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Background Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown. Research Question Do CAP survivors have evidence of increased inflammatory activity in their lung parenchyma on 2-deoxy-2-[18F]fluoro- d -glucose (18FDG)-PET/CT imaging after clinical resolution of infection? Study Design and Methods We obtained 18FDG-PET/CT scans from 22 CAP survivors during their hospitalization with pneumonia (acute CAP) and 30 to 45 days after hospital discharge (post-CAP). In each set of scans, we assessed the lungs for foci of increased 18FDG uptake by visual interpretation and by total pulmonary glycolytic activity (tPGA), a background-corrected measure of total metabolic activity (as measured by 18FDG uptake). We also measured, post-CAP, the glycolytic activity of CAP survivor lung areas with volumes similar to the areas in 28 matched historical control subjects without pneumonia. Results Overall, 68% of CAP survivors (95% CI, 45%-85%) had distinct residual areas of increased 18FDG uptake in their post-CAP studies. tPGA decreased from 821.5 (SD, 1,140.2) in the acute CAP period to 80.0 (SD, 81.4) in the post-CAP period (P = .006). The tPGA post-CAP was significantly higher than that in lung areas of similar volume in control subjects (80.0 [SD, 81.4] vs –19.4 [SD, 5.9]; P Interpretation An important proportion of CAP survivors have persistent pulmonary foci of increased inflammatory activity beyond resolution of their infection. As inflammation contributes to cardiovascular disease, cognitive decline, functional waning, and mortality risk in the general population, this finding provides a plausible mechanism for the increased morbidity and mortality that have been observed post-CAP.

Anti-fungal therapies remain sub-optimal, and resistant pathogens are increasing. New therapies are desperately needed, especially options that are less toxic than most of the currently available selection. In this review, I will discuss anti-fungal therapies that are in at least phase I human trials. These include VT-1161 and VT-1598, modified azoles with a tetrazole metal-binding group; the echinocandin rezafugin; the novel β-1,3-d-glucan synthase inhibitor ibrexafungerp; fosmanogepix, a novel anti-fungal targeting Gwt1; the arylamidine T-2307; the dihydroorotate inhibitor olorofim; and the cyclic hexapeptide ASP2397. The available data including spectrum of activity, toxicity and stage of clinical development will be discussed for each of these so clinicians are aware of promising anti-fungal agents with a strong likelihood of clinical availability in the next 5-7 years.

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.

Purpose of review Coronavirus disease 2019 (COVID-19) has produced an extraordinary amount of literature in a short time period. This review focuses on what the new literature has provided in terms of more general information about the management of community-acquired pneumonia (CAP). Recent findings Measures taken to reduce the spread of COVID-19 have caused a significant drop in influenza worldwide. Improvements in imaging, especially ultrasound, and especially in the application of rapid molecular diagnosis are likely to have significant impact on the management of CAP. Therapeutic advances are so far limited. Summary COVID-19 has taught us that we can do far more to prevent seasonal influenza and its associated mortality, morbidity and economic cost. Improvements in imaging and pathogen diagnosis are welcome, as is the potential for secondary benefits of anti-COVID-19 therapies that may have reach effect on respiratory viruses other than severe acute respiratory syndrome coronavirus 2. As community-transmission is likely to persist for many years, recognition and treatment of severe acute respiratory syndrome coronavirus 2 will need to be incorporated into CAP guidelines moving forward.

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.

Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Cases were defined as patients hospitalised at any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 1 April to 31 October 2019 (the 2019 influenza season), there were 4,154 patients admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 44% were elderly (≥ 65 years), 21% were children (< 16 years), 7.7% were Aboriginal and Torres Strait Islander peoples, 1.7% were pregnant and 73% had chronic comorbidities. Most admissions were due to influenza A infection (85%). Estimated vaccine coverage was 75% in the elderly, 49% in non-elderly adults with medical comorbidities, and 27% in young children (< 5 years). The estimated vaccine effectiveness in the target adult population was 42% (95% confidence interval [95% CI]: 36%, 49%). There were a larger number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2019 than in 2018.

Purpose of review Pulmonary nontuberculous mycobacterial disease (NTM) remains a significant clinical challenge with suboptimal therapy. This review focuses on recent understandings around the pathogenesis of NTM disease and nonantibiotic therapeutic approaches that are being pursued. Recent findings The absence of animal models that truly replicate human disease remains a major problem for NTM research with most findings coming from tuberculosis or tuberculosis-like studies. Recent research reiterates the known key roles of interferon gamma (IFNγ), tumor necrosis factor, interleukin-12 and granulocyte-macrophage colony stimulation factor (GM-CSF) in immunity to NTM. Autoantibodies to some of these factors may be important. Recent nonantibiotic research has focused on either boosting the immune response to NTM (e.g. with IFNγ or GM-CSF) or using other compounds to kill these pathogens (e.g. inhaled NO, gallium, etc.). Summary Our poor understanding of the immune deficit leading to NTM disease continues to hinder the development of highly effective therapies. New approaches are promising but need significant validation before being considered viable therapeutic options.

Introduction Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. Methods The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. Results There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. Discussion There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.

This review focuses on current knowledge of the epidemiology, prevention, and treatment of invasive pneumococcal (IPD) and meningococcal disease (IMD). IPD decreased significantly with the introduction of effective conjugate vaccines but is on the rise again. Effective antibiotic therapy of IPD includes the combination of a beta-lactam and a macrolide with additional considerations in meningitis. Steroids are mandatory in pneumococcal meningitis but not indicated in pneumococcal pneumonia except in the setting of refractory shock. There is increasing concern about the cardiovascular complications of IPD. IMD continues to be a significant health problem with major concerns about rising antibiotic resistance.

Background There are limited data regarding the relationship between interstitial lung disease (ILD) and the natural course of coronavirus disease 2019 (COVID-19). In this study, we investigate whether patients with ILD are more susceptible to COVID-19 than those without ILD and evaluate the impact of ILD on disease severity in patients with COVID-19. Methods A nationwide cohort of patients with COVID-19 (n=8070) and a 1:15 age-, sex-, and residence-matched cohort (n=121 050) were constructed between January 1, 2020 and May 30, 2020 in Korea. We performed a nested case-control study to compare the proportions of patients with ILD between the COVID-19 cohort and the matched cohort. Using the COVID-19 cohort, we also evaluated the risk of severe COVID-19 in patients with ILD versus those without ILD. Results The proportion of patients with ILD was significantly higher in the COVID-19 cohort than in the matched cohort (0.8% versus 0.4%, p

Background Inadequate isolation of patients with active pulmonary tuberculosis causes exposure whereas over-cautious isolation generates time and cost inefficiencies. This study aims to ascertain the delays involved in isolating subjects and the importance of risk factors. Methods and material Between December 2010 and January 2013, a retrospective analysis of 271 subjects was performed. Information was obtained from discharge letters, radiological and microbiological results. Results The median time taken to isolate subjects was 0 days, and 71.7% were isolated within 1 day. Most subjects (75.3%) had sputum samples obtained after isolation, of which 14.7% were positive. The median time from admission to first sputum sample was 1 day. Smear was negative in 174 subjects (85.3%). Country of birth (high or low risk) did not significantly affect sputum positivity (25.5% vs 19.4%, p = 0.52). Suspicious radiological findings were noted in 38.6% subjects, and 32.8% had a suspicious clinical history. Subjects with both clinical and radiological probability had more sputum positivity (46.2%), compared to subjects who had neither (2.7%). Conclusion There are delays with isolation and diagnosis of subjects with a high probability of tuberculosis. Clinical and radiological probability were more significant in predicting sputum positivity than country of birth.

BACKGROUND: In adults hospitalized with community-acquired pneumonia (CAP), increasing ward-based walking may reduce length of stay (LOS). There are few data to describe ward-based walking in this population. In adults hospitalized with CAP, we aimed to report variables of walking and non-walking time, to determine whether demographic or clinical variables influenced daily step count, and to determine whether daily step count influenced LOS. METHODS: Following admission, daily step count and variables related to walking and non-walking time were quantified using the StepWatch Activity Monitor. Details regarding demographics, clinical characteristics, clinical care, and LOS were extracted from the medical records and hospital electronic data systems. Frailty was calculated via the 7-point Clinical Frailty Scale; disease severity was measured via the CURB-65 score. Health care utilization at 30 d following discharge was measured via telephone interview. RESULTS: Two hundred participants completed the study, of whom 121 contributed ≥ 24 h of data from the StepWatch Activity Monitor. The median (interquartile range (IQR)) number of daily steps was 926 (457–1706). These were accumulated over 66 (41–121) min/d, with a usual bout duration of 3 (2–4) min and 1-min peak cadence of 56 (43–74) steps/min. An average of 93% (89–96) of waking hours was spent in non-walking time. In the multivariable model, increased frailty was retained as a predictor of lower step count (incidence rate ratio [IRR] 0.59, 95% CI 0.41–0.85). For every increase in 500 steps/d, LOS reduced by 11% (IRR 0.89, 95% CI 0.80–0.99). CONCLUSIONS: Subjects hospitalized with CAP did very little walking, most of which was accumulated in short bouts at a low intensity. Compared with subjects with mild frailty, those with moderate to severe frailty took 59% fewer steps per day. Those with a higher daily step count had a shorter LOS.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

Objective: In adults hospitalized with an acute or chronic respiratory condition, to determine what has been reported regarding exercise programmes in terms of content, tolerability, evaluation and adverse events. Data sources: A systematic search was conducted of electronic databases (PubMed, EMBASE, CINAHL, PEDro, The Cochrane Library), trial registries and conference abstracts (Thoracic Society of Australia and New Zealand Annual Scientific Meeting, the European Respiratory Society Congress, the American Thoracic Society International Conference). Review methods: Studies were included if they (1) recruited adults hospitalized with an acute or chronic respiratory condition, (2) described an exercise programme that targeted peripheral muscles and (3) reported that ⩾80% of the sample had initiated training within 72 hours of hospitalization. Results: The last search was conducted on 2 June 2019. Of the 6282 records identified, 20 met the study criteria. These described 18 separate studies (2018 participants). Studies were conducted in adults hospitalized with an exacerbation of chronic obstructive pulmonary disease or with community-acquired pneumonia. The content of exercise programmes included aerobic and/or resistance training, neuromuscular electrical stimulation, whole-body vibration or movement out of bed. In eight studies (44%), the initial session was prescribed using objective measures of exercise capacity, peripheral muscle force and the ability to undertake activities of daily living. Across 7420 training sessions, seven adverse events were reported. Conclusion: Methods used to prescribe and titrate exercise programmes in adults hospitalized with an acute or an exacerbation of a chronic respiratory condition were disparate. When reported, programmes were well tolerated and adverse events were infrequent.

Ninety‐five adults enrolled in the Etiology of Pneumonia in the Community study with negative admission influenza polymerase chain reaction (PCR) tests received influenza vaccination during hospitalization. Acute and convalescent influenza serology was performed. After vaccination, seropositive (≥1:40) hemagglutination antibody titers (HAI) were achieved in 55% to influenza A(H1N1)pdm09, 58% to influenza A(H3N2), 77% to influenza B (Victoria), and 74% to influenza B (Yamagata) viruses. Sixty‐six (69%) patients seroconverted (≥4‐fold HAI rise) to ≥1 strain. Failure to seroconvert was associated with diabetes, bacterial detection, baseline seropositive titers for influenza B (Yamagata), and influenza vaccination in the previous season.

"Health care-associated pneumonia (HCAP) was introduced into guidelines because of concerns about the increasing prevalence of drug-resistant pathogens (DRPs) not covered by standard empirical therapy. We now know that DRPs are very localized phenomena with low rates in most sites. Although HCAP risk factors are associated with a higher mortality, this is driven by comorbidities rather than the pathogens. Empirical coverage of DRPs has generally not resulted in better patient outcomes. A far more nuanced approach must be taken for patients with risk factors for DRPs taking into account the local cause and severity of disease.

COVID-19; Clinical research COVID-19; Recerca clínica COVID-19; Investigación clínica Clinical research studies reporting on post COVID-19 condition should follow some basic recommendations.

The diagnosis of pneumonia is both simple and complex. Recent research is challenging our concept of pneumonia and radiological gold standards that have underpinned research for decades. In particular, the accuracy of chest radiographs in diagnosing pneumonia is now highly questionable when compared with computed tomography scans. Depending on the question being asked, pneumonia can be defined in clinical, pathological, radiological, or microbiological contexts, or frequently a combination of all of these. However, while the field is changing, until we have new studies defining pneumonia in new ways, clinicians can be reassured that existing guidelines based on “old” standards remain as valid as they have always been., Recent research has challenged our concept of pneumonia. New studies will define pneumonia in new ways, but clinicians can be reassured that existing guidelines based on “old” standards remain valid. https://bit.ly/3kJiV2N

Community-acquired pneumonia is one of the commonest and deadliest of the infectious diseases, yet our understanding of it remains relatively poor. The recently published American Thoracic Society and Infectious Diseases Society of America Community-acquired pneumonia guidelines acknowledged that most of what we accept as standard of care is supported only by low quality evidence, highlighting persistent uncertainty and deficiencies in our knowledge. However, progress in diagnostics, translational research, and epidemiology has changed our concept of pneumonia, contributing to a gradual improvement in prevention, diagnosis, treatment, and outcomes for our patients. The emergence of considerable evidence about adverse long-term health outcomes in pneumonia survivors has also challenged our concept of pneumonia as an acute disease and what treatment end points are important. This review focuses on advances in the research and care of community-acquired pneumonia in the past two decades. We summarize the evidence around our understanding of pathogenesis and diagnosis, discuss key contentious management issues including the role of procalcitonin and the use or non-use of corticosteroids, and explore the relationships between pneumonia and long-term outcomes including cardiovascular and cognitive health.

Highlights • Severe COVID-19 presents as multiple organ dysfunction syndrome (SARS-CoV-2 MODS) • Less is more in ventilating critically ill patients with severe COVID-19 pneumonia • European Medicines Agency released approval for administration of steroids • Main therapeutic targets: anti-inflammatory; anticoagulation; protective ventilation, The 2020 International Web Scientific Event in COVID-19 pandemic in critically ill patients aimed at updating the information and knowledge on the COVID-19 pandemic in the intensive care unit. Experts reviewed the latest literature relating to the COVID-19 pandemic in critically ill patients, such as epidemiology, pathophysiology, phenotypes of infection, COVID-19 as a systematic infection, molecular diagnosis, mechanical ventilation, thromboprophylaxis, COVID-19 associated co-infections, immunotherapy, plasma treatment, Catheter-Related bloodstream infections, artificial intelligence for COVID-19, and vaccination. Antiviral therapy and co-infections are out of the scope of this review. In this review, each of these issues is discussed with key messages regarding management and further research being presented after a brief review of available evidence.

Bronchiectasis is reported to be more frequent in females. There have been no large studies examining the impact of biological sex on disease characteristics, aetiology, severity, quality of life or management. Patients were prospectively enrolled from 2015 -2018 in 3 linked bronchiectasis registries in Australia, Europe and India. Disease information was collected, including quality of life (QoL-B). Analyses were conducted cross-sectionally using baseline data. 13859 patients were included from 29 countries. 57.6% were female. The highest proportion of females were in Australia (70.9%) and lowest in India (43.1%). Male sex was associated with bronchiectasis caused by COPD and TB; while female sex was associated with post-infectious bronchiectasis, asthma, connective tissue disease and NTM. Men had more severe disease as measured by the bronchiectasis severity index, but females more likely to be infected with Pseudomonas aeruginosa. Women had greater disease impact across multiple QoL-B domains including social, emotional and treatment burden domains. Cough and sputum purulence were more severe in women while men most frequently complained of wheeze and breathlessness. Men were significantly less likely to receive evidence based interventions including testing for immunodeficiency and ABPA, long term antibiotic treatment for frequent exacerbators, pulmonary rehabilitation and airway clearance techniques. Conclusion: There are striking sex differences in aetiology, severity, quality of life and treatment in patients with bronchiectasis

Introduction: Pulmonary rehabilitation is recommended for people with bronchiectasis, but the content for an educational program is not directed towards people with this condition. The goal of the qualitative study was to identify the educational needs of people with bronchiectasis in a pulmonary rehabilitation setting. Methods: A qualitative study of people with bronchiectasis, registered on the Australian Bronchiectasis Registry using individual semi-structured interviews was undertaken. Transcripts were coded independently by two investigators and themes developed through consensus. Results: A total of 21 people with bronchiectasis (mean age 72±11 years, FEV1 83.1±25.4% predicted) participated in an interview. Participants indicated they have a good understanding of their condition, which factors may increase risk of an acute exacerbation, their medications and that physiotherapy is an important part of treatment. Major themes for which further education was sought were the scope of airway clearance therapy options, methods of maintaining motivation for physiotherapy, coping strategies for psychosocial symptoms, and how to self-manage their condition. Participants perceived benefit in receiving information in a group setting. Conclusions: Unmet education needs of people with bronchiectasis include options for airway clearance therapy, development of coping strategies to manage the psychosocial challenges of the condition and self-management. This may provide a foundation for the development of structured education sessions that could be delivered within pulmonary rehabilitation for this population.

Background and objective Hospital readmissions within 30 days are used as an indicator of quality of hospital care. We aimed to evaluate the ability of the LACE (Length of stay, Acuity of admission, Comorbidities based on Charlson comorbidity score and number of Emergency visits in the last 6 months) index to predict the risk of 30-day readmissions in patients hospitalised for community-acquired pneumonia (CAP). Methods In this retrospective cohort study a LACE index score was calculated for patients with a principal diagnosis of CAP admitted to a tertiary hospital in Sydney, Australia. The predictive ability of the LACE score for 30-day readmissions was assessed using receiver operator characteristic curves with C-statistic. Results Of 3996 patients admitted to hospital for CAP at least once, 8.0% (n=327) died in hospital and 14.6% (n=584) were readmitted within 30 days. 17.8% (113 of 636) of all 30-day readmissions were again due to CAP, followed by readmissions for chronic obstructive pulmonary disease, heart failure and chest pain. The LACE index had moderate discriminative ability to predict 30-day readmission (C-statistic=0.6395) but performed poorly for the prediction of 30-day readmissions due to CAP (C-statistic=0.5760). Conclusions The ability of the LACE index to predict all-cause 30-day hospital readmissions is comparable to more complex pneumonia-specific indices with moderate discrimination. For the prediction of 30-day readmissions due to CAP, the performance of the LACE index and modified risk prediction models using readily available variables (sex, age, specific comorbidities, after-hours, weekend, winter or summer admission) is insufficient., The LACE index is easy to use and its ability to predict all-cause 30-day hospital readmissions for patients hospitalised with community-acquired pneumonia is comparable to more complex pneumonia-specific indices with moderate discrimination https://bit.ly/2SYkxam

BackgroundThe 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.PurposeThe goal of the study was to evaluate the efficacy of the CORE process had it been used to develop the ATS/IDSA CAP guidelines.MethodsExperts 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.ResultsUsing 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%).ConclusionsIf 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.

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.

No abstract available.

Purpose of review The American Thoracic Society and Infectious Diseases Society of America recently released their joint guideline for the diagnosis and treatment of adults with community-acquired pneumonia (CAP). The co-chairs of the guideline committee provide a summary of the guideline process, key recommendations from the new guideline and future directions for CAP research. Recent findings The guideline committee included 14 experts from the two societies. Sixteen questions for the guideline were selected using the PICO format. The GRADE approach was utilized to review the available evidence and generate recommendations. The recommendations included expanded microbiological testing for patients suspected of drug-resistant infections, empiric first-line therapy recommendations for outpatients and inpatients including use of beta-lactam monotherapy for uncomplicated outpatients, elimination of healthcare-associated pneumonia as a treatment category, and not recommending corticosteroids as routine adjunct therapy. Summary CAP is a major cause of morbidity and mortality. Effective antibiotic therapy is available and remains largely empirical. New diagnostic tests and treatment options are emerging and will lead to guideline updates in the future.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administration of vancomycin would overcome these limitations, we developed a dry powder formulation suitable for inhalation (AeroVanc). Here, we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability of AeroVanc. In part I, 18 healthy subjects received a single dose of 16 mg, 32 mg, or 80 mg of AeroVanc. Two subjects also received a 250-mg dose of intravenous vancomycin. In part 2 of the study, 32 mg and 80 mg AeroVanc were administered to subjects with cystic fibrosis as single doses. There were no serious side effects. A small drop in forced expiratory volume in 1 s (FEV(1)) was observed in 3 subjects with cystic fibrosis, one of whom required salbutamol. Vancomycin was rapidly absorbed after inhalation. Peak and mean plasma concentrations of vancomycin were dose proportional. The average minimum concentration of vancomycin in sputum remained above the usual MIC values for MRSA for up to 24 h (minimum sputum concentration [C(min)], 32-mg dose = 3.05 μg/ml, 80-mg dose = 8.0 μg/ml). In conclusion, AeroVanc was well tolerated and achieved high levels in sputum with a mean systemic absorption of 49%, making it a potential therapeutic strategy for respiratory infection with MRSA.

International audience; BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS: In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.). Copyright © 2020 Massachusetts Medical Society.

BACKGROUND This study investigated the association between nadir anemia and mortality and length of stay (LOS) in a general population of hospitalized patients. STUDY DESIGN AND METHODS A retrospective cohort study of tertiary hospital admissions in Western Australia between July 2010 and June 2015. Outcome measures were in-hospital mortality and LOS. RESULTS Of 80,765 inpatients, 45,675 (56.55%) had anemia during admission. Mild and moderate/severe anemia were independently associated with increased in-hospital mortality (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.36-1.86, p = 0.001; OR 2.77, 95% CI 2.32-3.30, p < 0.001, respectively). Anemia was also associated with increased LOS, demonstrating a larger effect in emergency (mild anemia-incident rate ratio [IRR] 1.52, 95% CI 1.48-1.56, p < 0.001; moderate/severe anemia-IRR 2.18, 95% CI 2.11-2.26, p < 0.001) compared to elective admissions (mild anemia-IRR 1.30, 95% CI 1.21-1.41, p < 0.001; moderate/severe anemia-IRR 1.69, 95% CI 1.55-1.83, p < 0.001). LOS was longer in patients who developed anemia during admission compared to those who had anemia on admission (IRR 1.13, 95% CI 1.10-1.17, p < 0.001). Red cell transfusion was independently associated with 2.23 times higher odds of in-hospital mortality (95% CI 1.89-2.64, p < 0.001) and 1.31 times longer LOS (95% CI 1.25-1.37, p < 0.001). CONCLUSION More than one-third of patients not anemic on admission developed anemia during admission. Even mild anemia is independently associated with increased mortality and LOS; however, transfusion to treat anemia is an independent and additive risk factor.

Background and objective Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period. Methods Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted. Results In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). Conclusion This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

Background The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain. Methods In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data. Results The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%). Conclusions Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.

Despite modern healthcare practices and antimicrobial agents, community-acquired pneumonia (CAP) and associated parapneumonic effusion (PPE) are still common, associated with significant morbidity and mortality, and responsible for significant healthcare system costs globally. There is a need for adjunctive therapies to improve their clinical outcomes. The use of corticosteroids as an adjunctive therapy to suppress the inflammatory response in CAP has received significant attention. In this paper, we review in detail the randomized clinical trials to date on the use of corticosteroids in CAP. Despite the large number of studies and optimism, the current evidence is inconclusive to warrant recommendation of the routine use of corticosteroids in CAP. The use of corticosteroid in PPE is also attracting interests which largely arose from indirect evidence. Direct placebo-controlled trials are required.