Host protease activity classifies pneumonia etiology.

Community-acquired pneumonia (CAP) has been brought to the forefront of global health priorities due to the COVID-19 pandemic. However, classification of viral versus bacterial pneumonia etiology remains a significant clinical challenge. To this end, we have engineered a panel of activity-based nanosensors that detect the dysregulated activity of pulmonary host proteases implicated in the response to pneumonia-causing pathogens and produce a urinary readout of disease. The nanosensor targets were selected based on a human protease transcriptomic signature for pneumonia etiology generated from 33 unique publicly available study cohorts. Five mouse models of bacterial or viral CAP were developed to assess the ability of the nanosensors to produce etiology-specific urinary signatures. Machine learning algorithms were used to train diagnostic classifiers that could distinguish infected mice from healthy controls and differentiate those with bacterial versus viral pneumonia with high accuracy. This proof-of-concept diagnostic approach demonstrates a way to distinguish pneumonia etiology based solely on the host proteolytic response to infection.

Convolutional Sparse Support Estimator-Based COVID-19 Recognition From X-Ray Images.

Coronavirus disease (COVID-19) has been the main agenda of the whole world ever since it came into sight. X-ray imaging is a common and easily accessible tool that has great potential for COVID-19 diagnosis and prognosis. Deep learning techniques can generally provide state-of-the-art performance in many classification tasks when trained properly over large data sets. However, data scarcity can be a crucial obstacle when using them for COVID-19 detection. Alternative approaches such as representation-based classification [collaborative or sparse representation (SR)] might provide satisfactory performance with limited size data sets, but they generally fall short in performance or speed compared to the neural network (NN)-based methods. To address this deficiency, convolution support estimation network (CSEN) has recently been proposed as a bridge between representation-based and NN approaches by providing a noniterative real-time mapping from query sample to ideally SR coefficient support, which is critical information for class decision in representation-based techniques. The main premises of this study can be summarized as follows: 1) A benchmark X-ray data set, namely QaTa-Cov19, containing over 6200 X-ray images is created. The data set covering 462 X-ray images from COVID-19 patients along with three other classes; bacterial pneumonia, viral pneumonia, and normal. 2) The proposed CSEN-based classification scheme equipped with feature extraction from state-of-the-art deep NN solution for X-ray images, CheXNet, achieves over 98% sensitivity and over 95% specificity for COVID-19 recognition directly from raw X-ray images when the average performance of 5-fold cross validation over QaTa-Cov19 data set is calculated. 3) Having such an elegant COVID-19 assistive diagnosis performance, this study further provides evidence that COVID-19 induces a unique pattern in X-rays that can be discriminated with high accuracy.

Risk Factors for Severe Pneumonia According to WHO 2005 Criteria Definition Among Children <5 Years of Age in Thai Binh, Vietnam: A Case-Control Study.

Vietnam is one of the 15 countries where the prevalence of child pneumonia is highest. It is a major cause of admission in pediatric hospitals. However, little is known on the burden of severe pneumonia and their risk factors in children <5 years of age in Vietnam. A case-control study was conducted among children aged 2-59 months presenting with pneumonia at the Pediatric Provincial Hospital of Thai Binh. Cases were children with severe pneumonia while controls included those with non-severe pneumonia as defined by the World Health Organization (WHO) classification of 2005. Eighty-three cases and 83 controls were included. Sex ratio was 2.19. Children with severe pneumonia were significantly less likely to receive antibiotics preadmission compared to children with non-severe pneumonia [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06-0.42]. The main risk factors of severe pneumonia were a lack of immunization (OR = 4.77, 95% CI = 1.80-12.65), an exposure to cigarette smoke (OR = 3.87, 95% CI = 1.62-9.23), and having a mother with a low level of education. Children with severe pneumonia were 25 times more likely to present with associated measles with p < 0.0001 and five times more likely to present with diarrhea than children with non-severe pneumonia (p < 0.0001). Improving immunization coverage, educating parents about the risks of passive smoking and the recognition of respiratory distress signs, and facilitating early antibiotic access for infants with acute pulmonary disease should reduce the burden of such illnesses. To implement a national, multicenter study about pneumonia in children, more precise inclusion criteria should be chosen, including radiological and/or biological assessment.

Treatment of community-acquired pneumonia. / Behandling av pneumoni oppstått utenfor sykehus.

BAKGRUNN: Helsedirektoratet gir ut nasjonale retningslinjer for antibiotikabruk i sykehus. For pneumoni oppstått utenfor sykehus anbefales penicillin ved mild til moderat pneumoni og penicillin i kombinasjon med gentamicin ved alvorlig pneumoni. Alvorlighetsgrad vurderes med CRB-65-kriteriene. Vi vet lite om etterlevelse av retningslinjene. METODE: Vi gjennomgikk journalene til pasienter innlagt med pneumoni med Streptococcus pneumoniae eller Haemophilus influenzae ved Infeksjonsmedisinsk avdeling ved Oslo universitetssykehus, Ullevål sykehus, i 2015 (N = 70) og undersøkte om behandlingen som ble gitt, var i samsvar med de nasjonale retningslinjene. RESULTATER: 24 (34 %) av pasientene fikk penicillin i monoterapi, 25 (36 %) fikk kombinasjonen penicillin og gentamicin, 14 (20 %) fikk kefalosporiner, mens 7 (10 %) fikk andre antibiotika. Totalt fikk 38 (54 %) pasienter empirisk antibiotika i henhold til retningslinjene. CRB-65-kriteriene ble ikke dokumentert hos noen av pasientene. 38 av 50 pasienter som fikk penicillin, fikk høyere doser enn anbefalt. 62 (89 %) pasienter fikk justert behandling etter at bakteriesvar forelå. Median lengde av antibiotikabehandling var 10 døgn (interkvartilintervall 8-11 døgn). FORTOLKNING: Bredspektrede antibiotika ble benyttet oftere enn retningslinjene skulle tilsi. Etter at bakteriesvar forelå, ble behandlingen justert i henhold til de nasjonale retningslinjene. Penicillindosene var ofte for høye og behandlingslengden for lang sammenholdt med de nasjonale retningslinjene.

Effect of enhanced feedback to hospitals that are part of an emerging clinical information network on uptake of revised childhood pneumonia treatment policy: study protocol for a cluster randomized trial.

BACKGROUND: The national pneumonia treatment guidelines in Kenya changed in February 2016 but such guideline changes are often characterized by prolonged delays in affecting practice. We designed an enhanced feedback intervention, delivered within an ongoing clinical network that provides a general form of feedback, aimed at improving and sustaining uptake of the revised pneumonia treatment policy. The objective was to determine whether an enhanced feedback intervention will improve correctness of classification and treatment of childhood pneumonia, compared to an existing approach to feedback, after nationwide treatment policy change and within an existing hospital network. METHODS/DESIGN: A pragmatic, cluster randomized trial conducted within a clinical network of 12 Kenyan county referral hospitals providing inpatient pediatric care to children (aged 2-59 months) with acute medical conditions between March and November 2016. The intervention comprised enhanced feedback (monthly written feedback incorporating goal setting, and action planning delivered by a senior clinical coordinator for selected pneumonia indicators) and this was compared to standard feedback (2-monthly written feedback on multiple quality of pediatric care indicators) both delivered within a clinical network promoting clinical leadership linked to mentorship and peer-to-peer support, and improved use of health information on service delivery. The 12 hospitals were randomized to receive either enhanced feedback (n = 6) or standard feedback (n = 6) delivered over a 9-month period following nationwide pneumonia treatment policy change. The primary outcome is the proportion of all admitted patients with pneumonia (fulfilling criteria for treatment with orally administered amoxicillin) who are correctly classified and treated in the first 24 h. The secondary outcome will be measured over the course of the admission as any change in treatment for pneumonia after the first 24 h. DISCUSSION: This trial protocol employs a pragmatic trial design during a period of nationwide change in treatment guidelines to address two high-priority areas within implementation research: promoting adoption of health policies and optimizing effectiveness of feedback. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02817971 . Registered retrospectively on 27 June 2016.

Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?

Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.

[Para- and Postpneumonic Pleural Empyema: Current Treatment Strategies in Children and Adults]. / Para- und postpneumonisches Pleuraempyem: aktuelle Behandlungsstrategien bei Kindern und Erwachsenen.

INTRODUCTION: Parapneumonic pleural effusions arise from pneumonia and may develop into pleural empyema (PE). PE is defined as collection of pus in the pleural space with secondary inflammation of the visceral and parietal pleura. This review article describes the current treatment strategies for para- and postpneumonic PE both in children and adults. MATERIAL AND METHODS: Selective literature research via Medline (key words: pleural empyema, pleural empyema in children, thoracic empyema) and presentation of our own clinical experience with therapy recommendations. RESULTS: The incidence of postpneumonic PE is increasing in both children and adults. PE is associated with a high morbidity and mortality if it is not treated early and adequate. Progression of PE follows a characteristic morphological course, which is classified in three stages: the exsudative, fibrinopurulent, and organizing phase. Treatment should be adapted to these three phases including systemic antibiotic therapy and drainage of the pleural space. Intrapleural fibrinolysis can be performed with good success independent of age in the transition of stage 1 and 2. In persistent PE (stage 2), thoracoscopic decortication is recommended to avoid progression into the organizing phase (stage 3) with the need of an open decortication. In debilitated elderly patients the increasing use of intrathoracic vacuum therapy (Mini-VAC/Mini-VAC-instill) offers an effective and less invasive therapy option. CONCLUSION: Para- and postpneumonic PE requires an individualized and stage adapted therapy using a combination of medical and surgical treatment strategies with the aims of removing the source of infection and ensuring re-establishment of lung expansion.

[Pneumonia in the elderly: are there any specificities? ]. / Pneumonie chez Le sujet âgé: y a-t-il des spécificités?

Pneumonia is one of the leading causes of death in the elderly. Streptococcus pneumoniae is the leading etiological agent, but the identification of a pathogen remains infrequent despite advances in microbiological methods. Antibiotic resistant organisms should be considered as potential causal agents in recently hospitalized patients and patients with recent antibiotic exposure and influenza during the flu season. The clinical diagnosis is difficult due to frequent atypical presentation. Prognostic scores are not always appropriate to predict the need for hospitalization in very old patients. Studies on the role of low-dose chest CT for the diagnosis, management and prevention should help improve the management of this disease in the future.

[Infectious pulmonary diseases]. / Infektiöse Lungenerkrankungen.

Infectious pulmonary diseases and pneumonias are important causes of death within the group of infectious diseases in Germany. Most cases are triggered by bacteria. The morphology of the inflammation is often determined by the agent involved but several histopathological types of reaction are possible. Histology alone is only rarely able to identify the causal agent; therefore additional microbiological diagnostics are necessary in most cases. Clinically cases are classified as community acquired and nosocomial pneumonia, pneumonia under immunosuppression and mycobacterial infections. Histologically, alveolar and interstitial as well as lobar and focal pneumonia can be differentiated.

International guidelines on tackling community-acquired pneumonia show major discrepancies between developed and developing countries.

AIM: The goal of this study was to compare the current guidelines on diagnosis and treatment of paediatric community-acquired pneumonia (CAP) in developing and developed countries. METHODS: A literature search was performed consulting the Medline, Embase, Current Contents, National Guideline Clearinghouse and Cochrane database, from January 2000 to March 2013. RESULTS: Twelve guidelines were selected: six from developed countries and six from developing countries. Major discrepancies between the diagnosis and treatment approaches recommended by guidelines covering developing and developed countries were revealed. The search also highlighted differences between recommendations issued in similar settings. CONCLUSION: The guidelines show wide variations and weak recommendations and further research is needed to improve clinical outcomes and make better use of resources.

The role of atypical pathogens in community-acquired pneumonia.

The term atypical pneumonia was first used in 1938, and by the 1970s it was widely used to refer to pneumonia due to Mycoplasma pneumoniae, Legionella pneumophila (or other Legionella species), and Chlamydophila pneumoniae. However, in the purest sense all pneumonias other than the classic bacterial pneumonias are atypical. Currently many favor abolition of the term atypical pneumonia.This review categorizes atypical pneumonia pathogens as conventional ones; viral agents and emerging atypical pneumonia pathogens. We emphasize viral pneumonia because with the increasing availability of multiplex polymerase chain reaction we can identify the agent(s) responsible for viral pneumonia. By using a sensitive assay for procalcitonin one can distinguish between viral and bacterial pneumonia. This allows pneumonia to be categorized as bacterial or viral at the time of admission to hospital or at discharge from the emergency department and soon thereafter further classified as to the etiology, which should be stated as definite or probable.

Nationwide survey on the 2005 Guidelines for the Management of Community-Acquired Adult Pneumonia: validation of differentiation between bacterial pneumonia and atypical pneumonia.

INTRODUCTION: The Japanese Respiratory Society Guidelines for the Management of Community-Acquired Pneumonia (CAP) in Adults (JRS 2005) was published as a revision of the Basic Concept for the Management of CAP in Adults (JRS 2000). To evaluate the JRS 2005 criteria for differentiating between disease types and assessing the status of antimicrobial agent use in initial treatment, we conducted a prospective survey. SUBJECTS AND METHODS: The survey was conducted from July 2006 to March 2007 as a nationwide joint study by 200 institutions. The study subjects included patients aged ≥16 years of age who had CAP, and patients who met the inclusion criteria were consecutively enrolled. Disease type differentiation based on JRS 2005 and JRS 2000 was conducted. Disease type diagnosis was also performed based on test results. The sensitivity and specificity of disease type differentiation were calculated. The antimicrobial agents used in the initial treatment were classified as recommended or non-recommended based on JRS 2005. The validity of non-recommended antimicrobial agent use was investigated. RESULTS: A total of 1875 patients were analyzed. Differentiation of atypical pneumonia using the JRS 2005 criteria had higher sensitivity and lower specificity than differentiation using the JRS 2000 criteria. The antimicrobial agents recommended by JRS 2005 were used as initial treatment in a low number of cases. The efficacy of the recommended antimicrobial agents was similar to that of the non-recommended agents. CONCLUSIONS: JRS 2005 is advantageous in terms of reducing the number of items used in disease type differentiation. The recommended antimicrobial agents used for the initial treatment are believed to be appropriate.

Community-acquired pneumonia in younger patients is an entity on its own.

Community-acquired pneumonia (CAP) is now most frequent in elderly patients. CAP in the younger patient has attracted much less attention. Therefore, we compared patients with CAP aged 18 to <65 yrs with those aged ≥ 65 yrs. Data from the prospective multicentre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database were analysed for potential differences in baseline characteristics, comorbidities, clinical presentation, microbial investigations, aetiologies, antimicrobial treatment and outcomes. Overall, 7,803 patients were studied. The proportion of younger patients (aged <65 yrs) was 52.3% (18 to <30 yrs 6.4%; <40 yrs 17.1%; <50 yrs 29.4%). Comorbidity was present in only half of the younger patients (46.6% versus 88.2%). Fever and chest pain were more common. Most younger patients presented with mild CAP (74.0% had a CRB-65 [corrected] score of 0 (confusion of new onset, [corrected] respiratory rate of ≥ 30 breaths · min(-1), blood pressure <90 mmHg or diastolic blood pressure ≤ 60 mmHg, age ≥ 65 yrs)). Overall, Streptococcus pneumoniae and Mycoplasma pneumoniae were the most frequent pathogens in the younger patients. Short-term mortality was very low (1.7% versus 8.2%) and even lower in patients without comorbidity (0.3% versus 2.4%). Long-term mortality was 3.2% versus 15.9%, also lower in patients without comorbidity (0.8% versus 6.1%). Most of the differences found clearly arise after the fifth or within the middle of the sixth decade. CAP in the younger patient is a clinically distinct entity.

Validity of pneumonia severity index and CURB-65 severity scoring systems in community acquired pneumonia in an Indian setting.

BACKGROUND: Little information is available from India regarding prognostic factors in patients with community acquired pneumonia (CAP). METHODS: Hospital-based prospective study to test the validity of pneumonia severity index (PSI) and the confusion, urea, respiratory rate, blood pressure, age over 65 years (CURB-65) risk scoring systems in patients with CAP (n=150). RESULTS: Although both CURB-65 class > or = III and PSI class > or = IV were 100% sensitive in predicting death, CURB-65 class > or = III had a higher specificity (74.6%) than PSI class > or = IV (52.2%) when used to predict death. In both PSI and CURB-65 risk scoring systems, mortality rate, need for intensive care unit (ICU) admission, prolonged need for intravenous (I.V.) antibiotics, prolonged duration of hospital stay and need for admission to ICU increased progressively with increasing scores. The PSI class > or = IV was more sensitive in predicting ICU admission than CURB-65. The duration of hospital stay was found to have a weak but significant correlation with PSI and CURB-65 criteria. Defervescence time also had a very weak but significant correlation with PSI and CURB-65 criteria. Duration of I.V. antibiotics had a moderately strong correlation with CURB-65 criteria but a weak correlation with PSI criteria. CONCLUSIONS: Both PSI and CURB-65 were found to have equal sensitivity to predict death from CAP. Specificity of CURB-65 was higher than that of PSI. However, PSI was more sensitive in predicting ICU admission than CURB-65.

[Comparison of three prediction rules for prognosis in community acquired pneumonia: Pneumonia Severity Index (PSI), CURB-65, and A-DROP].

UNLABELLED: Several severity scores have been proposed to predict patient outcome and guide initial management of patients with community acquired pneumonia (CAP). The Japan Respiratory Society (JRS) has proposed new predicting scores, A-DROP system (score 0-5, Age : male 70 years and more, female 75 years and more, BUN > 21 mg/dl, SpO2 < 90% or PaO2 < 60 Torr, confusion, systolic blood pressure < 90 mmHg). We aimed to compare the predictive value of these instruments regarding 30-day mortality. METHODS: All patients with an admission diagnosis of CAP from April 2002-March 2006 were reviewed. Clinical and laboratory features at presentation on electrical medical records were used to calculate severity scores using the Pneumonia Severity Index (PSI), CURB-65 (2004) and A-DROP (2005). Patients were categorized into PSI risk classes (I-V) and CURB-65 (0-5) and A-DROP (0-5) risk strata. RESULTS: Consecutive 523 patients (61% male) of mean age 70.5 years were included in the analysis. Thirty-one (5.9%) patients died and 12 (2.2%) patients required ventilatory support. ROC analysis for predicting mortality at 30 days showed that A-DROP score has similar power for short-term mortality to PSI, and slightly more accurate in identifying patients at low risk than the CURB-65 score.

Differentiation of bacterial and non-bacterial community-acquired pneumonia by thin-section computed tomography.

BACKGROUND AND OBJECTIVE: The management of community-acquired pneumonia (CAP) depends, in part, on the identification of the causative agents. The objective of this study was to determine the potential of thin-section computed tomography (CT) in differentiating bacterial and non-bacterial pneumonia. PATIENTS AND METHODS: Thin-section CT studies were prospectively examined in hospitalized CAP patients within 2 days of admission, followed by retrospective assessment by two pulmonary radiologists. Thin-section CT findings on the pneumonias caused by each pathogen were examined, and two types of pneumonias were compared. Using multivariate logistic regression analyses, receiver operating characteristic (ROC) curves were produced. RESULTS: Among 183 CAP episodes (181 patients, 125 men and 56 women, mean age+/-S.D.: 61.1+/-19.7) examined by thin-section CT, the etiologies of 125 were confirmed (94 bacterial pneumonia and 31 non-bacterial pneumonia). Centrilobular nodules were specific for non-bacterial pneumonia and airspace nodules were specific for bacterial pneumonia (specificities of 89% and 94%, respectively) when located in the outer lung areas. When centrilobular nodules were the principal finding, they were specific but lacked sensitivity for non-bacterial pneumonia (specificity 98% and sensitivity 23%). To distinguish the two types of pneumonias, centrilobular nodules, airspace nodules and lobular shadows were found to be important by multivariate analyses. ROC curve analysis discriminated bacterial pneumonia from non-bacterial pneumonia among patients without underlying lung diseases, yielding an optimal point with sensitivity and specificity of 86% and 79%, respectively, but was less effective when all patients were analyzed together (70% and 84%, respectively). CONCLUSION: Thin-section CT examination was applied for the differentiation of bacterial and non-bacterial pneumonias. Though showing some potential, this examination at the present time would not be applicable for patients with underlying lung diseases, severe conditions of pneumonia, or immunocompromised conditions.