Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non- SARS-CoV-2 community-acquired pneumonia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD. METHODS: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality. RESULTS: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death. CONCLUSION: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality.

Community-Acquired Pneumonia in Children: Rapid Evidence Review.

In the United States, pneumonia is the most common cause of hospitalization in children. Even in hospitalized children, community-acquired pneumonia is most likely of viral etiology, with respiratory syncytial virus being the most common pathogen, especially in children younger than two years. Typical presenting signs and symptoms include tachypnea, cough, fever, and anorexia. Findings most strongly associated with an infiltrate on chest radiography in children with clinically suspected pneumonia are grunting, history of fever, retractions, crackles, tachypnea, and the overall clinical impression. Chest radiography should be ordered if the diagnosis is uncertain, if patients have hypoxemia or significant respiratory distress, or if patients fail to show clinical improvement within 48 to 72 hours after initiation of antibiotic therapy. Outpatient management of community-acquired pneumonia is appropriate in patients without respiratory distress who can tolerate oral antibiotics. Amoxicillin is the first-line antibiotic with coverage for Streptococcus pneumoniae for school-aged children, and treatment should not exceed seven days. Patients requiring hospitalization and empiric parenteral therapy should be transitioned to oral antibiotics once they are clinically improving and able to tolerate oral intake. Childhood and maternal immunizations against S. pneumoniae, Haemophilus influenzae type b, Bordetella pertussis, and influenza virus are the key to prevention.

The prognostic value of serum albumin levels and respiratory rate for community-acquired pneumonia: A prospective, multi-center study.

Community-acquired pneumonia (CAP) is a respiratory disease frequently requiring hospital admission, and a significant cause of death worldwide. This study aimed to investigate the prognostic value of clinical indicators. A prospective, multi-center study was conducted (January 2017-December 2018) where patient demographic and clinical data were recorded (N = 366). The 30-day mortality rate was 5.46%. Cox Regression analyses showed that serum albumin (ALB) and respiratory rate (RR) were independent prognostic variables for 30-day survival in patients with CAP. Albumin negatively correlated with the Pneumonia Severity Index (PSI) and CURB-65 scores using Pearson and Spearman tests. Survival curves showed that a RR >24 breaths/min or ALB ≤30 g/L were associated with a significantly higher risk of mortality. The area-under-the-curve (AUC) for predicting 30-day mortality in patients with CAP was 0.762, 0.763, 0.790, and 0.784 for ALB, RR, PSI, and CURB-65, respectively. The AUC for the prediction of 30-day mortality using ALB combined with PSI, CURB-65 scores, and RR was 0.822 (95% CI 0.731-0.912), 0.847 (95% CI 0.755-0.938), and 0.847 (95% CI 0.738-0.955), respectively. Albumin and RR were found to be reliable prognostic factors for CAP. This combination showed equal predictive value when compared to adding ALB assessment to PSI and CURB-65 scores, which could improve their prognostic accuracy.

Lung volume reduction and infection localization revealed in Big data CT imaging of COVID-19.

The ongoing worldwide COVID-19 pandemic has become a huge threat to global public health. Using CT image, 3389 COVID-19 patients, 1593 community-acquired pneumonia (CAP) patients, and 1707 nonpneumonia subjects were included to explore the different patterns of lung and lung infection. We found that COVID-19 patients have a significant reduced lung volume with increased density and mass, and the infections tend to present as bilateral lower lobes. The findings provide imaging evidence to improve our understanding of COVID-19.

Airway invasion in non-neurologically ill patients with dysphagia: Contributing factors and associated problems during swallowing process. A retrospective observational study.

Dysphagia can occur among patients receiving medical care despite having no history of neurologic disease. The current study aimed to investigate factors contributing to airway invasion among non-neurologically ill patients with dysphagia.This retrospective study included 52 non-neurologically ill patients who complained of swallowing difficulty and consulted the Department of Rehabilitation Medicine for videofluoroscopic swallowing studies between January 2018 and June 2019. Patients were then divided into 2 groups according to the presence of airway invasion (penetration or aspiration) based on videofluoroscopic swallowing study findings, with group 1 (n = 26) consisting of patients with airway invasion and group 2 (n = 26) consisting of those without airway invasion. Demographic information, functional ambulation ability within the past 3 months, presence of community acquired pneumonia (CAP), nutritional status, degree of dehydration, history of intensive care unit stay, history of endotracheal intubation, and videofluoroscopic dysphagia scale were reviewed.Patients with airway invasion exhibited decreased functional ambulation ability, greater incidence of CAP, and lower serum albumin concentration than patients without airway invasion (P < .05). Airway invasion among non-neurologically ill patients was significantly associated with functional ambulation ability [odds ratio (OR), 3.57; 95% confidence interval (CI), 1.14-11.19; P = .03], serum albumin concentration under 3.5 g/dL (OR, 4.90; 95% CI, 1.39-17.32; P = .01), and presence of CAP (OR, 5.06; 95% CI, 1.56-16.44; P = .01). Groups 1 and 2 had a videofluoroscopic dysphagia scale score of 37.18 and 16.17, respectively (P < .05). Moreover, bolus formation, tongue-to-palate contact, premature bolus loss, vallecular residue, coating of pharyngeal wall, and aspiration score differed significantly between both groups (P < .05).Airway invasion among non-neurologically ill patients was related to decreased functional ambulation ability, lower serum albumin concentration, and presence of CAP. The results presented herein can help guide clinical management aimed at preventing airway invasion among non-neurologically ill patients.

Presence of urinary symptoms in bacteremic urinary tract infection: a retrospective cohort study of Escherichia coli bacteremia.

BACKGROUND: It is important to understand clinical features of bacteremic urinary tract infection (bUTI), because bUTI is a serious infection that requires prompt diagnosis and antibiotic therapy. Escherichia coli is the most common and important uropathogen. The objective of our study was to characterize the clinical presentation of E coli bUTI. METHODS: Retrospective cohort study of consecutive adult patients admitted for community acquired E. coli bacteremia from January 1, 2015 to December 31, 2016 was conducted at 4 acute care academic and community hospitals in Toronto, Ontario, Canada. Logistic regression models were developed to identify E coli bUTI cases without urinary symptoms. RESULTS: Of 462 patients with E. coli bacteremia, 284 (61.5%) patients had a urinary source. Of these 284 patients, 161 (56.7%) had urinary symptoms. In a multivariable model, bUTI without urinary symptoms were associated with older age (age < 65 years as reference, age 65-74 years had OR of 2.13 95% CI 0.99-4.59 p = 0.0523; age 75-84 years had OR of 1.80 95% CI 0.91-3.57 p = 0.0914; age > =85 years had OR of 2.95 95% CI 1.44-6.18 p = 0.0036) and delirium (OR of 2.12 95% CI 1.13-4.03 p = 0.0207). Sepsis by SIRS criteria was present in 274 (96.5%) of all bUTI cases and 119 (96.8%) of bUTI cases without urinary symptoms. CONCLUSION: The majority of patients with E. coli bacteremia had a urinary source. A significant proportion of bUTI cases had no urinary symptoms elicited on history. Elderly and delirious patients were more likely to have bUTI without urinary symptoms. In elderly and delirious patients with sepsis by SIRS criteria but without a clear infectious source, clinicians should suspect, investigate, and treat for bUTI.

Declined Functional Status Prolonged Hospital Stay for Community-Acquired Pneumonia in Seniors.

PURPOSE: Among senior community-acquired pneumonia (CAP) survivors, functional status after hospitalization is often decreased. This study investigated the change of functional status affecting delayed discharge. PATIENTS AND METHODS: This retrospective observational study was conducted in two medical facilities from January 2016 to December 2018. Hospitalized CAP patients >64 years old were divided into two groups: an early group discharged ≤1 week after ending antibiotic treatment and a delayed group discharged >1 week after ending antibiotic treatment. The primary outcome was decline in functional status. RESULTS: The early group comprised 170 patients and the delayed group comprised 155 patients (median age: 78 vs 82 years; p = 0.007). Distribution of the causative microorganisms and initial prescription of antibiotics showed no significant differences in the two groups (p=0.38; p=0.83, respectively) More patients showed decline in functional status in the delayed group than the early group (16 (9.4%) vs 49 (31.6%), p<0.001), even if rehabilitation was more frequently conducted (77 (45.3%) vs 118 (76.1%); p<0.001). Higher medical expenses were observed in the delayed group ($8631 vs $3817, respectively; p<0.001). Multivariable regression analysis of factors contributing delayed discharge revealed that decreased functional status, pneumonia severity index (PSI) categories, rehabilitation enrolled, aspiration and age were independently associated with delayed discharge (odds ratio 4.31, 95% confidence interval (CI) 2.32-7.98; 2.34, 95% CI 1.43-3.82; 15.96, 95% CI 4.56-55.82 (PSI V vs II); 2.48, 95% CI 1.11-5.98; and 1.03, 95% CI 1.01-1.06; respectively). CONCLUSION: Functional status decline was independently associated with extended hospitalization.

Fatal fulminant community-acquired pneumonia caused by hypervirulent Klebsiella pneumoniae K2-ST86: Case report.

RATIONALE: Invasive community-acquired infections, including pyogenic liver abscesses, caused by hypervirulent Klebsiella pneumoniae (hvKp) strains have been well recognized worldwide. Among these, sporadic hvKp-related community-acquired pneumonia (CAP) is an acute-onset, rapidly progressing disease that can likely turn fatal, if left untreated. However, the clinical diagnosis of hvKp infection remains challenging due to its non-specific symptoms, lack of awareness regarding this disease, and no consensus definition of hvKp. PATIENT CONCERNS: A 39-year-old man presented with high-grade fever and sudden-onset chest pain. Laboratory testing revealed an elevated white blood cell count of 11,600 cells/µl and C-reactive protein level (>32 mg/dl). A chest X-ray and computed tomography revealed a focal consolidation in the left lower lung field. DIAGNOSIS: Diagnosis of fulminant CAP caused by a hvKp K2-ST86 strain was made based upon multilocus sequencing typing (MLST). INTERVENTIONS: The patient was treated with ampicillin/sulbactam. OUTCOMES: The pneumonia became fulminant. Despite intensive care and treatment, he eventually died 15.5 hours after admission. LESSONS: This is the first case of fatal fulminant CAP caused by a hvKp K2-ST86 strain reported in Japan. MLST was extremely useful for providing a definitive diagnosis for this infection. Thus, we propose that a biomarker-based approach should be considered even for an exploratory diagnosis of CAP related to hvKp infection.

Clinical validation of expert consensus statements for respiratory physiotherapy management of invasively ventilated adults with community-acquired pneumonia: A qualitative study.

OBJECTIVES: To conduct multidisciplinary peer-review of expert consensus statements for respiratory physiotherapy for invasively ventilated adults with community-acquired pneumonia, to determine clinical acceptability for development into a clinical practice guideline. RESEARCH METHODOLOGY: A qualitative study was undertaken using focus groups (n = 3) conducted with clinician representatives from five Australian states. Participants were senior intensive care physiotherapists, nurses and consultants. Thematic analysis was used, with a deductive approach to confirm clinical validity, and inductive analysis to identify new themes relevant to the application of the 38 statements into practice. SETTING: Adult intensive care. FINDINGS: Senior intensive care clinicians from physiotherapy (n = 16), medicine (n = 6) and nursing (n = 4) participated. All concurred that the consensus statements added valuable guidance to practice; twenty-nine (76%) were deemed relevant and applicable for the intensive care setting without amendment, with modifications suggested for remaining nine statements to enhance utility. Overarching themes of patient safety, teamwork and communication and culture were identified as factors influencing clinical application. Cultural differences in practice, particularly related to patient positioning, was evident between jurisdictions. Participants raised practicality and safety concerns for two statements related to the use of head-down patient positioning. CONCLUSION: Multidisciplinary peer-review established clinical validity of expert consensus statements for implementation with invasively ventilated adults with community-acquired pneumonia.

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

Serum Prealbumin Improves the Sensitivity of Pneumonia Severity Index in Predicting 30-day Mortality of CAP Patients.

BACKGROUND: Serum prealbumin (PAB) is an effective tool to evaluate patients with malnutrition. In recent years, studies have shown that PAB is statistically reduced during the course of disease infection. The pneumonia severity index (PSI) scoring system is one of the most widely used scoring tools to evaluate the condition and prognosis of community acquired pneumonia (CAP) patients. However, few studies have reported on PSI combined with blood indicators to predict the prognosis of pneumonia. The aim of this study was to investigate the prognostic value of PAB combined with PSI in patients with CAP. METHODS: We retrospectively analyzed the data of 400 patients who met the inclusion criteria. Death and survival were selected as prognostic indicators of pneumonia. On the first day after admission, venous blood samples were taken to test PAB and PSI scores. Subject operating characteristic curve (ROC) was used to evaluate PSI, PAB, and PSI combined with PAB to predict 30-day mortality of CAP patients. RESULTS: The 30-day mortality rate of CAP patients was 10.5% (42/400). PAB and PSI score were independent risk factors for 30-day mortality in CAP patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PAB predicting the death of CAP patients were 86.3%, 79%, 50.74%, and 95.83%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSI predicting the death of CAP patients were 74.80%, 63%, 33.71%, and 90.99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the combined index predicting the death of CAP patients were 95.20%, 77.80%, 51.70% and 98.41%, respectively. CONCLUSIONS: Serum prealbumin is a relatively simple acquired index and an independent risk factor for death in CAP patients. Serum prealbumin improves the sensitivity of pneumonia severity index in predicting 30-day mortality of CAP patients.

Confusion, respiratory rate, shock index (CRSI-65) score in the emergency department triage may be a new severity scoring method for community-acquired pneumonia.

OBJECTIVES: To investigate whether confusion, respiratory rate, shock index-age ≥65 years (CRSI-65) score, consisting of basic physiological parameters, can be used for severity prediction in patients with community-acquired pneumonia. METHODS: This is a prospective cohort and single-center study conducted in Bolu Abant Izzet Baysal University Hospital, Bolu, Turkey between January 2018 and June 2018. The study investigated CRSI-65 score in predicting 4-week mortality and the need for intensive care for patients with community-acquired pneumonia. RESULTS: A total of 58 patients with community-acquired pneumonia admitted to the emergency department were included in this study. Of the patients, 62.1% were males (n=36), and the mean age of the patients was 72.87 ± 12.30 years. After 4 weeks of follow-up, CURB-65 and CRSI-65 scores showed similar results in predicting mortality with respect to specificity, sensitivity, and positive and negative predictive values. Area under the receiver operating characteristic curve was 0.926 for the CURB-65 (95% confidence interval [CI] 0.853-0.999) and 0.954 for the CRSI-65 (95% CI 0.899-0.999). CONCLUSION: Similar to the CURB-65 score, the CRSI-65 score appears to be useful in predicting 4-week mortality. The evaluation of CRSI-65 score can be used in emergency department triage, primary care, and non-hospital settings.

Community-acquired pneumonia in critically ill very old patients: a growing problem.

Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit.

Nasopharyngeal Carriage of Invasive Pneumococcal Serotypes During Childhood Community-Acquired Alveolar Pneumonia Is Associated With Specific Clinical Presentation.

BACKGROUND: Streptococcus pneumoniae (Pnc) serotypes differ in invasive potential. We examined whether community-acquired alveolar pneumonia (CAAP) in children carrying commonly recognized pneumonia invasive pneumococcal serotypes ([PnIST] 1, 5, 7F, 14, and 19A) differs from CAAP in children carrying less invasive serotypes (non-PnIST) or no Pnc (Pnc-neg). METHODS: Children <5 years, visiting the only regional Pediatric Emergency Room, with radiologically proven CAAP were enrolled. Nasopharyngeal cultures were processed for pneumococcal isolation and serotyping. Clinical and demographic characteristics were recorded. The study was conducted before pneumococcal conjugate vaccine implementation in Israel. RESULTS: A total of 1423 CAAP episodes were recorded: PnIST, 300 (21.1%); non-PnIST, 591 (41.5%); and Pnc-neg, 532 (37.4%). After adjustment for age, ethnicity, seasonality, and previous antibiotics, the following variables were positively associated with PnIST carriage compared with both groups: temperature ≥39°C, peripheral white blood cell count ≥20 000/mm3, C-reactive protein ≥70.0 mg/L, and serum sodium <135 mEq/L. Lower oxygen saturation, viral detection, and comorbidities were negatively associated with Pn-IST carriage (odds ratios, <1.0). Differences between non-PnIST carriers and Pnc-neg groups were smaller or nonsignificant. CONCLUSIONS: Young children with CAAP carrying common PnIST had a lower proportion of comorbidities, hypoxemia, and viral detection and had more intense systemic inflammatory response than those carrying non-PnIST or not carrying Pnc.

Effect of corticosteroids on myocardial injury among patients hospitalized for community-acquired pneumonia: rationale and study design. The colosseum trial.

Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury that can be isolated or associated with myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers the incidence of MI during the hospital stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. The primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 days from hospital admission and during 2 years' follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After discharge, all patients will be followed-up 2 years. This is the first clinical trial aimed at examining whether methylprednisolone treatment may reduce myocardial injury. The results of this trial may constitute the basis for conducting a larger multicenter trial aimed to evaluate the effect of corticosteroid on cardiovascular events in this setting.

Risk factors and clinical characteristics of patients with nosocomial influenza A infection.

Influenza is a public health burden, responsible for more than half a million deaths worldwide each year and explosive outbreaks in-hospital care units. At present, little is known about clinical characteristics and outcomes with nosocomial influenza infection. To assess clinical characteristics and outcome between nosocomial and community-acquired (CA) influenza in a tertiary care hospital. A retrospective study of hospitalized patients in a French tertiary care hospital from 1st December 2016 to 28th February 2017 for flu-illness confirmed by reverse transcription PCR. Overall, 208 patients with laboratory-confirmed influenza were included; whose 49 nosocomial cases (23.6%). Patients with nosocomial influenza were significantly older (79.1 ± 15.5 vs 64.8 ± 31.1 years old; P = .003), with the more rapidly fatal disease (10.2% vs 1.3%; P = .0032). They had a less respiratory failure (8.2% vs 21.4%; P = .036) but had a longer length of hospitalization (47.3 vs 12.9 days; P < .001) than patients with CA influenza. During this influenza outbreak, 19 patients died (9.1%), none of them were vaccinated. Effective control of outbreaks in hospital facilities is challenging. Hospitalized patients are vulnerable to nosocomial Influenza infections that can increase the length of stay and be responsible for the death. Surveillance and early warning systems should be encouraged. Vaccination policies in conjunction with isolation measures and better hand hygiene could reduce virus spreading in hospitals.

Neutrophils in community-acquired pneumonia: parallels in dysfunction at the extremes of age.

"Science means constantly walking a tight rope" Heinrich Rohrer, physicist, 1933. Community-acquired pneumonia (CAP) is the leading cause of death from infectious disease worldwide and disproportionately affects older adults and children. In high-income countries, pneumonia is one of the most common reasons for hospitalisation and (when recurrent) is associated with a risk of developing chronic pulmonary conditions in adulthood. Pneumococcal pneumonia is particularly prevalent in older adults, and here, pneumonia is still associated with significant mortality despite the widespread use of pneumococcal vaccination in middleand high-income countries and a low prevalence of resistant organisms. In older adults, 11% of pneumonia survivors are readmitted within months of discharge, often with a further pneumonia episode and with worse outcomes. In children, recurrent pneumonia occurs in approximately 10% of survivors and therefore is a significant cause of healthcare use. Current antibiotic trials focus on short-term outcomes and increasingly shorter courses of antibiotic therapy. However, the high requirement for further treatment for recurrent pneumonia questions the effectiveness of current strategies, and there is increasing global concern about our reliance on antibiotics to treat infections. Novel therapeutic targets and approaches are needed to improve outcomes. Neutrophils are the most abundant immune cell and among the first responders to infection. Appropriate neutrophil responses are crucial to host defence, as evidenced by the poor outcomes seen in neutropenia. Neutrophils from older adults appear to be dysfunctional, displaying a reduced ability to target infected or inflamed tissue, poor phagocytic responses and a reduced capacity to release neutrophil extracellular traps (NETs); this occurs in health, but responses are further diminished during infection and particularly during sepsis, where a reduced response to granulocyte colony-stimulating factor (G-CSF) inhibits the release of immature neutrophils from the bone marrow. Of note, neutrophil responses are similar in preterm infants. Here, the storage pool is decreased, neutrophils are less able to degranulate, have a reduced migratory capacity and are less able to release NETs. Less is known about neutrophil function from older children, but theoretically, impaired functions might increase susceptibility to infections. Targeting these blunted responses may offer a new paradigm for treating CAP, but modifying neutrophil behaviour is challenging; reducing their numbers or inhibiting their function is associated with poor clinical outcomes from infection. Uncontrolled activation and degranulation can cause significant host tissue damage. Any neutrophil-based intervention must walk the tightrope described by Heinrich Rohrer, facilitating necessary phagocytic functions while preventing bystander host damage, and this is a significant challenge which this review will explore.

High expression of miR-222-3p in children with Mycoplasma pneumoniae pneumonia.

OBJECTIVES: Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children. However, its mechanism of pathogenesis is not fully understood, and microRNAs might play a role. This study aimed to explore the microRNA-222-3p (miR-222-3p) expression and its possible role in children with M.pneumoniae pneumonia (MPP). METHODS: Thirty-six children with MPP and twenty-seven age-matched controls from Children's Hospital of Soochow University were enrolled in this study. MiR-222-3p and cluster of differentiation 4 (CD4) mRNA were detected using real-time PCR in children's peripheral blood plasma samples. THP-1 cells and mice were stimulated with M.pneumoniae lipid-associated membrane proteins(LAMPs). RESULTS: Children with MPP had significantly higher levels of miR-222-3p and lower levels of CD4 in peripheral blood plasma (P <  0.05). Additionally, Sixteen children with MPP complicated with pleural effusion had higher miR-222-3p levels than those without pleural effusion. MiR-222-3p or CD4 in THP-1 cells increased or decreased, respectively, in a dose dependent manner after LAMP stimulation. In LAMP-stimulated mice massive inflammatory cells infiltrates surrounded the bronchioles, and miR-222-3p increased in the bronchoalveolar lavage fluid. In conclusion, miR-222-3p was highly expressed in children with MPP, especially those with pleural effusion. CONCLUSION: Small sample studies showed that M.pneumoniae or its LAMPs could increase miR-222-3p and decrease CD4 in macrophages,both in vitro and vivo.Thus, miR-222-3p might be an MPP biomarker for the diagnosis and prognosis.

Chronic alcohol abuse affects the clinical course and outcome of community-acquired bacterial meningitis.

The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (p < 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (p = 0.002) and lower on the Glasgow Coma Scale (GCS) (p < 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (p < 0.001). Furthermore, alcoholics were less likely to complain of headache (p < 0.001) and nausea/vomiting (p = 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (p = 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (p = 0.036), presence of seizures (p = 0.041), male gender (p = 0.042), and absence of nausea/vomiting (p = 0.040). Furthermore, alcoholism (p = 0.031), lower GCS score (p = 0.001), and higher blood urea concentration (p = 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.