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Abstract Background Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum β-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department. Methods We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected. Results Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing. Conclusions K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

Staphylococcus aureus is commonly isolated in cystic fibrosis (CF) patients and is a primary cause of recurrent acute pulmonary infection and progressive decline in lung function (Akil and Muhlebach, 2018). Many CF patients are infected or colonized by a predominant S. aureus clone, which adapts to this hostile niche through various mechanisms, including genome rearrangements, emergence of small colony variants, mucoid phenotypes, and inactivity of the important virulence regulator agr (Schwerdt et al., 2018).

Abstract Background Parvimonas micra (P. micra) is a gram-positive anaerobic coccus that is detected widely on the skin, in the oral mucosa and in the gastrointestinal tract. In certain circumstances, P. micra can cause abdominal abscesses, bacteraemia and other infections. To the best of our knowledge, there have been no case reports describing the biological characteristics of P. micra-related pneumonia. These bacteria do not always multiply in an aerobic organ, such as the lung, and they could be easily overlooked because of the clinical mindset. Case presentation A 35-year-old pregnant woman was admitted to the emergency department 4 weeks prior to her due date who was exhibiting 5 points on the Glasgow coma scale. A computed tomography (CT) scan showed a massive haemorrhage in her left basal ganglia. She underwent a caesarean section and brain surgery before being admitted to the ICU. She soon developed severe pneumonia and hypoxemia. Given that multiple sputum cultures were negative, the patient’s bronchoalveolar lavage fluid was submitted for next-generation sequencing (NGS) to determine the pathogen responsible for the pneumonia; as a result, P. micra was determined to be the causative pathogen. Accordingly the antibiotic therapy was altered and the pneumonia improved. Conclusion In this case, we demonstrated severe pneumonia caused by the anaerobic organism P. micra, and the patient benefited from receiving the correct antibiotic. NGS was used as a method of quick diagnosis when sputum culture failed to distinguish the pathogen.

by Asefa Adimasu Taddese, Zelalem Nigussie Azene, Mehari Woldemariam Merid, Atalay Goshu Muluneh, Demiss Mulatu Geberu, Getahun Molla Kassa, Melaku Kindie Yenit, Sewbesew Yitayih Tilahun, Kassahun Alemu Gelaye, Habtamu Sewunet Mekonnen, Abere Woretaw Azagew, Chalachew Adugna Wubneh, Getaneh Mulualem Belay, Nega Tezera Assimamaw, Chilot Desta Agegnehu, Telake Azale, Animut Tagele Tamiru, Bayew Kelkay Rade, Eden Bishaw Taye, Zewudu Andualem, Henok Dagne, Kiros Terefe Gashaye, Gebisa Guyasa Kabito, Tesfaye Hambisa Mekonnen, Sintayehu Daba, Jember Azanaw, Tsegaye Adane, Mekuriaw Alemayehu Background COVID-19 is the novel coronavirus responsible for the ongoing global outbreak of acute respiratory disease and viral pneumonia. In order to tackle the devastating condition of the virus, countries need to attack the virus with aggressive and targeted tactics. Thus, to strengthen the COVID-19 mitigation measures and to give rapid response, there is an urgent need to understand the public’s knowledge and attitude about of the pandemic at this critical moment. Objective This study was aimed to assess the knowledge and attitude of communities about COVID-19 and associated factors among Gondar City residents. Methods A community based cross-sectional study was done among 623 respondents in Gondar city from April 20-27/2020. Data were collected using a structured questionnaire adapted from different literatures. The data were entered using Epi data version 3.1 and then exported into STATA version 14 for analysis. Bi-variable and multivariable binary logistic regression were performed. Adjusted odds ratio with 95% CI was used to declare statistically significant variables on the basis of p value less than 0.05 in the multivariable binary logistic regression model. Results The overall knowledge and attitude of the community towards COVID19 was 51.85% [95% CI (47.91%-55.78%)] and 53.13% [95% CI (49.20, 57.06%)], respectively. In this study, being married [AOR = 0.60 at 95% CI: (0.42, 0.86)], educational level; primary [AOR = 3.14 at 95% CI: (1.78,5.54)], secondary [AOR = 2.81 at 95% CI: (1.70,4.63)], college and above [AOR = 4.49 at 95% CI: 7.92, 13.98)], and family size [AOR = 1.80, at 95% CI: (1.05, 3.08)] were emerged as statistically significant factors impacting the knowledge of the community about COVID-19. Besides, educational level; primary [AOR = 1.76 at 95% CI: (1.03, 3.01)], secondary [AOR = 1.69 at 95% CI: (1.07, 2.68)], and college & above [AOR = 2.38 at 95% CI: (1.50, 3.79)], and family size; four to six members [AOR = 1.84 at 95% CI (1.27, 2.67)], above seven members [AOR = 1.79 at 95% CI (1.08, 2.96)] were factors identified as significantly attribute for positive attitude of the communities towards COVID-19. Conclusion More than half of the respondents had better knowledge and attitude regarding COVID-19. Higher educational level and larger family size were significant factors predominantly affecting the knowledge and attitude of the communities towards COVID-19.

A 66-year-old man attended our hospital with increasing shortness of breath, asthenia, and fever.

by John Njuma Libwea, Mark A. Fletcher, Paul Koki Ndombo, Angeline Boula, Nadesh Taku Ashukem, Madeleine Ngo Baleba, Rachel Sandrine Kingue Bebey, Eric Gaston Nkolo Mviena, Jean Tageube, Marie Kobela Mbollo, Sinata Koulla-Shiro, Shabir Madhi, Berthe-Marie Njanpop-Lafourcade, Ali Mohammad, Elizabeth Begier, Joanna Southern, Rohini Beavon, Bradford Gessner Background The 13-valent pneumococcal conjugate vaccine (PCV13) entered Cameroon’s childhood national immunization programme (NIP) in July 2011 under a 3-dose schedule (6, 10, 14 weeks of age) without any catch-up. We described the impact of PCV13 onserotype distribution among pneumococcal meningitis cases over time. Methods We used laboratory-based sentinel surveillance data to identify meningitis cases among 2- to 59-month-old children with clinically-suspected bacterial meningitis (CSBM) admitted to hospitals in Yaoundé (August 2011-December 2018). Purulent meningitis cases had a cerebrospinal fluid (CSF) white blood cell (WBC) count ≥20 per mm3. Pneumococcal meningitis cases had S. pneumoniae identified from CSF, with serotyping by polymerase chain reaction. Years 2011-2014 were described as early PCV13 era (EPE) and years 2015-2018 as late PCV13 era (LPE) impact periods. Results Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p = 0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0% (31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%). Conclusion Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F; nevertheless, PCV13 VSTs remain common. Because the analyzed surveillance system was not consistent or population based, we could not estimate incidence or overall impact; this emphasizes the need for improved surveillance to document further the utility of PCV13 immunization in Cameroon.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1037-1041, April 15, 2021.

Abstract Background The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. Materials and methods Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. Results Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759, p = 0.039). Conclusions In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

Abstract Background Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. Results We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. Conclusions Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. Trial registration Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.

Journal of Medical Virology, Accepted Article.

This cohort study characterizes the accuracy of the Sequential Organ Failure Assessment (SOFA) score to discriminate death from survival in patients with COVID-19 pneumonia receiving oxygen therapy for 4 hours or longer before undergoing endotracheal intubation.

Hypermucoviscous Klebsiella pneumoniae is an emerging cause of community-acquired liver abscess in Asian populations worldwide, affecting predominantly diabetic individuals with a normal biliary system and occasionally resulting in metastatic spread of infection (Siu et al., 2012). Virulence is partly due to the hypermucoviscous phenotype which is mediated by the K1 and K2 capsule serotype. In Singapore, Klebsiella liver abscess (KLA) has become the most common cause of liver abscess (Chan et al., 2013).

Objectives: Extracorporeal membrane oxygenation is a lifesaving therapy for patients with severe acute respiratory distress syndrome refractory to conventional mechanical ventilation. It is frequently complicated by both thrombosis and hemorrhage. A markedly prothrombotic state associated with high rates of venous thromboembolism has been described in patients with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) infection. These rates have currently not been described during extracorporeal membrane oxygenation in comparison to other viral pneumonias. Design: Retrospective observational study. Setting: Single high-volume tertiary critical care department at a university hospital. Patients: Patients 16 years old or greater receiving venovenous extracorporeal membrane oxygenation between March 1, 2020, and May 31, 2020, with coronavirus disease 2019 were compared with a cohort of patients with influenza pneumonia between June 1, 2012, and May 31, 2020. Interventions: None. Measurements and Main Results: The rates of venous thromboembolism and hemorrhage were compared in patients with coronavirus disease 2019 against a historic population of patients with influenza pneumonia who required extracorporeal membrane oxygenation. There were 51 patients who received extracorporeal membrane oxygenation due to coronavirus disease 2019 and 80 patients with influenza. At cannulation for extracorporeal membrane oxygenation, 37% of patients with coronavirus disease 2019 compared with 8% of patients with influenza had filling defects on CT pulmonary angiography (p = 0.0001). Catheter-associated deep vein thrombosis shown on ultrasound Doppler after decannulation was present in 53% with coronavirus disease 2019 versus 25% with influenza (p = 0.01). The rates of intracranial hemorrhage at the time of cannulation were 16% with coronavirus disease 2019 and 14% with influenza (p = 0.8). Elevated D-dimer levels were seen in both conditions and were significantly higher in those with pulmonary thromboembolism than those without in coronavirus disease 2019 (p = 0.02). Fibrinogen and C-reactive protein levels were significantly higher in those with coronavirus disease 2019 than influenza (p < 0.01). Conclusions: Significant rates of pulmonary thromboembolism and of catheter-associated deep vein thrombosis were seen in both viral infections but were greater in those requiring the use of extracorporeal membrane oxygenation in coronavirus disease 2019 than for influenza. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Doyle designed the study, collected data, performed data analysis, and wrote the article. Dr. Hunt designed the study and wrote the article. Dr. Sanderson collected data, performed data analysis, and reviewed the article. Drs. Zhang, Mak, and Benedetti collected data and reviewed the article. Drs. Breen, Camporota, and Barrett designed the study and reviewed the article. Dr. Retter designed the study, collected data, performed data analysis, and reviewed the article. Dr. Hunt disclosed that she is the Medical Director of Thrombosis UK. Dr. Barrett received research and educational support from Maquet and ALung Incorporated. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Andrew. Doyle@gstt.nhs.uk Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: To compare Acute Physiology and Chronic Health Evaluation-IV–adjusted mortality and length of stay outcomes of adult ICU patients who tested positive for coronavirus disease 2019 with patients admitted to ICU with other viral pneumonias including a subgroup with viral pneumonia and concurrent acute respiratory distress syndrome (viral pneumonia-acute respiratory distress syndrome). Design: Retrospective review of Acute Physiology and Chronic Health Evaluation data collected from routine clinical care. Setting: Forty-three hospitals contributing coronavirus disease 2019 patient data between March 14, and June 17, 2020, and 132 hospitals in the United States contributing data on viral pneumonia patients to the Acute Physiology and Chronic Health Evaluation database between January 1, 2014, and December 31, 2019. PATIENTS AND MEASUREMENTS: One thousand four hundred ninety-one patients with diagnosis of coronavirus disease 2019 infection and 4,200 patients with a primary (n = 2,544) or secondary (n = 1,656) admitting diagnosis of noncoronavirus disease viral pneumonia receiving ICU care. A subset of 202 viral pneumonia patients with concurrent acute respiratory distress syndrome was examined separately. Interventions: None. MAIN RESULTS: Mean age was 63.4 for coronavirus disease (p = 0.064) versus 64.1 for viral pneumonia. Acute Physiology and Chronic Health Evaluation-IV scores were similar at 56.7 and 55.0, respectively (p = 0.060), but gender and ethnic distributions differed, as did PaO2 to FIO2 ratio and WBC count at admission. The hospital standardized mortality ratio (95% CI) was 1.52 (1.35–1.68) for coronavirus disease patients and 0.82 (0.75–0.90) for viral pneumonia patients. In the coronavirus disease group, ICU and hospital length of stay were 3.1 and 3.0 days longer than in viral pneumonia patients. Standardized ICU and hospital length of stay ratios were 1.13 and 1.46 in the coronavirus disease group versus 0.95 and 0.94 in viral pneumonia patients. Forty-seven percent of coronavirus disease patients received invasive or noninvasive ventilatory support on their first ICU day versus 65% with viral pneumonia. Ventilator days in survivors were longer in coronavirus disease (10.4 d) than in viral pneumonia (4.3 d) patients, except in the viral pneumonia-acute respiratory distress syndrome subgroup (10.2 d) Conclusions: Severity-adjusted mortality and length of stay are higher for coronavirus disease 2019 patients than for viral pneumonia patients admitted to ICU. Coronavirus disease patients also have longer time on ventilator and ICU length of stay, comparable with the subset of viral pneumonia patients with concurrent acute respiratory distress syndrome. Mortality and length of stay increase with age and higher scores in both populations, but observed to predicted mortality and length of stay are higher than expected with coronavirus disease patients across all severity of illness levels. These findings have implications for benchmarking ICU outcomes during the coronavirus disease 2019 pandemic. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Higgins received funding from Cerner. Ms. Stark, Ms. Henson, and Ms. Freeseman-Freeman disclosed that they are employees of Cerner. For information regarding this article, E-mail: higginstl@yahoo.com Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia. Methods We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019. Results Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC. Conclusion This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.

Recently, a mobile tigecycline resistance module tmexCD1-toprJ1 was reported in K. pneumoniae (1, 2)....

Abstract Purpose We report on the first identified cluster of the B.1.1.7 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the northeast of Italy. Methods The cluster was recognized in January 2021 with an epidemiological started from the hospitalization of a 68-year-old man suffering from coronavirus disease 2019 (COVID-19) related pneumonia and we surprisingly found three families involved in the same cluster. Results We retrospectively rebuilt the pathway of infection and performed a virological analysis. Conclusion This allow us to make clear the very high attack rate and the great infective capacity of this B.1.1.7 variant of SARS-CoV-2.

Introduction In low-income and middle-income countries, pneumonia remains the leading cause of illness and death in children<5 years. The recommended tool for diagnosing paediatric pneumonia is the interpretation of chest X-ray images, which is difficult to standardise and requires trained clinicians/radiologists. Current automated computational tools have primarily focused on assessing adult pneumonia and were trained on images evaluated by a single specialist. We aim to provide a computational tool using a deep-learning approach to diagnose paediatric pneumonia using X-ray images assessed by multiple specialists trained by the WHO expert X-ray image reading panel. Methods and analysis Approximately 10 000 paediatric chest X-ray images are currently being collected from an ongoing WHO-supported surveillance study in Bangladesh. Each image will be read by two trained clinicians/radiologists for the presence or absence of primary endpoint pneumonia (PEP) in each lung, as defined by the WHO. Images whose PEP labels are discordant in either lung will be reviewed by a third specialist and the final assignment will be made using a majority vote. Convolutional neural networks will be used for lung segmentation to align and scale the images to a reference, and for interpretation of the images for the presence of PEP. The model will be evaluated against an independently collected and labelled set of images from the WHO. The study outcome will be an automated method for the interpretation of chest radiographs for diagnosing paediatric pneumonia. Ethics and dissemination All study protocols were approved by the Ethical Review Committees of the Bangladesh Institute of Child Health, Bangladesh. The study sponsor deemed it unnecessary to attain ethical approval from the Academic and Clinical Central Office for Research and Development of University of Edinburgh, UK. The study uses existing X-ray images from an ongoing WHO-coordinated surveillance. All findings will be published in an open-access journal. All X-ray labels and statistical code will be made openly available. The model and images will be made available on request.

Accumulating evidence shows that nervous system governs host immune responses; however, how -aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1β (IL-1β) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region. KID3 regulates oxidative phosphorylation (OXPHOS) via targeting the expression of OXPHOS-related genes and is also critical for NLRP3–ASC–caspase-1 complex formation. Likewise, GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo, including lipopolysaccharide-induced sepsis, infection-induced pneumonia, and high-fat diet-induced obesity. Together, we propose that targeting GABAergic system (e.g., GABA transporter) could provide previously unidentified therapeutic opportunities for the macrophage-associated diseases.

Abstract Background Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. Methods A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. Results Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. Conclusion Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.

Journal of Medical Virology, Volume 93, Issue 5, Page 2979-2987, May 2021.

To assess the effectiveness of corticosteroids among older adults with COVID-19 pneumonia requiring oxygen.

by Chang Hee Han, Misuk Kim, Jin Tae Kwak Coronavirus disease 2019 (COVID-19) has been spread out all over the world. Although a real-time reverse-transcription polymerase chain reaction (RT-PCR) test has been used as a primary diagnostic tool for COVID-19, the utility of CT based diagnostic tools have been suggested to improve the diagnostic accuracy and reliability. Herein we propose a semi-supervised deep neural network for an improved detection of COVID-19. The proposed method utilizes CT images in a supervised and unsupervised manner to improve the accuracy and robustness of COVID-19 diagnosis. Both labeled and unlabeled CT images are employed. Labeled CT images are used for supervised leaning. Unlabeled CT images are utilized for unsupervised learning in a way that the feature representations are invariant to perturbations in CT images. To systematically evaluate the proposed method, two COVID-19 CT datasets and three public CT datasets with no COVID-19 CT images are employed. In distinguishing COVID-19 from non-COVID-19 CT images, the proposed method achieves an overall accuracy of 99.83%, sensitivity of 0.9286, specificity of 0.9832, and positive predictive value (PPV) of 0.9192. The results are consistent between the COVID-19 challenge dataset and the public CT datasets. For discriminating between COVID-19 and common pneumonia CT images, the proposed method obtains 97.32% accuracy, 0.9971 sensitivity, 0.9598 specificity, and 0.9326 PPV. Moreover, the comparative experiments with respect to supervised learning and training strategies demonstrate that the proposed method is able to improve the diagnostic accuracy and robustness without exhaustive labeling. The proposed semi-supervised method, exploiting both supervised and unsupervised learning, facilitates an accurate and reliable diagnosis for COVID-19, leading to an improved patient care and management.

To externally validate community acquired pneumonia (CAP) tools on patients hospitalized with COVID-19 pneumonia from two distinct countries, and compare its performance to recently developed COVID-19 mortality risk stratification tools.

Abstract Background Older patients hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. Activity of daily living (ADL) is associated with clinical outcomes in older patients. We aimed to investigate the prognostic value of ADL upon admission on the in-hospital mortality in older patients with CAP. Methods We conducted a retrospective cohort study involving patients aged ≥65 years admitted to Beijing Chao-Yang hospital due to CAP between June 2012 and June 2020. ADL evaluation upon admission was performed by Barthel Index (BI). Data from all patients were extracted from the electronic medical records. Results Four thousand eight hundred eighty patients were included, 131 patients (2.7%) died during their hospitalization. Median BI in the Deceased group was 45 (20–65), Deceased group had lower BI scores than Survivors group (p < 0.001). Low BI (< 60) was more frequent in patients who died in the hospital than in patients discharged alive (69.5% vs. 13%, p < 0.001). In-hospital mortality was higher among patients with worse ADL upon admission (BI< 60) compared to those BI≥60 (12.6% vs. 0.9%). The worse ADL upon admission (BI< 60) was associated with an increase in the risk of death during CAP hospitalization, worse ADL upon admission (BI< 60) showed an odds ratio (OR) for in-hospital mortality of 7.53 (95%CI: 2.77–20.48; P < 0.01). This association remained significant after adjustment for age, comorbid conditions, respiratory failure, pathogens and laboratory findings (OR, 3.74; 95%CI, 2.37–5.91; P < 0.01). Receiver operating characteristic (ROC) curve revealed that BI upon admission is a predictor related to in-hospital mortality in elderly patients, the area under the ROC curve of BI in predicting in-hospital mortality was 0.81 (with 95% confidence interval: 0.78–0.85). The predictive value of ADL upon admission was better than age in our study population. Conclusion Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia.

Abstract Background Currently, the association of nutritional risk screening score with the development of nonventilator hospital-acquired pneumonia (NV-HAP) is unknown. This study investigated whether nutritional risk screening score is an independent predictor of NV-HAP. Methods This retrospective cohort study was conducted between September 2017 and June 2020 in a tertiary hospital in China. The tool of Nutritional Risk Screening 2002 (NRS-2002) was used for nutritional risk screening. A total score of ≥3 indicated a patient was “at nutritional risk.” Logistic regression was applied to explore the association between the NRS score and NV-HAP. Results A total of 67,280 unique patients were included in the study. The incidence of NV-HAP in the cohort for the NRS < 3 and ≥ 3 NRS group was 0.4% (232/62702) and 2.6% (121/4578), respectively. In a multivariable logistic regression model adjusted for all of the covariates, per 1-point increase in the NRS score was associated with a 30% higher risk of NV-HAP (OR = 1.30; 95%CI:1.19–1.43). Similarly, patients with NRS score ≥ 3 had a higher risk of NV-HAP with an odds ratio (OR) of 2.06 (confidence interval (CI): 1.58–2.70) than those with NRS score < 3. Subgroup analyses indicated that the association between the NRS score and the risk of NV-HAP was similar for most strata. Furthermore, the interaction analyses revealed no interactive role in the association between NRS score and NV-HAP. Conclusion NRS score is an independent predictor of NV-HAP, irrespective of the patient’s characteristics. NRS-2002 has the potential as a convenient tool for risk stratification of adult hospitalized patients with different NV-HAP risks.

by Simona Iftimie, Ana F. López-Azcona, Immaculada Vallverdú, Salvador Hernández-Flix, Gabriel de Febrer, Sandra Parra, Anna Hernández-Aguilera, Francesc Riu, Jorge Joven, Natàlia Andreychuk, Gerard Baiges-Gaya, Frederic Ballester, Marc Benavent, José Burdeos, Alba Català, Èric Castañé, Helena Castañé, Josep Colom, Mireia Feliu, Xavier Gabaldó, Diana Garrido, Pedro Garrido, Joan Gil, Paloma Guelbenzu, Carolina Lozano, Francesc Marimon, Pedro Pardo, Isabel Pujol, Antoni Rabassa, Laia Revuelta, Marta Ríos, Neus Rius-Gordillo, Elisabet Rodríguez-Tomàs, Wojciech Rojewski, Esther Roquer-Fanlo, Noèlia Sabaté, Anna Teixidó, Carlos Vasco, Jordi Camps, Antoni Castro Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.

Journal of Medical Virology, Accepted Article.

Pulmonary coagulopathy is intrinsic to pulmonary inflammation, occurs in patients with different types of lung injury, and is one of the potential mediators of harm caused by mechanical ventilation.1 Locally applied anticoagulants, such as heparin, could affect bronchoalveolar haemostasis, including fibrin deposition in the alveoli and possibly also in the vascular compartment.1 Although several clinical studies have shown that nebulised heparin mitigates both onset and progression of lung injury, one meta-analysis2 did not confirm any benefit.

by Jahanzeb Malik, Asmara Malik, Muhammad Javaid, Tayyaba Zahid, Uzma Ishaq, Muhammad Shoaib Background and objective Coronavirus disease 2019 (COVID-19) is an on-going epidemic with a multitude of long-ranging effects on the physiological balance of the human body. It can cause several effects on thyroid functions as well. We aimed to assess the lasting sequelae of COVID-19 on thyroid hormone and the clinical course of the disease as a result. Methods Out of 76 patients, 48 patients of COVID-19 positive and 28 patients of COVID-19 negative polymerase chain reaction (PCR) were assessed for thyroid functions, IL-6, and Procalcitonin between moderate, severe, and critical pneumonia on HRCT. Results Seventy-five percent of patients with COVID-19 had thyroid abnormalities and higher IL-6 levels (76.10 ± 82.35 vs. 6.99 ± 3.99, 95% CI 52.18–100.01, P-value…

by Jing Jiao, Zhen Li, Xinjuan Wu, Jing Cao, Ge Liu, Ying Liu, Fangfang Li, Chen Zhu, Baoyun Song, Jingfen Jin, Yilan Liu, Xianxiu Wen, Shouzhen Cheng, Xia Wan Background Mortality among patients with hospital-acquired pneumonia (HAP) is quite high; however, information on risk factors for short-term mortality in this population remains limited. The aim of the current study was to identify the risk factors for mortality in bedridden patients with HAP during a 3-month observation period. Methods A secondary data analysis was conducted. In total, 1141 HAP cases from 25 hospitals were included in the analysis. Univariate and multilevel regression analyses were performed to identify the risk factors for mortality. Results During the 3-month observation period, there were 189 deaths among bedridden patients with HAP. The mortality rate in this study was 16.56%. Multilevel regression analysis showed that ventilator-associated pneumonia (OR = 2.034, 95%CI: 1.256, 3.296, p = 0.004), pressure injuries (OR = 2.202, 95%CI: 1.258, 3.852, p = 0.006), number of comorbidities (OR = 1.076, 95%CI: 1.016,1.140, p = 0.013) and adjusted Charlson Comorbidity Index score (OR = 1.210, 95%CI: 1.090, 1.343, p<0.001) were associated with an increased risk of mortality, while undergoing surgery with general anaesthesia (OR = 0.582, 95%CI: 0.368, 0.920, p = 0.021) was associated with a decreased risk of mortality. Conclusions The identification of risk factors associated with mortality is an important step towards individualizing care plans. Our findings may help healthcare workers select high-risk patients for specific interventions. Further study is needed to explore whether appropriate interventions against modifiable risk factors, such as reduced immobility complications or ventilator-associated pneumonia, could improve the prognoses.

by Adejumoke Idowu Ayede, Oluwakemi Oluwafunmi Ashubu, Kayode Raphael Fowobaje, Samira Aboubaker, Yasir Bin Nisar, Shamim Ahmad Qazi, Rajiv Bahl, Adegoke Gbadegesin Falade Introduction Neonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment. Methods This implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented. Results From 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7–59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0–6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7–59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation. Conclusions When a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities. Registration Trial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369.

Objectives Domestic epidemiological studies are needed to ascertain the disease burden of bacteraemia in individual countries. This study aimed to evaluate the domestic trends in paediatric and adult bacteraemia in Japan. Setting Laboratory-based surveillance was used to obtain data from 592 hospitals located throughout Japan. Participants The study was conducted using the results of 827 780 and 3 512 524 blood culture tests obtained from children and adults, respectively, between January 2010 and December 2016. Outcome measures We analysed the temporal trends in specific bacterial species (Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Haemophilus influenzae, Listeria monocytogenes and Neisseria meningitidis) detected from the blood cultures of children and adults. For children aged ≤2 years, the data were analysed for each year of age. The proportions of bacteraemia-positive results among the patients were also evaluated. Results The number of bacteraemia-positive samples over the study period was 47,125/827,855 (5.7%) in children and 959,765/3,513,885 (27.3%) in adults. S. pneumoniae was the most frequent cause of bacteraemia in children in 2010. However, after 2011, S. aureus bacteraemia was the most frequent, followed by S. pneumoniae and E. coli. E. coli bacteraemia showed significant increases in both children and adults. In children, S. pneumoniae and H. influenzae bacteraemia decreased from 2010 to 2013. However, S. pneumoniae bacteraemia case numbers stabilised from 2013, whereas H. influenzae bacteraemia cases continued to decrease until 2016. Conclusion The results suggest that the introduction of the 13-valent pneumococcal conjugate vaccine did not substantially affect disease occurrence. In contrast to the decreasing trends in H. influenzae and S. pneumoniae bacteraemia, S. aureus, E. coli and S. agalactiae bacteraemia showed increasing trends. These findings shed light on recent temporal trends in bacteraemia in both children and adults in Japan.

Third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae represent a major threat to human health. Here, we captured 288 3GC-R Enterobacteriaceae clinical isolates from 264 patients presenting at a regional Australian hospital over a 14-month period. Alongside routine mass spectrometry speciation and antibiotic sensitivity testing, isolates were examined using rapid (~40 min) real-time PCR assays targeting the most common extended spectrum β-lactamases (ESBLs; blaCTX-M-1 and blaCTX-M-9 groups, plus blaTEM, blaSHV, and an internal 16S ribosomal DNA control). AmpC CMY β-lactamase (blaCMY) prevalence was also examined. Escherichia coli (80.2%) and Klebsiella pneumoniae (17.0%) were dominant, with Klebsiella oxytoca, Klebsiella aerogenes and Enterobacter cloacae infrequently identified. Ceftriaxone and cefoxitin resistance were identified in 97.0% and 24.5% of E. coli and K. pneumoniae isolates, respectively. Consistent with global findings in Enterobacteriaceae, most (98.3%) isolates harbored at least one β-lactamase gene, with 144 (50%) encoding blaCTX-M-1 group, 92 (31.9%) blaCTX-M-9 group, 48 (16.7%) blaSHV, 133 (46.2%) blaTEM, and 34 (11.8%) blaCMY. A subset of isolates (n=98) were subjected to whole-genome sequencing (WGS) to identify the presence of cryptic resistance determinants, and to verify genotyping accuracy. WGS of β-lactamase negative or carbapenem-resistant isolates identified uncommon ESBLs and carbapenemases, including blaNDM and blaIMP, and confirmed all PCR-positive genotypes. We demonstrate that our PCR assays enable the rapid and cost-effective identification of ESBLs in the hospital setting, which has important infection control and therapeutic implications.

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airways dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that was associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients, and indicates avenues for antimicrobial stewardship and metabolic re-equilibrium in IFI.

Abstract Background Limited clinical studies describe the pharmacodynamics of fosfomycin (FOS), tigecycline (TGC) and colistin methanesulfonate (CMS) in combination against KPC-producing Klebsiella pneumoniae (KPC-Kp). Population pharmacokinetic models were used in our study. Monte Carlo simulation was conducted to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR) of each agent alone and in combination against KPC-Kp in patients with normal or decreased renal function. Results The simulated regimen of FOS 6 g q8h reached ≥90% PTA against a MIC of 64 mg/L in patients with normal renal function. For patients with renal impairment, FOS 4 g q8h could provide sufficient antimicrobial coverage against a MIC of 128 mg/L. And increasing the daily dose could result to the cut-off value to 256 mg/L in decreased renal function. For TGC, conventional dosing regimens failed to reach 90% PTA against a MIC of 2 mg/L. Higher loading and daily doses (TGC 200/400 mg loading doses followed by 100 mg q12h/200 mg q24h) were needed. For CMS, none achieved 90% PTA against a MIC of 2 mg/L in normal renal function. Against KPC-Kp, the regimens of 200/400 mg loading dose followed by 100 q12h /200 mg q24h achieved > 80% CFRs regardless of renal function, followed by CMS 9 million IU loading dose followed by 4.5/3 million IU q12h in combination with FOS 8 g q8h (CFR 75–91%). Conclusions The use of a loading dose and high daily dose of TGC and CMS in combination with FOS can provide sufficient antimicrobial coverage against critically ill patients infected with KPC-Kp.

Duration of antibiotic therapy is a key decision in the management of community-acquired pneumonia, the number one cause of infectious disease mortality in developed countries such as the USA.1 In current US guidelines, therapy is recommended for a minimum of 5 days in patients admitted to hospital, provided that the patient has been afebrile for at least 48 h, initial therapy was appropriate, there is no more than one clinical instability, and no signs of extrapulmonary infection.1 Shortening the duration of therapy could lead to fewer antibiotic side-effects, less pressure for antimicrobial resistance, reduced costs, and a reduced risk of bacterial superinfection.

Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption.

Abstract Background Proper detection of disease-causing organisms is very critical in controlling the course of outbreaks and avoiding large-scale epidemics. Nonetheless, availability of resources to address these gaps have been difficult due to limited funding. This report sought to highlight the importance of in-country partners and non-governmental organizations in improving detection of microbiological organisms in Ghanaian Public Health Laboratories (PHLs). Methods/context This study was conducted between June, 2018 to August, 2019. U. S CDC engaged the Centre for Health Systems Strengthening (CfHSS) through the Association of Public Health Laboratories to design and implement strategies for strengthening three PHLs in Ghana. An assessment of the three PHLs was done using the WHO/CDS/CSR/ISR/2001.2 assessment tool. Based on findings from the assessments, partner organizations (CfHSS/APHL/CDC) serviced and procured microbiological equipment, laboratory reagents and logistics. CfHSS provided in-house mentoring and consultants to assist with capacity building in detection of epidemic-prone infectious pathogens by performing microbiological cultures and antimicrobial susceptibility tests. Results A total of 3902 samples were tested: blood (1107), urine (1742), stool (249) and cerebrospinal fluid (CSF) (804). All-inclusive, 593 pathogenic bacteria were isolated from blood cultures (70; 11.8%); urine cultures (356; 60%); stool cultures (19; 3.2%) and from CSF samples (148; 25%). The most predominant pathogens isolated from blood, urine and stool were Staphylococcus aureus (22/70; 31%), Escherichia coli (153/356; 43%) and Vibrio parahaemolyticus (5/19; 26.3%), respectively. In CSF samples, Streptococcus pneumoniae was the most frequent pathogen detected (80/148; 54.1%). New bacterial species such as Pastuerella pneumotropica, Klebsiella oxytoca, Vibrio parahaemolyticus, and Halfnia alvei were also identified with the aid of Analytical Profile Index (API) kits that were introduced as part of this implementation. Streptococcus pneumoniae and Neisseria meningitidis detections in CSF were highest during the hot dry season. Antimicrobial susceptibility test revealed high rate of S. aureus, K. pneumoniae and E. coli resistance to gentamicin (35–55%). In urine, E. coli was highly resistant to ciprofloxacin (39.2%) and ampicillin (34%). Conclusion Detection of epidemic-prone pathogens can be greatly improved if laboratory capacity is strengthened. In-country partner organizations are encouraged to support this move to ensure accurate diagnosis of diseases and correct antimicrobial testing.

To analyse the strains collected during a one-year survey of ceftazidime-avibactam (CZA)-resistant KPC-producing Klebsiella pneumoniae (KPC-Kp), in order to investigate the molecular mechanisms potentially responsible for their resistant phenotype.

Introduction Parapneumonic effusion and empyema are common complications of paediatric pneumonia. Acceptable treatment modalities for large parapneumonic effusions include antibiotics alone or in conjunction with surgical interventions. Clear guidelines on the best treatment approach are lacking and mostly based on evidence prior to widespread pneumococcal conjugate 13-valent vaccination (PCV-13). Methods and analysis A living systematic review and network meta-analysis will be performed comparing the five treatment modalities: (1) antibiotics alone; (2) chest tube drainage without fibrinolytics; (3) chest tube drainage with fibrinolytics; (4) video-assisted thoracoscopic surgery and (5) open thoracotomy. The review protocol is reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Eligible studies are randomised controlled trials comparing any pair of interventions in paediatric patients with empyema or parapneumonic effusion. The following databases will be searched: Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, LILACS and Google Scholar. Citation screening and data extraction will be completed using a validated crowdsourcing methodology using InsightScope. To assess the risk of bias, we will use the revised Cochrane risk of bias tool for randomised trials. The primary outcome of the study is the length of stay. Secondary outcomes are (1) periprocedural complications and (2) need for re-intervention. A frequentist network meta-analysis design will be implemented with a random-effects model comparing different interventions. In a subgroup analysis, studies and patients will be stratified by the size of pleural effusion and the date of trial (pre/post-PCV-13). Eligible citations and available results will be uploaded to an online database, hosted on Open Science Framework. The database will be updated at least every 4 months with any newly published research. Ethics and dissemination No ethics review is required for this study. Results will be published in a peer-reviewed journal. Data will be available as part of an online database summarising the evidence of this living systematic review. PROSPERO registration Pending peer review.

by Lucio Manenti, Umberto Maggiore, Enrico Fiaccadori, Tiziana Meschi, Anna Degli Antoni, Antonio Nouvenne, Andrea Ticinesi, Nicoletta Cerundolo, Beatrice Prati, Marco Delsante, Ilaria Gandoflini, Lorenzo Donghi, Micaela Gentile, Maria Teresa Farina, Vincenzo Oliva, Cristina Zambrano, Giuseppe Regolisti, Alessandra Palmisano, Caterina Caminiti, Enrico Cocchi, Carlo Ferrari, Leonardo V. Riella, Paolo Cravedi, Licia Peruzzi Objectives Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. Methods This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. Results Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. Conclusion In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.

by Pierre Edwige L. Fils, Pascal Cholley, Houssein Gbaguidi-Haore, Didier Hocquet, Marlène Sauget, Xavier Bertrand The worldwide spread of Klebsiella pneumoniae producing extended-spectrum β-lactamase (ESBL-Kp) is a significant threat. Specifically, various pandemic clones of ESBL-Kp are involved in hospital outbreaks and caused serious infections. In that context, we assessed the phenotypic and molecular features of a collection of ESBL-Kp isolates in a French university hospital and evaluated the occurrence of potential cross-transmissions. Over a 2-year period (2017–2018), 204 non-duplicate isolates of ESBL-Kp were isolated from clinical (n = 118, 57.8%) or screening (n = 86, 42.2%) sample cultures. These isolates were predominantly resistant to cotrimoxazole (88.8%) and ofloxacin (82.8%) but remained susceptible to imipenem (99.3%) and amikacin (93.8%). CTX-M-15 was the most frequent ESBL identified (83.6%). Multilocus sequence typing and pulse-field gel electrophoresis analysis showed an important genetic variability with 41 sequence types (ST) and 50 pulsotypes identified, and the over representation of the international epidemic clones ST307 and ST405. An epidemiological link attesting probable cross-transmission has been identified for 16 patients clustered in 4 groups during the study period. In conclusion, we showed here the dissemination of pandemic clones of ESBL-Kp in our hospital on a background of clonal diversity.

Abstract Purpose SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features. Methods Non-systematic review. Results SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R0) is between 2 and 3, and the median incubation period is 5.7 (range 2–14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5–10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection’s fatality rate is 0.5–1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries. Conclusions Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

Abstract Purpose Legionella spp. pneumonia (LP) is a cause of community-acquired pneumonia (CAP) that requires early intervention. The median mortality rate varies from 4 to 11%, but it is higher in patients admitted to intensive care unit (ICU). The objective of this study is to identify predictors of ICU admission in patients with LP. Methods A single-center, retrospective, observational study conducted in an academic tertiary-care hospital in Pisa, Italy. Adult patients with LP consecutively admitted to study center from October 2012 to October 2019. Results During the study period, 116 cases of LP were observed. The rate of ICU admission was 20.7% and the overall 30-day mortality rate was 12.1%. Mortality was 4.3% in patients hospitalized in medical wards versus 41.7% in patients transferred to ICU (p < 0.001). The majority of patients (74.1%) received levofloxacin as definitive therapy, followed by macrolides (16.4%), and combination of levofloxacin plus a macrolide (9.5%). In the multivariate analysis, diabetes (OR 8.28, CI 95% 2.11–35.52, p = 0.002), bilateral pneumonia (OR 10.1, CI 95% 2.74–37.27, p = 0.001), and cardiovascular events (OR 10.91, CI 95% 2.83–42.01, p = 0.001), were independently associated with ICU admission, while the receipt of macrolides/levofloxacin therapy within 24 h from admission was protective (OR 0.20, CI 95% 0.05–0.73, p = 0.01). Patients who received a late anti-Legionella antibiotic (> 24 h from admission) underwent urinary antigen test later compared to those who received early active antibiotic therapy (2 [2–4] vs. 1 [1–2] days, p < 0.001). Conclusions Admission to ICU carries significantly increased mortality in patients with diagnosis of LP. Initial therapy with an antibiotic active against Legionella (levofloxacin or macrolides) reduces the probability to be transferred to ICU and should be provided in all cases until Legionella etiology is excluded.

Abstract Background Since the end of February 2020, the Coronavirus Disease 2019 (COVID-19) outbreak rapidly spread throughout Italy and other European countries, but limited information has been available about its characteristics in HIV-infected patients. Methods We have described a case series of patients with HIV infection and COVID-19 diagnosed at the S.Orsola Hospital (Bologna, Italy) during March and April, 2020. Results We reported a case series of 26 HIV-infected patients with COVID-19. Nineteen subjects were men, the median age was 54 years, 73% of patients had one or more comorbidities. Only 5 patients with interstitial pneumonia were hospitalized, but there were no admissions to intensive care unit and no deaths. Conclusions In our experience, COVID-19 associated with HIV infection had a clinical presentation comparable to the general population and was frequently associated with chronic comorbidities.

by Mariano Andrés, Jose-Manuel Leon-Ramirez, Oscar Moreno-Perez, José Sánchez-Payá, Ignacio Gayá, Violeta Esteban, Isabel Ribes, Diego Torrus-Tendero, Pilar González-de-la-Aleja, Pere Llorens, Vicente Boix, Joan Gil, Esperanza Merino, on behalf of COVID19-ALC research group Introduction This study analyzed the impact of a categorized approach, based on patients’ prognosis, on major outcomes and explanators in patients hospitalized for COVID-19 pneumonia in an academic center in Spain. Methods Retrospective cohort study (March 3 to May 2, 2020). Patients were categorized according to the followed clinical management, as maximum care or limited therapeutic effort (LTE). Main outcomes were all-cause mortality and need for invasive mechanical ventilation (IMV). Baseline factors associated with outcomes were analyzed by multiple logistic regression, estimating odds ratios (OR; 95%CI). Results Thirty-hundred and six patients were hospitalized, median age 65.0 years, 57.8% males, 53.3% Charlson index ≥3. The overall all-cause fatality rate was 15.0% (n = 46). Maximum care was provided in 238 (77.8%), IMV was used in 38 patients (16.0%), and 5.5% died. LTE was decided in 68 patients (22.2%), none received IMV and fatality was 48.5%. Independent risk factors of mortality under maximum care were lymphocytes 15ng/L and hypotension. Advanced age, lymphocytes 240pg/mL independently associated with IMV requirement. Conclusion Overall fatality in the cohort was 15% but markedly varied regarding the decided approach (maximum care versus LTE), translating into nine-fold higher mortality and different risk factors.