Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Stenotrophomonas maltophilia pneumonia in critical COVID-19 patients.

Stenotrophomonas maltophilia, an environmental aerobic non-fermentative Gram-negative bacilli, has gained attention in many nosocomial outbreaks. COVID-19 patients in intensive care unit have extended hospital stay and are severely immunosuppressed. This study aimed to determine the prevalence and risk factors of S. maltophilia pneumonia in critical COVID-19 patients. A total of 123 COVID-19 patients in ICU admitted between March 2020 and March 2021 were identified from the authors' institutional database and assessed for nosocomial pneumonia. Demographic data and factors predisposing to S. maltophilia pneumonia were collected and analyzed. The mean age was 66 ± 13 years and 74% were males. Median APACHE and SOFA scores were 13 (IQR = 8-19) and 4 (3-6), respectively. The Median NEWS2 score was 6 (Q1 = 5; Q3 = 8). The Median ICU stay was 12 (Q1 = 7; Q3 = 22) days. S. maltophilia was found in 16.3% of pneumonia patients, leading to a lengthier hospital stay (34 vs. 20 days; p < 0.001). Risk factors for S. maltophilia pneumonia included previous treatment with meropenem (p < 0.01), thrombopenia (p = 0.034), endotracheal intubation (p < 0.001), foley catheter (p = 0.009) and central venous catheter insertion (p = 0.016). S. maltophilia nosocomial pneumonia is frequent in critical COVID-19 patients. Many significant risk factors should be addressed to reduce its prevalence and negative impact on outcomes.

Assessment of the pneumonia severity score in community-acquired and nursing and healthcare-associated pneumonia due to COVID-19.

INTRODUCTION: The Japanese Respiratory Society (JRS) pneumonia guidelines recommend simple predictive rules, the A-DROP scoring system, for assessment of the severity of community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP). We evaluated whether the A-DROP system can be adapted for assessment of the severity of coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Data from 1141 patients with COVID-19 pneumonia were analyzed, comprising 502 patients observed in the 1st to 3rd wave period, 338 patients in the 4th wave and 301 patients in the 5th wave in Japan. RESULTS: The mortality rate and mechanical ventilation rate were 0% and 1.4% in patients classified with mild disease (A-DROP score, 0 point), 3.2% and 46.7% in those with moderate disease (1 or 2 points), 20.8% and 78.3% with severe disease (3 points), and 55.0% and 100% with extremely severe disease (4 or 5 points), indicating an increase in the mortality and mechanical ventilation rates in accordance with severity (Cochran-Armitage trend test; p = <0.001). This significant relationship between the severity in the A-DROP scoring system and either the mortality rate or mechanical ventilation rate was observed in patients with COVID-19 CAP and NHCAP. In each of the five COVID-19 waves, the same significant relationship was observed. CONCLUSIONS: The mortality rate and mechanical ventilation rate in patients with COVID-19 pneumonia increased depending on severity classified according to the A-DROP scoring system. Our results suggest that the A-DROP scoring system can be adapted for the assessment of severity of COVID-19 CAP and NHCAP.

Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update.

The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Impact of nutrition and physical activity on outcomes of hospital-acquired pneumonia.

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.

Updates in the management of respiratory virus infections in ICU patients: revisiting the non-SARS-CoV-2 pathogens.

INTRODUCTION: Although viruses are an underestimated cause of community-acquired pneumonias (CAP) and hospital-acquired pneumonias (HAP)/ventilator-associated pneumonias (VAP) in intensive care unit (ICU) patients, they have an impact on morbidity and mortality. AREAS COVERED: In this perspective article, we discuss the available data regarding the management of severe influenza CAP and herpesviridae HAP/VAP. We review diagnostic and therapeutic strategies in order to give clear messages and address unsolved questions. EXPERT OPINION: Influenza CAP affects yearly thousands of people; however, robust data regarding antiviral treatment in the most critical forms are scarce. While efficacy of oseltamivir has been investigated in randomized controlled trials (RCT) in uncomplicated influenza, only observational data are available in ICU patients. Herpesviridae are an underestimated cause of HAP/VAP in ICU patients. Whilst incidence of herpesviridae identification in samples from lower respiratory tract of ICU patients is relatively high (from 20% to 50%), efforts should be made to differentiate local reactivation from true lung infection. Only few randomized controlled trials evaluated the efficacy of antiviral treatment in herpesviridae reactivation/infection in ICU patients and all were exploratory or negative. Further studies are needed to evaluate the impact of such treatment in specific populations.

Clinical features of nursing and healthcare-associated pneumonia due to COVID-19.

INTRODUCTION: The objective of this study was to clarify the clinical differences between nursing and healthcare-associated pneumonia (NHCAP) and community-acquired pneumonia (CAP) due to COVID-19. We also investigated the clinical characteristics to determine whether there is a difference between the variant and non-variant strain in patients with NHCAP due to COVID-19. In addition, we analyzed the clinical outcomes in NHCAP patients with mental disorders who were hospitalized in a medical institution for treatment of mental illness. METHODS: This study was conducted at five institutions and assessed a total of 836 patients with COVID-19 pneumonia (154 cases were classified as NHCAP and 335 had lineage B.1.1.7.). RESULTS: No differences in patient background, clinical findings, disease severity, or outcomes were observed in patients with NHCAP between the non-B.1.1.7 group and B.1.1.7 group. The median age, frequency of comorbid illness, rates of intensive care unit stay, and mortality rate were significantly higher in patients with NHCAP than in those with CAP. Among the patients with NHCAP, the mortality rate was highest at 37.5% in patients with recent cancer treatment, followed by elderly or disabled patients receiving nursing care (24.3%), residents of care facilities (23.0%), patients receiving dialysis (13.6%), and patients in mental hospitals (9.4%). CONCLUSIONS: Our results demonstrated that there were many differences in the clinical characteristics between NHCAP patients and CAP patients due to COVID-19. It is necessary to consider the prevention and treatment content depending on the presence or absence of applicable criteria for NHCAP.

Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.

Non-ventilator associated hospital acquired pneumonia incidence and health outcomes among U.S. veterans from 2016-2020.

Among 1,635,711 Veteran acute care admissions (FY2016-2020), the risk of non-ventilator associated hospital acquired pneumonia (NV-HAP) was 1.26 cases per 1,000 hospitalized days and decreased linearly over time with an uptick in cases in the last year coinciding with the onset of the covid-19 pandemic. Veterans who develop NV-HAP experience remarkably higher 30-day and 1-year mortality, longer length of stay, and higher rates of inpatient sepsis. Monitoring and prevention measures may substantially reduce negative outcomes.

The clinical role of host and bacterial-derived extracellular vesicles in pneumonia.

Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.

Risk factors for bacterial infections in patients with moderate to severe COVID-19: A case-control study.

Adverse outcomes in coronavirus infection disease-19 (COVID-19) patients are not always due to the direct effects of the viral infection, but often due to bacterial coinfection. However, the risk factors for such bacterial coinfection are hitherto unknown. A case-control study was conducted to determine risk factors for bacterial infection in moderate to critical COVID-19. Out of a total of 50 cases and 50 controls, the proportion of cases with severe/critical disease at presentation was 80% in cases compared to 30% in controls (p < 0.001). The predominant site was hospital-acquired pneumonia (72%) and the majority were Gram-negative organisms (82%). The overall mortality was 30%, with comparatively higher mortality among cases (42% vs. 18%; p = 0.009). There was no difference between procalcitonin levels in both groups (p = 0.883). In multivariable logistic regression analysis, significant independent association was found with severe/critical COVID-19 at presentation (AOR: 4.42 times; 95% CI: 1.63-11.9) and use of steroids (AOR: 4.60; 95% CI: 1.24-17.05). Notably, 64% of controls were administered antibiotics despite the absence of bacterial coinfection or secondary infection. Risk factors for bacterial infections in moderate to critically ill patients with COVID-19 include critical illness at presentation and use of steroids. There is widespread empiric antibiotic utilization in those without bacterial infection.

A severe case of human coronavirus 229E pneumonia in an elderly man with diabetes mellitus: a case report.

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.

Extra-pulmonary complications of 45 critically ill patients with COVID-19 in Yichang, Hubei province, China: A single-centered, retrospective, observation study.

ABSTRACT: Mortality of critically ill patients with coronavirus disease 2019 (COVID-19) was high. Aims to examine whether time from symptoms onset to intensive care unit (ICU) admission affects incidence of extra-pulmonary complications and prognosis in order to provide a new insight for reducing the mortality. A single-centered, retrospective, observational study investigated 45 critically ill patients with COVID-19 hospitalized in ICU of The Third People's Hospital of Yichang from January 17 to March 29, 2020. Patients were divided into 2 groups according to time from symptoms onset to ICU admission (>7 and ≤7 days) and into 2 groups according to prognosis (survivors and non-survivors). Epidemiological, clinical, laboratory, radiological characteristics and treatment data were studied. Compared with patients who admitted to the ICU since symptoms onset ≤7 days (55.6%), patients who admitted to the ICU since symptoms onset >7 days (44.4%) were more likely to have extra-pulmonary complications (19 [95.0%] vs 16 [64.0%], P = .034), including acute kidney injury, cardiac injury, acute heart failure, liver dysfunction, gastrointestinal hemorrhage, hyperamylasemia, and hypernatremia. The incidence rates of acute respiratory distress syndrome, pneumothorax, and hospital-acquired pneumonia had no difference between the 2 groups. Except activated partial thromboplastin and Na+ concentration, the laboratory findings were worse in group of time from symptoms onset to ICU admission >7 days. There was no difference in mortality between the 2 groups. Of the 45 cases in the ICU, 19 (42.2%) were non-survivors, and 16 (35.6%) were with hospital-acquired pneumonia. Among these non-survivors, hospital-acquired pneumonia was up to 12 (63.2%) besides higher incidence of extra-pulmonary complications. However, hospital-acquired pneumonia occurred in only 4 (15.4%) survivors. Critically ill patients with COVID-19 who admitted to ICU at once might get benefit from intensive care via lower rate of extra-pulmonary complications.

SARS-CoV-2-related pneumonia cases in pneumonia picture in Russia in March-May 2020: Secondary bacterial pneumonia and viral co-infections.

BACKGROUND: We are communicating the results of investigating statistics on SARS-CoV-2-related pneumonias in Russia: percentage, mortality, cases with other viral agents, cases accompanied by secondary bacterial pneumonias, age breakdown, clinical course and outcome. METHODS: We studied two sampling sets (Set 1 and Set 2). Set 1 consisted of results of testing 3382 assays of out-patients and hospital patients (5-88 years old) with community-acquired and hospital-acquired pneumonia of yet undetermined aetiology. Set 2 contained results of 1204 assays of hospital patients (12-94 years old) with pneumonia and COVID-19 already diagnosed by molecular biological techniques in test laboratories. The results were collected in twelve Russian cities/provinces in time range 2 March - 5 May 2020. Assays were analysed for 10 bacterial, 15 viral, 2 fungal and 2 parasitic aetiological agents. RESULTS: In Set 1, 4.35% of total pneumonia cases were related to SARS-CoV-2, with substantially larger proportion (18.75%) of deaths of pneumonia with COVID-19 diagnosed. However, studying Set 2, we revealed that 52.82% patients in it were also positive for different typical and atypical aetiological agents usually causing pneumonia. 433 COVID-19 patients (35.96%) were tested positive for various bacterial aetiological agents, with Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae infections accounting for the majority of secondary pneumonia cases. CONCLUSIONS: SARS-CoV-2, a low-pathogenic virus itself, becomes exceptionally dangerous if secondary bacterial pneumonia attacks a COVID-19 patient as a complication. An essential part of the severest complications and mortality associated with COVID-19 in Russia in March-May 2020, may be attributed to secondary bacterial pneumonia and to a much less extent viral co-infections. The problem of hospital-acquired bacterial infection is exceptionally urgent in treating SARS-CoV-2 patients. The risk of secondary bacterial pneumonia and its further complications, should be given very serious attention in combating SARS-CoV-2.

High-dose methylprednisolone in nonintubated patients with severe COVID-19 pneumonia.

BACKGROUND: Recent trials with dexamethasone and hydrocortisone have demonstrated benefit in patients with coronavirus disease 2019 (COVID-19). Data on methylprednisolone are limited. METHODS: Retrospective cohort of consecutive adults with severe COVID-19 pneumonia on high-flow oxygen (FiO2  ≥ 50%) admitted to an academic centre in New York, from 1 March to 15 April 2020. We used inverse probability of treatment weights to estimate the effect of methylprednisolone on clinical outcomes and intensive care resource utilization. RESULTS: Of 447 patients, 153 (34.2%) received methylprednisolone and 294 (65.8%) received no corticosteroids. At 28 days, 102 patients (22.8%) had died and 115 (25.7%) received mechanical ventilation. In weighted analyses, risk for death or mechanical ventilation was 37% lower with methylprednisolone (hazard ratio 0.63; 95% CI 0.47-0.86; P = .003), driven by less frequent mechanical ventilation (subhazard ratio 0.56; 95% CI 0.40-0.79; P = .001); mortality did not differ between groups. The methylprednisolone group had 2.8 more ventilator-free days (95% CI 0.5-5.1; P = .017) and 2.6 more intensive care-free days (95% CI 0.2-4.9; P = .033) during the first 28 days. Complication rates were not higher with methylprednisolone. CONCLUSIONS: In nonintubated patients with severe COVID-19 pneumonia, methylprednisolone was associated with reduced need for mechanical ventilation and less-intensive care resource utilization without excess complications.

Polymerase-chain reaction testing to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection in Shinjuku, an epicenter in Tokyo: The Tokyo Women's Medical University model.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95-3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002-0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82-7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49-3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Prolonged treatment of COVID-19 pneumonia with high-flow nasal oxygen: A story of oxygen and resilience.

The COVID-19 pandemic has placed significant strain on the oxygen delivery infrastructure of health facilities in resource-constrained health systems. In this case report, we describe a patient with severe COVID-19 pneumonia who was managed with high-flow nasal oxygen for 40 days, with an eventual successful outcome. We discuss the oxygen delivery infrastructure needed to offer this intervention, as well as the psychosocial impact on those undergoing treatment.

Hospital-acquired SARS-CoV-2 pneumonia in a person living with HIV.

We report the case of a 38 year-old man living with well-controlled HIV on antiretroviral therapy who developed cerebellar symptoms and was admitted to hospital for management of an intraventricular cryptococcoma. During his hospital stay he contracted SARS CoV-2 infection within the hospital setting with a fatal outcome.

Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure.

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.