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Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs.

Rationale: In 2017, the International European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thora...

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., For patients with acute COVID-19 pneumonia who require oxygen support, the International Task Force made suggestions for remdesivir and dexamethasone, but against hydroxychloroquine. Post-discharge management of COVID-19 survivors is a research priority. https://bit.ly/32B96uI

Objectives Community-acquired pneumonia (CAP) is an important complication in patients with chronic obstructive pulmonary disease (COPD). This study aimed to define incidence, and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, and to estimate the burden of disease in the US population. Methods This was a secondary analysis of a prospective population-based cohort study of residents in Louisville, Kentucky, 40 years old and older, from 1 June 2014 to 31 May 2016. All adults hospitalized with CAP were enrolled. The annual incidence of pneumonia in COPD patients in Louisville was calculated and the total number of adults with COPD hospitalized in the United States was estimated. Clinical outcomes included time to clinical stability (TCS), length of hospital stay (LOS) and mortality. Results From a Louisville population of 18 246 patients with COPD, 3419 pneumonia hospitalizations were documented during the 2-year study. The annual incidence was 9369 patients with pneumonia per 100 000 COPD population, corresponding to an estimated 506 953 adults with COPD hospitalized due to pneumonia in the United States. The incidence of CAP in patients without COPD was 509 (95% CI 485–533) per 100 000. COPD patients had a median (interquartile range) TCS and LOS of 2 (1–4) and 5 (3–9) days respectively. The mortality of COPD patients during hospitalization, at 30 days, 6 months and 1 year was 193 of 3419 (5.6%), 400 of 3374 (11.9%), 816 of 3363 (24.3%) and 1104 of 3349 (33.0%), respectively. Conclusions There was an annual incidence of 9369 cases of hospitalized CAP per 100 000 COPD patients in the city of Louisville. This was an approximately 18-fold greater incidence of CAP in COPD patients than in those without COPD.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents.

Introduction The efficacy and safety of telavancin versus vancomycin in microbiologically evaluable patients with hospital-acquired or ventilator-associated pneumonia (HAP/VAP) caused by Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥ 1.0 µg/mL was analyzed using data derived from previously reported Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) trials. Methods This post hoc subgroup analysis of two randomized, double-blind, comparator-controlled, parallel-group phase 3 trials conducted at 274 sites in 38 countries included 194 microbiologically evaluable patients with HAP/VAP caused by monomicrobial S. aureus with vancomycin MIC ≥ 1.0 µg/mL. Patients received intravenous telavancin (10 mg/kg every 24 h) or intravenous vancomycin (1 g every 12 h with site-specific modifications) for 7–21 days. Efficacy was assessed by clinical cure, defined as improvement or non-progression of radiographic findings at end of treatment and resolution of pneumonia signs and symptoms at follow-up/test-of-cure visits, and survival 28 days post-randomization. Safety was assessed from categorical shifts in creatinine clearance during therapy and adverse events (AEs). Results Clinical cure rates were numerically greater following telavancin versus vancomycin treatment overall (85.4% vs. 74.3%; treatment difference [95% confidence interval (CI)], 11.1% [− 0.002%, 22.2%]) and in patients aged ≥ 65 years (81.6% vs. 66.2%; treatment difference [95% CI], 15.5% [− 0.9%, 30.2%]) patients with VAP (92.3% vs. 47.6%; treatment difference [95% CI], 44.7% [18.1%, 64.9%]), and patients with baseline Acute Physiology And Chronic Health Evaluation II score ≥ 20 (71.4% vs. 55.6%; treatment difference [95% CI], 15.9% [− 11.7%, 40.5%]). Renal function declined in 7 (7.9%) patients receiving telavancin and 6 (5.7%) patients receiving vancomycin. Survival proportion was numerically higher (85.2% vs. 80.2%; treatment difference [95% CI], 5.0% [− 5.8%, 15.8%]) and AEs were comparable in patients treated with telavancin versus vancomycin. Conclusion Telavancin is an alternative to vancomycin for HAP/VAP caused by S. aureus with vancomycin MIC ≥ 1 µg/mL. Funding Theravance Biopharma R&D, Inc., South San Francisco, CA, USA.

Introduction: Routine pneumococcal vaccination for adults aged ≥60 or ≥65 years and those with underlying at-risk and high-risk conditions is recommended in many countries. However, studies estimating the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) have revealed mixed results, explained, in part, by variability in study design and endpoints used to assess outcomes.Areas covered: The authors conducted a literature review of independently randomized trials and real-world studies published from 2010-2020 that assessed the effectiveness and efficacy of PPSV23 against vaccine-type or any-serotype invasive and non-invasive pneumococcal disease in adults aged ≥60 years. The authors also evaluated differences in study design that may contribute to the heterogeneity of available evidence.Expert opinion: Policy decisions regarding the inclusion of vaccines into national immunization plans should be made taking the quality and limitations of studies into account. This review shows that PPSV23 is effective against vaccine-type invasive pneumococcal disease and vaccine-type pneumococcal pneumonia. It can also lower the burden of vaccine-type pneumococcal pneumonia. PPSV23-conferred protection may be lower in adults aged ≥75 years, those with certain underlying conditions, and individuals who were vaccinated >5 years before disease onset. This is an important finding that supports the benefit of PPSV23 vaccination for older adults.

While the world is grappling with the consequences of a global pandemic related to SARS-CoV-2 causing severe pneumonia, available evidence points to bacterial infection with Streptococcus pneumoniae as the most common cause of severe community acquired pneumonia (SCAP). Rapid diagnostics and molecular testing have improved the identification of co-existent pathogens. However, mortality in patients admitted to ICU remains staggeringly high. The American Thoracic Society and Infectious Diseases Society of America have updated CAP guidelines to help streamline disease management. The common theme is use of timely, appropriate and adequate antibiotic coverage to decrease mortality and avoid drug resistance. Novel antibiotics have been studied for CAP and extend the choice of therapy, particularly for those who are intolerant of, or not responding to standard treatment, including those who harbor drug resistant pathogens. In this review, we focus on the risk factors, microbiology, site of care decisions and treatment of patients with SCAP.

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Pneumonia is a common problem in the elderly with higher short- and long-term mortality than younger patients and similar age patients with other illnesses. Aggressive care may not be justified and broad-spectrum antibiotics may create antibiotic resistant pathogens that harm others.http://bit.ly/2P8LUNp

Hospital-acquired pneumonia (HAP) is a form of nosocomial pneumonia, distinct from ventilator-associated pneumonia (VAP). This review compares HAP and VAP, highlighting differences in natural history, risk factors, and bacteriology that necessitate a different approach to the therapy of HAP, compared with VAP.HAP can arise out of the ICU, or in the ICU, and can lead to severe illness, including the need for intubation and mechanical ventilation. New American and European nosocomial pneumonia guidelines make therapy recommendations for HAP. The American guidelines recommend broader spectrum therapy than the European guidelines, but recent studies support the idea that not all HAP patients need antipseudomonal therapy. When the American guideline approach to HAP has been studied, it led to both overtreatment and inappropriate therapy for the identified pathogens. An algorithm, modified from the European guideline, proposes an approach to therapy that necessitates dual antipseudomonal therapy in less than 25% of all HAP patients.Although more prospective therapy trials of HAP are needed, based on currently available data, it is possible to use an approach that provides appropriate therapy without the overuse of broad-spectrum therapy.

Summary A subgroup of patients admitted to the hospital with a diagnosis of community-acquired pneumonia (CAP) have received antibiotic therapy prior to admission for the current episode of pneumonia. The objective of this study was to assess the clinical course of patients receiving antibiotics prior to admission, compared to patients not previously treated. An observational cohort of 3364 CAP patients consecutively admitted to our hospital, and prospectively included, were studied. We collected clinical, microbiological and biochemical parameters, focusing on recent antibiotics received prior to admission. 610 (18%) patients received antibiotics prior to hospital admission for the current CAP episode. Patients with previous antibiotic use developed septic shock less frequently (4% vs. 7%, p = 0.007) and required invasive ventilation less often (3% vs. 6%, p = 0.002). After adjustment by different covariate factors and propensity score, antibiotic therapy was still independently associated with a lower incidence of septic shock at admission (OR 0.54 [95% CI 0.31–0.95], p = 0.03) and less need for invasive ventilation (OR 0.38 [95% CI 0.16–0.91], p = 0.03). In this cohort, recent use of antibiotics before hospital admission in CAP seems to be associated with a lower incidence of septic shock on admission and a lower need for invasive ventilation.

BACKGROUND: The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) Community-acquired Pneumonia (CAP) guidelines were developed using systematic reviews to inform every recommendation, as suggested by the Institute of Medicine Standards for Trustworthy Guidelines. Recent studies suggest that an expert consensus-based approach, called the Convergence of Opinion on Recommendations and Evidence (CORE) process, can produce recommendations that are concordant with recommendations informed by systematic reviews. PURPOSE: The goal of the study was to evaluate the efficacy of the CORE process had it been used to develop the ATS/IDSA CAP guidelines. METHODS: Experts in CAP who were not on the guideline panel and had no knowledge of the guideline’s systematic reviews or recommendations were recruited to participate in the CORE process, addressing the same questions asked by the guideline panel. Recommendations derived from the CORE process were compared to the guideline recommendations. Concordance of the course of action, strength of recommendation, and quality of evidence were determined. RESULTS: Using a threshold of 70% of experts selecting the same course of action to make a recommendation, the CORE process yielded a recommendation for 20 of 31 (65%) questions. Among the 20 CORE-derived recommendations, 19 (95%) were concordant with the guideline recommendations (kappa agreement 0.88, 95% CI .64–1.00). There was less agreement among the strength of recommendations (58%) and quality of evidence (42%). CONCLUSIONS: If the CORE process had been used, 11 systematic reviews would have been necessary rather than 31, with minimal impact on the recommended courses of action.

We aimed to assess the predictive performance of risk factors for multi drug resistant pathogens (MDRP) as defined by the International ERS/ESICM/ESCMID/ALAT guidelines in 2017. Adults admitted between 2004 and 2017 in six ICUs of the Hospital Clinic of Barcelona with a diagnosis of nosocomial pneumonia microbiologically confirmed were enrolled. Among 314 patients included in the study, 312 were at high MDR risk: 158 (51%) had no septic shock (group 1) and 154 (49%) had septic shock (group 2). Despite no difference in the microbiology, at pneumonia diagnosis, compared to group 1, patients in group 2 presented a higher SOFA (9 [8;12] vs. 5 [4;7] p 0.6. Previous isolation of MDRP showed the best performance for MDR prediction.

Although analysis of retrospective studies has documented survival benefit from the addition of a macrolide to the treatment regimen for community-acquired pneumonia (CAP), no data are available to determine if there is differential efficacy between members of the macrolide family. In order to investigate this, an analysis was undertaken of data from 1174 patients with CAP who met the new Sepsis-3 definitions and were enrolled prospectively in the data registry of the Hellenic Sepsis Study Group. Four well-matched treatment groups were identified with 130 patients per group: clarithromycin and β-lactam; azithromycin and β-lactam; respiratory fluoroquinolone and β-lactam monotherapy. The primary endpoint was comparison of the effects of clarithromycin with β-lactam monotherapy on 28-day mortality. The secondary endpoint was resolution of CAP. Mortality rates for the clarithromycin, azithromycin, respiratory fluoroquinolone and β-lactam groups were 20.8%, 33.8% (P=0.026 vs clarithromycin), 32.3% (P=0.049 vs clarithromycin) and 36.2% (P=0.009 vs clarithromycin), respectively. After stepwise Cox regression analysis among all groups, clarithromycin was the only treatment modality associated with a favourable outcome (hazard ratio 0.61; P=0.021). CAP resolved in 73.1%, 65.9% (P=0.226 vs clarithromycin), 58.5% (P=0.009 vs clarithromycin) and 61.5% (P=0.046 vs clarithromycin) of patients, respectively. It is concluded that the addition of clarithromycin to the treatment regimen of patients with severe CAP leads to better survival rates.

Background Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL). Methods We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause. Results Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies. Conclusions The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis.

SCOPUS: le.j, info:eu-repo/semantics/published

Purpose of review Community-acquired pneumonia (CAP) is a pervasive disease that is encountered in outpatient and inpatient settings. CAP is the leading cause of death from an infectious disease and accounts for significant worldwide morbidity and mortality. This update reviews current advances that can be used to promote improved outcomes in CAP. Recent findings Early recognition of CAP and its severe presentations, with appropriate site of care decisions, leads to reduced patient mortality. In addition to traditional prognostic tools, certain serum biomarkers can assist in defining disease severity and guide treatment and management strategies. The use of macrolides as part of combination antibiotic therapy has shown beneficial mortality effects across the CAP disease spectrum, especially for those with severe illness. When treating community-associated, methicillin-resistant Staphylococcus aureus pneumonia, use of an antitoxin antibiotic is likely to be valuable. Adjunctive therapy with corticosteroids may prevent delayed clinical resolution in selected patients with severe CAP. Recent data expand on the interaction of CAP with comorbid disease, particularly cardiovascular disease, and its impact on mortality in CAP patients. Summary Improved diagnostic tools, optimized treatment regimens, and enhanced understanding of CAP-induced perturbations in comorbid disease states hold promise to improve patient outcomes.

Bilateral but not unilateral multilobar pneumonia is an independent risk factor for mortality in CAPhttp://ow.ly/ZNLD4

Background In Japan, the routine use of early antiviral therapy for patients with influenza is standard. Methods This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy. Results Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza. Conclusions Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza. Trial Registry Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/

The current rates of ventilator-associated pneumonia (VAP) are falling, in large part, as a result of effective prevention strategies. However, the application and efficacy of VAP prevention is being challenged by efforts to replace VAP surveillance with monitoring for ventilator-associated complications (VAC), which include many non-infectious processes. VAP prevention is based on interrupting pneumonia pathogenesis by avoiding the inoculation of contaminated oral secretions into the lower respiratory tract. This starts by using non-invasive ventilation in place of endotracheal intubation whenever possible, placing all tracheal and gastric tubes through the mouth and not the nose, and making daily efforts to liberate patients from mechanical ventilation. Intervention strategies to avoid microaspiration of oral contents to the lung have focused on the use of modified respiratory therapy equipment. This includes endotracheal tubes with subglottic secretion drainage channels, endotracheal tube cuffs made of special materials and of special shape, adaptation of endotracheal tube materials to prevent the development of biofilm, cleaning tubes with biofilm removal devices, and using devices to maintain endotracheal tube cuff pressure. Decontamination of oral secretions with chlorhexidine is commonly incorporated, as part of routine oral care, in many patients. The use of 24 h of prophylactic antibiotics after emergent intubation is also a valuable strategy, but controversy about selective digestive and selective oral decontamination persists, because of concerns about the emergence of antibiotic resistance, particularly in ICUs with high baseline rates of resistance. Other interventions are of less certain benefit, such as post-pyloric feeding, elevation of the head of the bed, and use of probiotics. This review makes recommendations about which current prevention strategies have the greatest potential to reduce the frequency of VAP.

Purpose Severe community-acquired pneumonia (SCAP) is still associated with substantial morbidity and mortality. In this point-of-view review paper, a group of experts discuss the main controversies in SCAP: the role of severity scores to guide patient settings of care and empiric antibiotic therapy; the emergence of pathogens outside the core microorganisms of CAP; viral SCAP; the best empirical treatment; septic shock as the most lethal complication; and the need for new antibiotics. Methods For all topics, the authors describe current controversies and evidence and provide recommendations and suggestions for future research. Evidence was based on meta-analyses, most recent RCTs and recent interventional or observational studies. Recommendations were reached by consensus of all the authors. Results and conclusions The IDSA/ATS criteria remain the most pragmatic tool to predict ICU admission. The authors recommend a combination of a beta-lactam/beta-lactamase inhibitor or a third G cephalosporin plus a macrolide in most SCAP patients, and to empirically cover PES (P. aeruginosa, extended spectrum beta-lactamase producing Enterobacteriaceae, methicillin-resistant S. aureus) pathogens when at least two specific risk factors are present. In patients with influenza CAP, the authors recommend the use of oseltamivir and avoidance of the use of steroids. Corticosteroids can be used in case of refractory shock and high systemic inflammatory response.

BACKGROUND Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition. METHODS We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP). RESULTS Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit

Background Streptococcus pneumoniae (SP) is one of the most common pathogens of Community-Acquired Pneumonia (CAP), but recent reports suggest that its incidence may be declining in relation to the use of the conjugate 13-valent pneumococcal vaccine in children. We compared the result of the immunochromatographic SP urinary antigen test (SPUAT) and clinical outcomes in patients with CAP admitted in two periods of time: 2001–2002(CAP1) and 2015–2016(CAP2). Methods This was a matched nested case-control study of two prospectively recorded cohorts of patients admitted with CAP, with SPUAT and blood culture performed in all patients. CAP2 cases and CAP1 controls were matched for age ± 4 years, sex, and Pneumonia Severity Index (PSI) score ± 10 points. Odds ratios (OR) for having SPUAT positive was estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables. Results Four hundred ninety-eight patients were recruited; 307 during the CAP1 and 191 during the CAP2 periods. Comparing both periods we observed differences, in age, PSI score, and the percentage of smokers, outpatients, previously immunized with pneumococcal vaccine, and positive SPUAT. On the other hand, mortality, admission from nursing homes, pneumococcal bacteremia and hospital admission were not different. After matching, pneumonia due to SP per the SPUAT was observed in 34(23.4%) of CAP1 and in 12(8.3%) of CAP2 patients (p

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empirical treatment, response to treatment, new antibiotics or new forms of antibiotic administration, and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society (ERS) launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), were invited to participate and appointed their representatives. The Latin American Society of Thoracic Diseases (ALAT) was also invited to participate. This manuscript summarises the evidence and recommendations of these international guidelines on HAP and VAP., A summary of the evidence and recommendations made in the ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia http://ow.ly/S3zA30iZfLa

Background Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial. Methods We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL) who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone) and corticosteroid arm (placebo or corticosteroids). The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure). Results The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI) risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374); however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31%) vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24%) vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0%) vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009). We found a significant difference for In-hospital mortality in the per protocol population (overall p = 0.01). We did not find significant differences in treatment failure, early or late; or In-hospital mortality after adjusting for severity (PSI), year and centre of enrolment. Conclusions In this exploratory analysis, we observed that the glucocorticosteroids and macrolides combination had no statistically significant association with main clinical outcomes compared with other combinations in patients with severe community acquired pneumonia and a high inflammatory response after taking account potential confounders. Trial registration Clinicaltrials.gov NCT00908713.

Objective To define clinical features associated with Intensive Care Unit (ICU) infections caused by multi-drug resistant organisms (MDRO) and their impact on patient outcome. Design A single-center, retrospective case–control study was carried out between January 2010 and May 2010. Setting A medical ICU (MICU) in the United States. Patients The study included a total of 127 MDRO-positive patients and 186 MDRO-negative patients. Interventions No interventions were carried out. Results Out of a total of 313 patients, MDROs were present in 127 (41.7%). Based on the multivariate analysis, only infection as a cause of admission [OR 3.3 (1.9–5.8)]), total days of ventilation [OR 1.07 (1.01–1.12)], total days in hospital [OR 1.04 (1.01–1.07)], immunosuppression [OR 2.04 (1.2–3.5)], a history of hyperlipidemia [OR 2.2 (1.2–3.8)], surgical history [OR 1.82 (1.05–3.14)] and age [OR 1.02 (1.00–1.04)] were identified as clinical factors independently associated to MDROs, while the Caucasian race was negatively associated to MDROs. The distribution of days on ventilation, days in hospital and days of antibiotic treatment prior to infection differed between the MDRO-positive and MDRO-negative groups. The MDRO-positive patients showed a greater median number of days in hospital and days of antibiotic treatment before infection, with a greater median number of days in hospital, days of antibiotic treatment and days of ventilation after infection, compared to the MDRO-negative patients. The mortality rate was not significantly different between the two groups. Appropriate empirical antibiotic therapy was prescribed in 82% of the MDRO-positive cases – such treatment being started within 24 h after onset of the infection in 68.5% of the cases. Conclusion Defining clinical factors associated with MDRO infections and administering timely and appropriate empirical antibiotic therapy may help reduce the mortality associated with these infections. In our hospital we did not withhold broad spectrum drugs as empirical therapy in patients with clinical features associated to MDRO infection. Our rate of appropriate empirical therapy was therefore high, which could explain the absence of excessive mortality in patients infected with MDROs.

To estimate the prevalence of ventilator-associated pneumonia caused by Pseudomonas aeruginosa in patients at risk for ventilator-associated pneumonia and to describe risk factors for P. aeruginosa ventilator-associated pneumonia.Prospective, observational study.ICUs at 56 sites in 11 countries across four regions: the United States (n = 502 patients), Europe (n = 495), Latin America (n = 500), and Asia Pacific (n = 376).Adults intubated and mechanically ventilated for 48 hours to 7 days, inclusive.None (local standard of care).Ventilator-associated pneumonia prevalence as defined by local investigators were 15.6% (293/1,873) globally, 13.5% in the United States, 19.4% in Europe, 13.8% in Latin America, and 16.0% in Asia Pacific (p = 0.04). Corresponding P. aeruginosa ventilator-associated pneumonia prevalences were 4.1%, 3.4%, 4.8%, 4.6%, and 3.2% (p = 0.49). Of 50 patients with P. aeruginosa ventilator-associated pneumonia who underwent surveillance testing, 19 (38%) had prior P. aeruginosa colonization and 31 (62%) did not (odds ratio, 7.99; 95% CI, 4.31-14.71). Of predefined risk factors for multidrug resistance (hereafter, risk factors), the most frequent in all patients were antimicrobial therapy within 90 days (51.9% of enrolled patients) and current hospitalization of more than or equal to 5 days (45.3%). None of these risk factors were significantly associated with P. aeruginosa ventilator-associated pneumonia by multivariate logistic regression. Risk factors associated with prior P. aeruginosa colonization were antimicrobial therapy within 90 days (odds ratio, 0.46; 95% CI, 0.29-0.73) and high proportion of antibiotic resistance in the community or hospital unit (odds ratio, 1.79; 95% CI, 1.14-2.82).Our findings suggest that ventilator-associated pneumonia remains a common ICU infection and that P. aeruginosa is one of the most common causative pathogens. The odds of developing P. aeruginosa ventilator-associated pneumonia were eight times higher in patients with prior P. aeruginosa colonization than in uncolonized patients, which in turn was associated with local resistance.

Background and objective The previous use of inhaled corticosteroids (ICS) may reduce the inflammatory response and mortality in patients with community-acquired pneumonia (CAP). Methods We measured serum levels of several inflammatory biomarkers, as well as mortality at various time-points, in 663 consecutive patients hospitalized for CAP; 128 (19%) were receiving chronic outpatient treatment with ICS. Patients on previous oral corticosteroids were excluded from the analysis. Results On admission, patients treated with ICS were older; had been diagnosed with chronic obstructive pulmonary disease (COPD), asthma and pneumonia in the previous year more often; and had higher CAP severity risk classes and lower tumour necrosis factor (TNF)-alpha (P

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae. We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy.

Background: Lymphopenic patients with community-acquired pneumonia (CAP) have shown high mortality rates. Corticosteroids have immunomodulatory properties and regulate cytokine storm in CAP. However, it is not known whether their modulatory effect on cytokine secretion differs in lymphopenic and non-lymphopenic patients with CAP. Therefore, we aimed to test whether the presence of lymphopenia may modify the response to corticosteroids (mainly in C reactive protein (CRP)) in patients with severe CAP and high inflammatory status). Methods: A post hoc analysis of a randomized controlled trial (NCT00908713) which evaluated the effect of corticosteroids in patients with severe CAP and high inflammatory response (CRP > 15 mg/dL). Patients were clustered according to the presence of lymphopenia (lymphocyte count below 1000 cell/mm3 ). Results: At day 1, 35 patients (59%) in the placebo group presented with lymphopenia, compared to 44 patients (73%) in the corticosteroid group. The adjusted mean changes from day 1 showed an increase of 1.19 natural logarithm (ln) cell/mm3 in the corticosteroid group and an increase of 0.67 ln cell/mm3 in the placebo group (LS mean difference of the changes in ln (methylprednisolone minus placebo) 0.51, 95% CI (0.02 to 1.01), p = 0.043). A significant effect was also found for the interaction (p = 0.043) between corticosteroids and lymphopenia in CRP values at day 3, with lower values in patients without lymphopenia receiving corticosteroids after adjustments for potential confounders. Conclusion: In this exploratory post hoc analysis from ramdomized controlled trial (RCT) data, the response to corticosteroids, measured by CRP, may differ according to lymphocyte count. Further larger studies are needed to confirm this data.

Background. Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. Methods. We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). Results. MDR pathogens were more common (15.3% vs 0.8%, P< .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P< .001); methicillin-resistant S. aureus (6.9% vs 0%, P= .003); Enterobacteriaceae (7.8% vs 2.4%, P= .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P= .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0–1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P< .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broadspectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P= .017), but among HCAP patients with 0–1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P= .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). Conclusions. Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. Clinical Trials Registration. Japan Medical Association Center for Clinical Trials, JMA-IIA00054.