Management Of Severe Community-acquired Pneumonia Research Articles

Advancements in the Management of Severe Community-Acquired Pneumonia: A Comprehensive Narrative Review.

Pneumonia, classified as a lower respiratory tract illness, affects different parts of the bronchial system as well as alveoli and can present with varying severities depending on co-morbidities and causative pathogens. It can be broadly classified using the setting in which it was acquired, namely the community or hospital setting, the former being more common and spreading through person-to-person droplet transmission. Community-acquired pneumonia (CAP) is currently the fourthleading cause of death worldwide, and its high mortality makes continual insight into the management of the condition worthwhile. This review explores the literature specifically for severe CAP (sCAP) and delves into the diagnosis, various modalities of treatment, and management of the condition. This condition can be defined as pneumonia requiring mechanical ventilation in the ICU and/or presenting with sepsis and organ failure due to pneumonia. The disease process is characterized by inflammation of the lung parenchyma, initiated by a combination of pathogens and lowered local defenses. Acute diagnosis of the condition is vital in reducing negative patient outcomes, namely through clinical presentation, blood/sputum cultures, imaging modalities such as computed tomography scan, and inflammatory markers, identifying common causative pathogens such as Streptococcuspneumoniae, rhinovirus, Legionella, and viral influenza. Pathogens such as Escherichia colishould also be investigated in patients with chronic obstructive pulmonary disease. The mainstay of treating sCAP includes rapid ICU admission once a diagnosis has been confirmed, initiating sepsis protocol, and treatment with combined empiric antibiotic regimens consisting of beta-lactams and macrolides. Corticosteroid use alongside antibiotics shows promise in reducing inflammation, but its use has to be judged on a case-by-case basis. New drugs such as omadacycline, delafloxacin, and zabofloxacin have shown valid evidence for the treatment of resistant causative organisms. The main guidelines for preventing sCAP include maintaining a healthy lifestyle, and annual pneumococcal and influenza vaccines are recommended for the most vulnerable patient groups, such as those with COPD and immunosuppression.

Severe community-acquired pneumonia: principles of diagnostics and intensive therapy

BACKGROUND. Pneumonia is an important medical and social problem due to its high prevalence, high rates of disability and mortality, and significant economic losses due to this disease. In Ukraine in 2017, the incidence of pneumonia among adults was 384.0 cases per 100,000 population, and the mortality rate was 11.7 per 100,000 population, i. e. more than 3 % of those who had pneumonia died. Community-acquired pneumonia (CAP) is the leading cause of morbidity and mortality from pneumonia among all age groups worldwide: 3-4 million people suffer from CAP with high morbidity and mortality.
 OBJECTIVE. To analyze the pathogenesis, diagnosis, and treatment of severe CAP from the modern literature data to optimize the treatment of this group of patients.
 MATERIALS AND METHODS. Bibliosemantic, comparative, and system analysis methods were used. The proposed recommendations are based on the analysis of modern literature, the results of randomized studies, and meta-analyses devoted to the investigation of the problem of diagnosis and management of severe CAP.
 RESULTS AND DISCUSSION. The problems of pathogenesis, diagnosis, and treatment of severe CAP were analyzed using modern literature data to optimize the treatment of this group of patients. CAP can be caused by various pathogens, such as Streptococcus pneumoniae, Haemophilus influenzae, atypical bacteria (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella species), and viruses. It is quite difficult to establish the etiology of pneumonia even with the use of modern microbiological technologies, therefore, in many countries of the world, a classification is used that takes into account the conditions of the occurrence of the disease, the features of the infection of the lung tissue, as well as the immune reactivity of the patient’s organism. This classification makes it possible to predict the probable causative agent of the disease with a fairly high degree of probability. The diagnosis of CAP is considered established in the presence of radiologically confirmed focal infiltration of lung tissue and at least two of the following clinical signs: acute onset of the disease with a body temperature >38 °C, cough with sputum, physical signs (muffled or dull percussion sound, weakened and/or harsh bronchial breathing, a focus of sonorous small vesicular rales and/or crepitations), leukocytosis (>10×109 /L), and/or shift to rod nuclear cells (>10 % of them). The severity of CAP is assessed clinically, as well as using the criteria given in the scales to determine the need for the patient to be hospitalized or admitted to the intensive care unit (ICU). Patients with CAP requiring mechanical ventilation or with septic shock should be admitted to the ICU.
 CONCLUSIONS. Severe CAP is associated with high morbidity and mortality, and although there are European and non-European guidelines for CAP, there are no specific guidelines for severe CAP. These international guidelines from ERS, ESICM, ESCMID, and ALAT present evidence-based clinical recommendations for the diagnosis, empiric treatment, and antibiotic therapy of severe CAP according to the GRADE approach. In addition, existing knowledge gaps were identified and recommendations for future research were provided.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia

Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. In these international guidelines, ERS, ESICM, ESCMID and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Value of syndromic panels in the management of severe community-acquired pneumonia.

Community-acquired pneumonia requiring hospital admission is a prevalent and potentially serious infection, especially in high-risk patients (e.g., those requiring ICU admission or immunocompromised). International guidelines recommend early aetiological diagnosis to improve prognosis and reduce mortality. Syndromic panels that detect causative pathogens by molecular methods are here to stay. They are highly sensitive and specific for detecting the targets included in the test. A growing number of studies measuring their clinical impact have observed increased treatment appropriateness and decreased turnaround time to aetiological diagnosis, need for admission, length of hospital stay, days of isolation, adverse effects of medication and hospital costs. Its use is recommended a) per a pre-established protocol on making the diagnosis and managing the patient, b) together with an antimicrobial stewardship programme involving both the Microbiology Service and the clinicians responsible for the patient, and c) the final evaluation of the whole process. However, we recall that microbiological diagnosis with traditional methods remains mandatory due to the possibility that the aetiological agent is not included among the molecular targets and to determine the antimicrobial susceptibility of the pathogens detected.

Metagenomic Next-Generation Sequencing for Pathogenic Diagnosis and Antibiotic Management of Severe Community-Acquired Pneumonia in Immunocompromised Adults.

BackgroundMetagenomic next-generation sequencing (mNGS) is a promising technique for pathogens diagnosis. However, application of mNGS in immunocompromised adults with severe community-acquired pneumonia (SCAP) is relatively limited.MethodsWe retrospectively reviewed 23 immunocompromised and 21 immunocompetent SCAP patients with mNGS detection from April 2019 to December 2019. The performances of pathogenic diagnosis and subsequently antibiotic adjustment in immunocompromised SCAP patients were compared to immunocompetent SCAP patients. The defined by days of therapy (DOT) method was used for estimate daily antibiotic use.ResultsThere was a significant difference in the diagnostic positivity rate between mNGS and conventional test in both groups (P<0.001). Compared to immunocompetent patients, more mixed pathogens in immunocompromised patients were found (P=0.023). Before the availability of mNGS, the DOTs in immunocompromise patients were higher than immunocompetent patients (3.0 [3.0, 4.0] vs. 3.0 [2.0, 3.0], P=0.013). Compared to immunocompetent patients, immunocompromised patients had fewer full pathogen covered empirical antibiotic therapy (14.7% vs. 57.1%, P=0.022), more adjustments of antibiotic treatment (87.0%) vs. 57.1%, P=0.027). More than a half (13 of 23) SCAP patients in immunosuppressed group had reduced or downgraded antibiotic adjustments based on the results.ConclusionsmNGS may be a useful technique for detecting mixed pathogens and personalized antibiotic treatment in immunocompromised SCAP patients.

Could Respiratory Fluoroquinolones, Levofloxacin and Moxifloxacin, Prove to be Beneficial as an Adjunct Treatment in COVID-19?

Since the beginning of the COVID-19 pandemic, researchers have focused on repurposing of existing antibiotics, antivirals and anti-inflammatory drugs to find an effective therapy. Fluoroquinolones are broad spectrum synthetic antimicrobial agents, being chemical derivatives of quinoline, the prodrome of chloroquine. Interestingly, fluoroquinolones may exert antiviral actions against vaccinia virus, papovavirus, CMV, VZV, HSV-1, HSV-2, HCV and HIV. A recent in silico study has shown that the fluoroquinolones, ciprofloxacin and moxifloxacin, may inhibit SARS-CoV-2 replication by exhibiting stronger capacity for binding to its main protease than chloroquine and nelfinavir, a protease inhibitor antiretroviral drug. Remarkably, fluoroquinolones have shown multiple immunomodulatory actions leading to an attenuation of the inflammatory response through the inhibition of pro-inflammatory cytokines. Noteworthy, respiratory fluoroquinolones, levofloxacin and moxifloxacin, constitute fist line therapeutic agents for the management of severe community-acquired pneumonia. They are characterized by advantageous pharmacokinetic properties; higher concentrations in the lungs; and an excellent safety profile comparable to other antibiotics used to treat respiratory infections, such as macrolides and b-lactams. Based on their potential antiviral activity and immunomodulatory properties, the favorable pharmacokinetics and safety profile, we propose the use of respiratory fluoroquinolones as adjuncts in the treatment of SARS-CoV-2 associated pneumonia.

Blind Spots of Traditional Microbiological Tests for Severe Community-Acquired Pneumonia in Adults and Availability of Nonculture Techniques: A Nationwide Survey of Physicians in China

In China, no national survey has been conducted to evaluate physicians' attitudes and compliance with guidelines in the management of adult patients with community-acquired pneumonia (CAP). Therefore, this study aimed to evaluate physicians' awareness of the use of microbiological tests in the management of severe CAP (SCAP) and to investigate the availability of nonculture tests in China. A nationwide electronic questionnaire survey was conducted among Chinese physicians between March and July 2018, which assessed their viewpoints concerning the issues in the management of SCAP. A total of 6333 physicians completed this survey, evenly covering all career stages. Among these, 3208 (50.6%) and 1936 (30.6%) had blind spots in the application of blood and sputum cultures in the management of SCAP, respectively. Nonteaching hospital, nonrespirologists, and junior career stage were independently associated with misunderstandings. Regarding nonculture methods, 52.7% of the facilities had no access to polymerase chain reaction-based pathogen detection tests. The accessibility of urinary antigen tests for Streptococcus pneumoniae (42.5%) and Legionella pneumophila (38.5%) was also low. The main barriers were inland and remote region, lower hospital level, and nonteaching hospital. Insufficient use of sputum and blood cultures, together with low accessibility of major nonculture techniques, were noticeable barriers to achieving microbiological diagnosis of SCAP in China. To help curb the overuse of broad-spectrum antibiotics, further measures should be taken to raise awareness among nonspecialists and promote rapid nonculture tests, especially in nonteaching hospitals and developing regions.

Effect of low-dose systemic steroid therapy on the management of severe community-acquired pneumonia

Introduction The rationale behind the study is that as severe pneumonia is associated with local and systemic inflammatory response, the systemic steroid with its anti-inflammatory effect may affect the outcome and prognosis in severe pneumonia. Objective The aim was to assess the effect of systemic steroid on the course and outcomes of severe community-acquired pneumonia (CAP). Patients and methods This study was a prospective, randomized, controlled study conducted on 60 patients, hospitalized with severe CAP. The patients were divided into two groups: a case group undergone usual antibiotic regimen for CAP according to the guidelines plus systemic steroid therapy with prednisolone 0.5 mg/kg daily for 1 week and a control group without any systemic steroids. The primary outcome was the treatment success and duration of hospitalization. Results The treatment was more successful in the case group compared with the control group (93.3 vs. 70.0%, respectively) with statistically significant difference. The mean days of hospitalization, the mean levels of C-reactive protein after treatment, and the mean decline of C-reactive protein levels were significantly lower among the case group. However, there was no significant difference between the two groups as regards mortality. Conclusion Low-dose systemic steroids significantly increase the success of treatment in severe CAP with less days of hospitalization.

Management of severe community acquired pneumonia in the emergency department

Severe community acquired pneumonia (CAP) is a medical emergency and thus, it should be managed as such. Prompt recognition of severe CAP and timely, appropriate initiation of antimicrobials and execution of resuscitation bundles in the emergency department (ED) will save lives and reduce the burden of disease in hospital and patient morbidities downstream. However, these are complex multifaceted interventions which require deliberate planning and design, careful implementation sustained by close monitoring and maintenance efforts. Widespread implementation of these measures is further hampered by uncertainties, controversies and debates between researchers on the evidential basis for the precise strati cation of CAP disease severity and the relative merits of different treatment options. Physicians in the ED however should not hesitate to act but apply the best available evidence in the local settings heuristically with pragmatic interventions to improve critical outcomes for patients with severe CAP. In this regard, we have performed a qualitative, aggregative type review of the management of severe CAP in the ED concluding each section with a realist synthesis. We describe the implementation of resuscitation bundles in the management of severe CAP in the ED and the process of sustaining such an enterprise.

Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study

Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established.To evaluate the impact of different aspects of AT on the outcome of critically ill patients with CAP, we performed a post hoc analysis of all CAP patients enrolled in a prospective, observational, multicentre study.Of the 502 patients included, 76% received combination therapy, mainly a β-lactam with a macrolide (80%). AT was inappropriate in 16% of all microbiologically documented CAP (n=177). Hospital and 6months mortality were 34% and 35%. In adjusted multivariate logistic regression analysis, combination AT with a macrolide was independently associated with a reduction in hospital (OR 0.17, 95%CI 0.06–0.51) and 6months (OR 0.21, 95%CI 0.07–0.57) mortality. Prolonged AT (>7days) was associated with a longer ICU (14 vs. 7days; p<0.001) and hospital length of stay (LOS) (25 vs. 17days; p<0.001).Combination AT with a macrolide may be the most suitable AT strategy to improve both short and long term outcome of severe CAP patients. AT >7days had no survival benefit and was associated with a longer LOS.

What We Learned From the EU-VAP/CAP Study for Severe Pneumonia

EU-VAP/CAP is the largest observational, multicenter, international study conducted in Europe, focusing on severe pneumonia in the intensive care unit. It provided important insights into the different aspects of diagnostics and management of severe community-acquired pneumonia (CAP) and nosocomial pneumonia. Incidence, specificities of early-onset and late-onset settings, microbiologic etiology, antimicrobial prescription, and outcomes were analyzed, with a closer look at ventilator-associated pneumonia (VAP). Distinct populations showing specific risk factors, and outcomes were set (trauma VAP, elderly VAP, chronic obstructive pulmonary disease VAP), stressing VAP variety and complexity. This review assesses EU-VAP/CAP findings that opened perspectives on future research: the role of antibiotic choice in reducing severe CAP mortality, the study of a very early-onset VAP subset, the high frequency of potential resistant microorganisms in VAPs without known risk factor for resistance, the importance of describing specific VAP subpopulations (trauma, elderly, chronic obstructive pulmonary disease), and the insufficiency of nurse-to-patient ratio index to assess the nursing impact on VAP occurrence. The EU-VAP/CAP study comprehensively helped portray the picture of severe pneumonia across Europe and clarify the main themes that need to be scrutinized in the near future to reduce the heavy burden of severe CAP and VAP.

Management of severe community-acquired pneumonia in Brazil: a secondary analysis of an international survey

ObjectiveThis study aimed to evaluate Brazilian physicians’ perceptions regarding the diagnosis, severity assessment, treatment and risk stratification of severe community-acquired pneumonia patients and to compare those perceptions to current guidelines.MethodsWe conducted a cross-sectional international anonymous survey among a convenience sample of critical care, pulmonary, emergency and internal medicine physicians from Brazil between October and December 2008. The electronic survey evaluated physicians’ attitudes towards the diagnosis, risk assessment and therapeutic interventions for patients with severe community-acquired pneumonia.ResultsA total of 253 physicians responded to the survey, with 66% from Southeast Brazil. The majority (60%) of the responding physicians had > 10 years of medical experience. The risk assessment of severe community-acquired pneumonia was very heterogeneous, with clinical evaluation as the most frequent approach. Although blood cultures were recognized as exhibiting a poor diagnostic performance, these cultures were performed by 75% of respondents. In contrast, the presence of urinary pneumococcal and Legionella antigens was evaluated by less than 1/3 of physicians. The vast majority of physicians (95%) prescribe antibiotics according to a guideline, with the combination of a 3rd/4th generation cephalosporin plus a macrolide as the most frequent choice.ConclusionThis Brazilian survey identified an important gap between guidelines and clinical practice and recommends the institution of educational programs that implement evidence-based strategies for the management of severe community-acquired pneumonia.

Management of severe community-acquired pneumonia: A survey on the attitudes of 468 physicians in Iberia and South America

PurposeThe purpose of this study is to characterize the practices of pulmonary, internal medicine, and critical care physicians toward the management of patients with severe community-acquired pneumonia (CAP). Materials and methodsA cross-sectional international anonymous survey was conducted among a convenience sample of critical care, pulmonary, emergency, and internal medicine physicians from Portugal, Spain, and South America between October and December 2008. The electronic survey evaluated physicians’ attitudes toward diagnosis, risk assessment, and therapeutic interventions for patients with severe CAP. ResultsFour hundred sixty-eight physicians responded being 84.6% from 4 countries (Brazil, Portugal, Spain, and Argentina) whom 66.9% had more than 10 years experience. Risk assessment of severe CAP was very heterogeneous being clinical evaluation the most frequent. Although blood cultures were recognized as presenting a poor diagnostic performance, they were performed by 77.1%. In opposition, the presence of urinary pneumococcal and Legionella antigen was asked by less than one-third of physicians. The great majority (95%) prescribes antibiotics according to a guideline being the combination of β-lactam plus macrolide the most frequent choice. ConclusionsDespite the recent advances of knowledge reflected in the present study in the management of severe CAP, several of them are still incompletely translated into clinical practice. Significant variation in practice is observed among physicians and represents a potential target for future research and educational interventions.

Adjunctive Therapy in Community-Acquired Pneumonia

Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the eighth overall leading cause of death in the United States. For this reason, adjunctive therapeutic measures directed at the host response rather than the pathogen are attractive. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. The existing literature does not demonstrate a clear benefit for corticosteroids, but larger prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome positively. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, but neither drotrecogin alfa activated nor tifacogin (recombinant tissue factor pathway inhibitor) have demonstrated a survival benefit. Other therapies have theoretical benefit but are not yet in the stage of clinical trials.

Adjunctive Therapy in Community-Acquired Pneumonia

Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the seventh overall leading cause of death in the United States. For this reason, interest has been redirected into non-antibiotic therapeutic measures. Despite theoretical benefits, the existing literature does not suggest a clear benefit for corticosteroid treatment, but large prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, possibly even more so than for sepsis in general. The CAP subgroup in phase III sepsis trials of both drotrecogin alfa (activated) and tifacogin (recombinant tissue factor pathway inhibitor) demonstrated the greatest benefit. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. Exogenous surfactant replacement is being explored as adjunctive therapy for acute lung injury due to CAP. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome. Other therapies have theoretical benefit but are not yet in the stage of clinical trials.