Long-Term Effects of a Stepwise, Multimodal, Non-Restrictive Antimicrobial Stewardship Programme for Reducing Broad-Spectrum Antibiotic Use in the ICU.

Information on the long-term effects of non-restrictive antimicrobial stewardship (AMS) strategies is scarce. We assessed the effect of a stepwise, multimodal, non-restrictive AMS programme on broad-spectrum antibiotic use in the intensive care unit (ICU) over an 8-year period. Components of the AMS were progressively implemented. Appropriateness of antibiotic prescribing was also assessed by monthly point-prevalence surveys from 2013 onwards. A Poisson regression model was fitted to evaluate trends in the reduction of antibiotic use and in the appropriateness of their prescription. From 2011 to 2019, a total of 12,466 patients were admitted to the ICU. Antibiotic use fell from 185.4 to 141.9 DDD per 100 PD [absolute difference, -43.5 (23%), 95% CI -100.73 to 13.73; p = 0.13] and broad-spectrum antibiotic fell from 41.2 to 36.5 [absolute difference, -4.7 (11%), 95% CI -19.58 to 10.18; p = 0.5]. Appropriateness of antibiotic prescribing rose by 11% per year [IRR: 0.89, 95% CI 0.80 to 1.00; p = 0.048], while broad-spectrum antibiotic use showed a dual trend, rising by 22% until 2015 and then falling by 10% per year since 2016 [IRR: 0.90, 95% CI 0.81 to 0.99; p = 0.03]. This stepwise, multimodal, non-restrictive AMS achieved a sustained reduction in broad-spectrum antibiotic use in the ICU and significantly improved appropriateness of antibiotic prescribing.

External ventriculostomy-associated infection reduction after updating a care bundle.

BACKGROUND: Despite the clinical benefits of external ventricular drains (EVD), these devices can lead to EVD-related infections (EVDRI). The drainage insertion technique and standardized guidelines can significantly reduce the risk of infection, mainly caused by gram-positive bacteria. However, gram-negative microorganisms are the most frequent causative microorganisms of EVDRI in our hospital. We aimed to determine whether a new bundle of measures for the insertion and maintenance of a drain could reduce the incidence of EVDRI. This cohort study of consecutive patients requiring EVD from 01/01/2015 to 12/31/2018 compared the patients' characteristics before and after introducing an updated protocol (UP) for EVD insertion and maintenance in 2017. RESULTS: From 204 consecutive patients, 198 requiring EVD insertion were included (54% females, mean age 55 ± 15 years). The before-UP protocol included 87 patients, and the after-UP protocol included 111 patients. Subarachnoid (42%) and intracerebral (24%) hemorrhage were the main diagnoses at admission. The incidence of EVDRI fell from 13.4 to 2.5 episodes per 1000 days of catheter use. Gram-negative bacteria were the most frequent causative microorganisms. Previous craniotomy remained the only independent risk factor for EVDRI. EVDRI patients had increased mechanical ventilation durations, hospital and ICU stays, and percutaneous tracheostomy requirements. CONCLUSIONS: A care bundle focusing on fewer catheter sampling and more accurate antiseptic measures can significantly decrease the incidence of EVDRI. After implementing the management protocol, a decreased incidence of infections caused by gram-negative and gram-positive bacteria and reduced ICU and hospital lengths of stay were observed.

Antimicrobial use and aetiology of bloodstream infections in critically ill patients during early stages of SARS-CoV-2 pandemic.

Background: During early stages of COVID-19 pandemic, antimicrobials were commonly prescribed. Aim: To describe clinical, microbiological and antimicrobial use changes in bloodstream infections (BSI) of ICU patients during the first wave of COVID-19 pandemic compared to pre-COVID-19 era. Methods: Observational cohort study of patients admitted to ICU of Bellvitge University Hospital was conducted during the COVID-19 pandemic (March-June 2020) and before COVID-19 pandemic (March-June 2019). Differences in clinical characteristics, antimicrobial consumption and incidence and aetiology of BSI were measured. Findings: COVID-19 patients had significantly less comorbidities with obesity the only risk factor that increased in frequency. COVID-19 patients more frequently required invasive supportive care measures, had longer median ICU stay and higher mortality rates. The incidence of BSIs was higher in COVID-19 period (RR 3.2 [95%CI 2.2-4.7]), occurred in patients who showed prolonged median ICU stay (21days) and was associated with high mortality rate (47%). The highest increases in the aetiological agents were observed for AmpC-producing bacteria (RR 11.1 [95%CI 2.6-47.9]) and non-fermenting rods (RR 7.0 [95%CI 1.5-31.4]). The emergence of bacteraemia caused by Gram-negative rods resistant to amoxicillin-clavulanate, which was used as empirical therapy during early stages of the pandemic, led to an escalation towards broader-spectrum antimicrobials such as meropenem and colistin which was also associated with the emergence of resistant isolates. Conclusions: The epidemiological shift towards resistant phenotypes in critically ill COVID-19 patients was associated with the selective use of antimicrobials. Our study provides evidence of the impact of empirical therapy on the selection of bacteria and their consequences on BSI over the subsequent months.

Radio-Histological Correlation of Lung Features in Severe COVID-19 Through CT-Scan and Lung Ultrasound Evaluation.

Background: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. Lung histological samples were scarce due to the high risk of contamination during autopsies. We aimed to correlate histological COVID-19 features with radiological findings through lung ultrasound (LU)-guided postmortem core needle biopsies (CNBs) and computerized tomography (CT) scans. Methodology: We performed an observational prospective study, including 30 consecutive patients with severe COVID-19. The thorax was divided into 12 explorations regions to correlate LU and CT-scan features. Histological findings were also related to radiological features through CNBs. Results: Mean age was 62.56 ± 13.27 years old, with 96.7% male patients. Postmortem LU-guided CNBs were performed in 13 patients. Thirty patients were evaluated with both thoracic LU and chest CT scan, representing a total of 279 thoracic regions explored. The most frequent LU finding was B2-lines (49.1%). The most CT-scan finding was ground-glass opacity (GGO, 29%). Pathological CT-scan findings were commonly observed when B2-lines or C-lines were identified through LU (positive predictive value, PPV, 87.1%). Twenty-five postmortem echo-guided histological samples were obtained from 12 patients. Histological samples showed diffuse alveolar damage (DAD) (75%) and chronic interstitial inflammation (25%). The observed DAD was heterogeneous, showing multiple evolving patterns of damage, including exudative (33.3%), fibrotic (33.3%), and organizing (8.3%) phases. In those patients with acute or exudative pattern, two lesions were distinguished: classic hyaline membrane; fibrin "plug" in alveolar space (acute fibrinous organizing pneumonia, AFOP). C-profile was described in 33.3% and presented histological signs of DAD and lung fibrosis. The predominant findings were collagen deposition (50%) and AFOP (50%). B2-lines were identified in 66.7%; the presence of hyaline membrane was the predominant finding (37.5%), then organizing pneumonia (12.5%) and fibrosis (37.5%). No A-lines or B1-lines were observed in these patients. Conclusion: LU B2-lines and C-profile are predominantly identified in patients with severe COVID-19 with respiratory worsening, which correspond to different CT patterns and histological findings of DAD and lung fibrosis.

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit.

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality.

Lung Ultrasound Score to Predict Outcomes in COVID-19.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. We aimed to study the potential role of lung ultrasound score (LUS) in subjects with COVID-19. METHODS: We conducted an observational, prospective pilot study, including consecutive subjects admitted to an intermediate care unit due to COVID-19 pneumonia. LUS is a 12-zone examination method for lung parenchyma assessment. LUS was performed with a portable convex transducer, scores from 0 to 36 points. Clinical and demographic data were collected at LUS evaluation. Survival analysis was performed using a composite outcome including ICU admission or death. Subjects were followed for 30 d from LUS assessment. RESULTS: Of 36 subjects included, 69.4% were male, and mean age was 60.19 ± 12.75 y. A cutoff LUS ≥ 24 points showed 100% sensitivity, 69.2% specificity, and an area under the receiver operating characteristic curve of 0.85 for predicting worse prognosis. The composite outcome was present in 10 subjects (55.6%) with LUS ≥ 24 points, but not in the group with lower LUS scores (P < .001). Subjects with LUS ≥ 24 points had a higher risk of ICU admission or death (hazard ratio 9.97 [95% CI 2.75-36.14], P < .001). Significant correlations were observed between LUS and [Formula: see text], serum D-dimer, C-reactive protein, lactate dehydrogenase, and lymphocyte count. CONCLUSIONS: LUS ≥ 24 points can help identify patients with COVID-19 who are likely to require ICU admission or to die during follow-up. LUS also correlates significantly with clinical and laboratory markers of COVID-19 severity.

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

The spatial parameters of gait and their association with falls, functional decline and death in older adults: a prospective study.

Association between spatial gait parameters and adverse health outcomes in the elderly has not been sufficiently studied. The goal of this study is to evaluate whether the stride length or the step width predict falls, functional loss and mortality. We conducted a prospective cohort study on a probabilistic sample of 431 noninstitutionalized, older-than-64-years subjects living in Spain, who were followed-up for five years. In the baseline visit, spatial gait parameters were recorded along with several control variables, with special emphasis on known medical conditions, strength, balance and functional and cognitive capacities. In the follow-up calls, vital status, functional status and number of falls from last control were recorded. We found that a normalized-to-height stride length shorter than 0.52 predicted recurrent falls in the next 6 months with 93% sensitivity and 53% specificity (AUC: 0.72), and in the next 12 months with 81% sensitivity and 57% specificity (AUC: 0.67). A normalized stride length <0.5 predicted functional loss at 12 months with a sensitivity of 79.4% and specificity of 65.6% (AUC: 0.75). This predictive capacity remained independent after correcting for the rest of risk factors studied. Step-with was not clearly related to functional loss or falls. Both shorter normalized stride length (OR1.56; AUC: 0.62; p < 0.05) and larger step width (OR1.42; AUC: 0.62; p < 0.05) were associated with risk of death at 60 months; however, none of them remained as independent predictor of death, after correcting for other risk factors. In summary, spatial gait parameters may be risk markers for adverse outcomes in the elderly. Step length is independently associated with functional loss and falls at one year, after correction for numerous known risk factors.

Normal limits of home measured spatial gait parameters of the elderly population and their association with health variables.

Gait studies in the elderly population have been always conducted in gait labs or spacious clinical facilities, which influence gait parameters, and also implies that the participants have to be able to move to these facilities. Indoors gait characteristics of the elderly population have been very little studied. In this study, we aim to define the normal limits of the spatial gait parameters of the elderly, when walking at home, and to analyze relationship existing between the spatial gait parameters to other health variables. For such purpose, we conducted a transversal study on a probabilistic sample of 431 Spanish community-dwelling older, in which the spatial gait parameters were recorded by using an ink footprints method. We found that the mean stride length indoors was 88.47 cm (SD:26.05 cm; mean CI95%:85.52-91.41 cm), and the mean step width was 10.34 cm (SD:4.37 cm; mean CI95%:9.84-10.83 cm). Stride length was shorter in women and the oldest group, and was significantly influenced by the strength, balance, and physical activity. Stride width was larger in the oldest group and mainly affected by balance. A composite parameter including width and normalized stride length was independent from sex, and strongly differentiated between age groups. This parameter was affected by strength.

Effects of an omega-3 fatty acid-enriched lipid emulsion on eicosanoid synthesis in acute respiratory distress syndrome (ARDS): A prospective, randomized, double-blind, parallel group study.

BACKGROUND: The use of lipid emulsions has been associated with changes in lung function and gas exchange which may be mediated by biologically active metabolites derived from arachidonic acid. The type and quantity of the lipid emulsions used could modulate this response, which is mediated by the eicosanoids. This study investigates the use of omega-3 fatty acid-enriched lipid emulsions in ARDS patients and their effects on eicosanoid values. METHODS: Prospective, randomized, double-blind, parallel group study carried out at the Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men; age: 58 ± 13 years; APACHE II score 17.8 ± 2.3; Lung Injury Score: 3.1 ± 0.5; baseline PaO2/FiO2 ratio: 149 ± 40). Patients were randomized into two groups: Group A (n = 8) received the study emulsion Lipoplus® 20%, B. Braun Medical (50% MCT, 40% LCT, 10% fish oil (FO)); Group B (n = 8) received the control emulsion Intralipid® Fresenius Kabi (100% LCT). Lipid emulsions were administered for 12 h at a dose of 0.12 g/kg/h. We measured LTB4, TXB2, and 6-keto prostaglandin F1α values at baseline [immediately before the administration of the lipid emulsions (T-0)], at the end of the administration (T-12) and 24 hours after the beginning of the infusion (T 24) in arterial and mixed venous blood samples. RESULTS: In group A (FO) LTB4, TXB2, 6-keto prostaglandin F1α levels fell during omega-3 administration (T12). After discontinuation (T24), levels of inflammatory markers (both systemic and pulmonary) behaved erratically. In group B (LCT) all systemic and pulmonary mediators increased during lipid administration and returned to baseline levels after discontinuation, but the differences did not reach statistical significance. There was a clear interaction between the treatment in group A (fish oil) and changes in LTB4 over time. CONCLUSIONS: Infusion of lipids enriched with omega-3 fatty acids produces significant short- term changes in eicosanoid values, which may be accompanied by an immunomodulatory effect. TRIAL REGISTRATION: ISRCTN63673813.

Effects on hemodynamics and gas exchange of omega-3 fatty acid-enriched lipid emulsion in acute respiratory distress syndrome (ARDS): a prospective, randomized, double-blind, parallel group study.

INTRODUCTION: We investigated the effects on hemodynamics and gas exchange of a lipid emulsion enriched with omega-3 fatty acids in patients with ARDS. METHODS: The design was a prospective, randomized, double-blind, parallel group study in our Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men and 2 women; mean age: 58 +/- 13 years; APACHE II score: 17.8 +/- 2.3; Lung Injury Score: 3.1 +/- 0.5; baseline PaO2/FiO2 ratio: 149 +/- 40). Patients were randomized into 2 groups: Group A (n = 8) received the study emulsion Lipoplus 20%, B.Braun Medical (50% MCT, 40% LCT, 10% omega-3); Group B (n = 8) received the control emulsion Intralipid Fresenius Kabi (100% LCT). Lipid emulsions were administered during 12 h at a dose of 0.12 g/kg/h. Measurements of the main hemodynamic and gas exchange parameters were made at baseline (immediately before administration of the lipid emulsions), every hour during the lipid infusion, at the end of administration, and six hours after the end of administration lipid infusion. RESULTS: No statistically significant changes were observed in the different hemodynamic values analyzed. Likewise, the gas exchange parameters did not show statistically significant differences during the study. No adverse effect attributable to the lipid emulsions was seen in the patients analyzed. CONCLUSION: The lipid emulsion enriched with omega-3 fatty acids was safe and well tolerated in short-term administration to patients with ARDS. It did not cause any significant changes in hemodynamic and gas exchange parameters. TRIAL REGISTRATION: ISRCTN63673813.

Possible prognostic value of leukotriene B(4) in acute respiratory distress syndrome.

OBJECTIVE: To study the major eicosanoids implicated in the pathophysiology of acute respiratory distress syndrome (ARDS) in order to estimate their relative prognostic values. METHODS: We conducted a prospective study in a consecutive series of patients with ARDS admitted to a university hospital intensive care unit. We measured the plasma concentrations of 3 inflammatory mediators (thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4)) in peripheral arterial and mixed venous plasma samples. RESULTS: We studied 16 patients with ARDS, who had a mean alpha SD baseline ratio of P(aO(2)) to fraction of inspired oxygen (P(aO(2))/F(IO(2))) of 147 +/- 37 mm Hg and a mean +/- SD baseline lung injury score of 2.9 +/- 0.37. The plasma concentrations of thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4) were greater than the general-population reference levels in both arterial and mixed venous plasma, but only leukotriene B(4) was higher in arterial plasma than in mixed venous plasma (401 +/- 297 pg/mL vs 316 +/- 206 pg/mL, p = 0.04). When we correlated the eicosanoid concentrations with specific indicators of clinical severity, we found correlations only between the baseline P((aO2))/F(IO(2)) and the arterial thromboxane B(2) level (r = -0.57, p = 0.02), the arterial leukotriene B(4) level (r = -0.59, p = 0.01), and the transpulmonary gradient of leukotriene B(4) level (r = -0.59, p = 0.01). We also found a correlation between the transpulmonary gradient of leukotriene B(4) and the lung injury score (r = 0.51, p = 0.04). The thromboxane B(2) concentration in arterial plasma and the leukotriene B(4) concentration in both arterial and mixed venous plasma were the only baseline plasma eicosanoid concentrations that predicted significant differences in outcome. When looking at the transpulmonary gradient of the eicosanoids studied, we found that only the gradient of leukotriene B(4) showed significant differences of clinical interest. Among survivors we observed practically no gradient (-4.9%), whereas among nonsurvivors we found a substantial positive gradient of 41.6% for the elevated arterial (post-pulmonary) values, compared with the pulmonary-artery (pre-pulmonary) values, and this difference was statistically significant (p = 0.02). CONCLUSIONS: The pro-inflammatory eicosanoid leukotriene B(4) showed the best correlation with lung-injury severity and outcome in patients with ARDS.

Risk factors for intubation as a guide for noninvasive ventilation in patients with severe acute cardiogenic pulmonary edema.

OBJECTIVE: Noninvasive ventilation may reduce the endotracheal intubation rate in patients with acute cardiogenic pulmonary edema. However, criteria for selecting candidates for this technique are not well established. We analyzed a cohort of patients with severe acute cardiogenic pulmonary edema managed by conventional therapy to identify risk factors for intubation. These factors were used as guide for indications for noninvasive ventilation. DESIGN AND SETTING: Observational cohort registry in the ICU and emergency and cardiology departments in a community teaching hospital. PATIENTS: . 110 consecutive patients with acute cardiogenic pulmonary edema, 80 of whom received conventional oxygen therapy. INTERVENTIONS: Physiological measurements and blood gas samples registered upon admission. MEASUREMENTS AND RESULTS: Twenty-one patients (26%) treated with conventional oxygen therapy needed intubation. Acute myocardial infarction, pH below 7.25, low ejection fraction (<30%), hypercapnia, and systolic blood pressure below 140 mmHg were independent predictors for intubation. Conversely, systolic blood pressure of 180 mmHg or higher showed to be a protective factor since only two patients with this blood pressure value required intubation (8%)], both presenting with a pH lower than 7.25. Considering systolic blood pressure lower than 180 mmHg, patients who showed hypercapnia presented a high intubation rate (13/21, 62%) whereas the rate of intubation in patients with normocapnia was intermediate (6/23, 26%). All normocapnic patients with pH less than 7.25 required intubation. No patient with hypocapnia was intubated regardless the level of blood pressure. CONCLUSIONS: Patients with pH less than 7.25 or systolic blood pressure less than 180 mmHg associated with hypercapnia should be promptly considered for noninvasive ventilation. With this strategy about 40% of the patients would be initially treated with this technique, which would involve nearly 90% of the patients that require intubation.