisms that, when administered in adequate amounts, confer health benefits on the host. Because probiotics are not marketed as pharmaceuticals, they are commercially available without rigorous scientific documentation of their efficacy for many health-related claims. Results from existing clinical trials are both confusing and controversial. The evidence base is relatively limited, includes studies with varied designs, assesses multiple probiotic preparations across discrepant disease states, and provides conflicting results. Recent advances in the delineation of probiotics' mechanisms of action offer the opportunity to construct a more logical framework within which future trials are designed.

Objective: To examine the 30-day mortality rate among patients with Clostridium difficile-associated disease (CDAD) requiring intensive care., Design: A retrospective, single-center, observational, cohort study., Setting: Barnes-Jewish Hospital, a 1,200-bed, urban, teaching facility., Patients: Adult patients admitted to the ICU identified to have CDAD by enzyme immunoassay., Interventions: Retrospective data collection from automated hospital, microbiology, and pharmacy databases., Measurements and Main Results: Two hundred seventy-eight patients with CDAD admitted to an ICU were identified over a 2-year period. Two hundred six patients (74.1%) received prior antibiotic therapy. The overall 30-day mortality rate was 36.7% (n = 102). Logistic regression analysis identified septic shock (adjusted odds ratio, 1.96; 95% confidence interval [CI], 1.47 to 2.61; p = 0.018), ward-to-ICU transfer (adjusted odds ratio, 2.12; 95% CI, 1.62 to 2.79; p = 0.006), and increasing APACHE (acute physiology and chronic health evaluation) II scores (1-point increments) [adjusted odds ratio, 1.09; 95% CI, 1.07 to 1.12; p < 0.001] as independent predictors for 30-day mortality. The attributable mortality associated with CDAD was estimated to be 6.1% (95% CI, - 1.7 to 13.9%; p = 0.127). CDAD was associated with an excess ICU length of stay (2.2 days) and hospital length of stay (4.5 days)., Conclusions: We found a high 30-day crude mortality among patients with CDAD in the ICU setting. Although the attributable mortality from CDAD was relatively low, excess length of stay in the ICU and hospital was observed with CDAD. ICUs should routinely employ infection control efforts aimed at minimizing the occurrence of CDAD because of the excess morbidity associated with this nosocomial infection.

Objective: To increase patient safety event reporting in three intensive care units (ICUs) using a new voluntary card-based event reporting system and to compare and evaluate observed differences in reporting among healthcare workers across ICUs., Design: Prospective, single-center, interventional study., Setting: A medical ICU (19 beds), surgical ICU (24 beds), and cardiothoracic ICU (17 beds) at a 1,371-bed urban teaching hospital., Patients: Adult patients admitted to these three study ICUs., Interventions: Use of a new, internally designed, card-based reporting program to solicit voluntary anonymous reporting of medical errors and patient safety concerns., Measurements and Main Results: During a 14-month period, 714 patient safety events were reported using a new card-based reporting system, reflecting a significant increase in reporting compared with pre-intervention Web-based reporting (20.4 reported events/1,000 patient days pre-intervention to 41.7 reported events/1,000 patient days postintervention; rate ratio, 2.05; 95% confidence interval, 1.79-2.34). Nurses submitted the majority of reports (nurses, 67.1%; physicians, 23.1%; other reporters, 9.5%); however, physicians experienced the greatest increase in reporting among their group (physicians, 43-fold; nurses, 1.7-fold; other reporters, 4.3-fold) relative to pre-intervention rates. There were significant differences in the reporting of harm by job description: 31.1% of reports from nurses, 36.2% from other staff, and 17.0% from physicians described events that did not reach/affect the patient (p = .001); and 33.9% of reports from physicians, 27.2% from nurses, and 13.0% from other staff described events that caused harm (p = .005). Overall reported patient safety events per 1,000 patient days differed by ICU (medical ICU = 55.5, cardiothoracic ICU = 25.3, surgical ICU = 40.2; p < .001)., Conclusions: This card-based reporting system increased reporting significantly compared with pre-intervention Web-based reporting and revealed significant differences in reporting by healthcare worker and ICU. These differences may reveal important preferences and priorities for reporting medical errors and patient safety events.

Objective: To evaluate the epidemiology, outcomes, and importance of Clostridium difficile colonization pressure (CCP) as a risk factor for C. difficile-associated disease (CDAD) acquisition in intensive care unit (ICU) patients., Design: Secondary analysis of data from a 30-month retrospective cohort study., Setting: A 19-bed medical ICU in a midwestern tertiary care referral center., Patients: Consecutive sample of adult patients with a length of stay of 24 hours or more between July 1, 1997, and December 31, 1999., Results: Seventy-six (4%) of 1,872 patients were identified with CDAD; 40 (53%) acquired CDAD in the ICU, for an incidence of 3.2 cases per 1,000 patient-days. Antimicrobial therapy, enteral feeding, mechanical ventilation, vancomycin-resistant enterococci (VRE) colonization or infection, and CCP (5.5 vs 2.0 CDAD case-days of exposure for patients with acquired CDAD vs no CDAD; P=.001) were associated with CDAD acquisition in the univariate analysis. Only VRE colonization or infection (45% of patients with acquired CDAD vs 16% of patients without CDAD; adjusted odds ratio, 2.76 [95% confidence interval, 1.36-5.59]) and a CCP of more than 30 case-days of exposure (20% with acquired CDAD vs 2% with no CDAD; adjusted odds ratio, 3.77 [95% confidence interval, 1.14-12.49]) remained statistically significant in the multivariable analysis. Lengths of stay (6.1 vs 3.0 days; P<.001 by univariate analysis) and ICU costs ($11,353 vs $6,028; P<.001 by univariate analysis) were higher for patients with any CDAD than for patients with no CDAD., Conclusions: In this nonoutbreak setting, the CCP was an independent risk factor for acquisition of CDAD in the ICU at the upper range of exposure duration. Having CDAD in the ICU was a marker of excess healthcare use.

Background: Antimicrobial-resistant organisms are an emerging problem in the ICU. Therapy cycling empiric antibiotics between various classes may influence bacterial resistance patterns. Understanding the impact of cycling on the appropriate treatment of suspected Gram-negative infections is important., Methods: Data were prospectively collected on patients who were admitted to a 19-bed medical ICU (MICU). A total of 1,172 patients were admitted to the MICU for > 48 h and were evaluated during a 28.5-month period. After 4.5 months of baseline data collection, an antibiotic-cycling protocol was implemented, using four different antibiotic classes with Gram-negative activity that were cycled every 3 to 4 months. Therapy was considered to be inappropriate if the subsequent bacterial isolate was resistant to the empiric drug used., Results: There were 59 bloodstream infections (BSIs), 17 ventilator-associated pneumonias (VAPs), and 101 urinary tract infections (UTIs) involving Gram-negative bacteria among 139 patients. Fifty-five infections (31%) were due to Gram-negative bacteria resistant to one or more antibiotic agents (BSIs, 18 [30%]; VAPs, 4 [23%]; and UTIs, 33 [33%]). Fifteen patients received inappropriate empiral therapy for 18 resistant Gram-negative infections (BSIs, 7 [39%]; VAPs, 3 [75%]; UTIs, 8 [24%]). Patients receiving inappropriate therapy were more likely to die (10 patients [67%] vs 40 patients [32%], respectively; p < 0.01). There was no difference in the receipt of appropriate empirical antibiotic therapy during the baseline compared to cycling (infectious episodes, 15% vs 10%, respectively; p = 0.4)., Conclusions: Antimicrobial resistance occurred in almost 30% of ICU infections involving Gram-negative bacteria. Antibiotic cycling was not associated with significant changes in the receipt of appropriate empirical antimicrobial therapy for the treatment of ICU infections.

Antibiotic resistance has emerged as an important determinant of mortality for patients in the intensive care unit (ICU) setting. This is largely due to the increasing presence of pathogenic microorganisms with resistance to existing antibiotic agents, resulting in the administration of inappropriate treatment. Escalating antibiotic resistance has also been associated with greater overall health care costs, as a result of prolonged hospitalizations and convalescence associated with failure of antibiotic treatment, the need to develop new antibiotic agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens. Antibiotic cycling has been advocated as a tool to reduce the occurrence of antibiotic resistance, especially in the ICU setting. Unfortunately, the cumulative evidence to date suggests that antibiotic cycling has limited efficacy for preventing antibiotic resistance. Nevertheless, a strategy whereby multiple or all classes of antibiotics are available for use (i.e., antibiotic heterogeneity) can be part of a broader effort aimed at curtailing antibiotic resistance within ICUs. Such efforts should be routine, given the limited availability of new antibiotic drug classes for the foreseeable future.

Objective: To assemble the available clinical data on the prevention of antimicrobial resistance in the intensive care unit (ICU) setting., Data Source: A MEDLINE database search and references from identified articles were employed to obtain the literature relating to the prevention of antimicrobial resistance in the ICU., Conclusions: The ICU presents a unique environment for the conduct of clinical research. The closed physical space with centralized patient management and efficient data recovery allows important clinical questions to be evaluated in a timely manner. Antimicrobial resistance has emerged as an important determinant of mortality for patients in the ICU. Additionally, there is currently a limited pipeline of new agents for the treatment of emerging bacteria with new resistance genes that pose an increasing threat to the ICU patient. Effective strategies for the prevention of antimicrobial resistance within ICUs are available and should be implemented aggressively. These strategies can be divided into non-pharmacologic infection- control strategies (e.g., routine hand hygiene, infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotics, narrowing of the antimicrobial spectrum on the basis of culture results). Additional studies conducted in ICUs are needed urgently to identify the optimal approaches for the management of antibiotics in order to balance the need for efficacy with the ability to minimize resistance.

Antimicrobial resistance has emerged as one of the most important issues complicating the management of critically ill patients with infection. This is largely due to the increasing presence of pathogenic microorganisms with resistance to existing antimicrobial agents resulting in the administration of inappropriate treatment. Effective strategies for the prevention of antimicrobial resistance within intensive care units are available and should be aggressively implemented. The importance of preventing antimicrobial resistance is magnified by the limited availability of new antimicrobial drug classes for the foreseeable future.

Objective: To assemble the available clinical data for the prevention of antimicrobial resistance into practical recommendations for clinicians., Data Source: A Medline database and references from identified articles were employed to perform a literature search relating to the prevention of antimicrobial resistance., Conclusions: Antimicrobial resistance has emerged as an important determinant of mortality for patients in the intensive care unit. This is largely due to the increasing presence of pathogenic microorganisms with resistance to existing antimicrobial agents, resulting in the administration of inappropriate treatment. Effective strategies for the prevention of antimicrobial resistance within intensive care units are available and should be aggressively implemented. These strategies can be divided into nonpharmacologic infection control strategies (e.g., routine hand hygiene, implementation of infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotic treatment, narrowing of antimicrobial spectrum based on culture results). Increasing current efforts aimed at the prevention of antimicrobial resistance is especially important given the limited availability of new antimicrobial drug classes for the foreseeable future.