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We assessed whether multiplex real-time PCR plus conventional microbiological testing is safe and more effective than conventional microbiological testing alone for reducing antibiotic use in community-acquired pneumonia (CAP). In this randomised trial, we recruited adults hospitalised with CAP at four Spanish hospitals. Patients were randomly assigned (1:1) to undergo either multiplex real-time PCR in non-invasive respiratory samples plus conventional microbiological testing or conventional microbiological testing alone. The primary endpoint was antibiotic use measured by days of antibiotic therapy (DOT). Between February 20, 2020, and April 24, 2023, 242 patients were enrolled; 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. All but one of the patients allocated to multiplex real-time PCR plus conventional microbiological testing underwent PCR, which was performed in sputum samples in 77 patients (65.2%) and in nasopharyngeal swabs in 41 (34.7%). The median DOT was 10.04 (IQR 7.98, 12.94) in the multiplex PCR plus conventional microbiological testing group and 11.33 (IQR 8.15, 16.16) in the conventional microbiological testing alone group (difference -1.04; 95% CI, -2.42 to 0.17; p = 0.093). No differences were observed in adverse events and 30-day mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Clinicaltrials.gov registration: NCT04158492., (© 2024. The Author(s).)

Objectives: The usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP., Methods: A retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model., Results: Of 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96-3.41) and clinical stability at day 3 (AOR 1.87; 1.45-2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14-1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53-1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35-1.14))., Discussion: Antimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite adequate antibiotic coverage, community-acquired pneumonia (CAP) remains a leading cause of hospitalization and mortality worldwide. It induces both a local pulmonary and a systemic inflammatory response, particularly significant in severe cases. The intensity of the dysregulated host response varies from patient to patient and has a negative impact on survival and other outcomes., Areas Covered: This comprehensive review summarizes the pathophysiological aspects of the inflammatory response in CAP, briefly discusses the usefulness of biomarkers, and assesses the clinical evidence for modulating the inflammatory pathways. We searched PubMed for the most relevant studies, reviews, and meta-analysis until August 2020., Expert Opinion: Notable efforts have been made to identify biomarkers that can accurately differentiate between viral and bacterial etiology, and indeed, to enhance risk stratification in CAP. However, none has proven ideal and no recommended biomarker-guided algorithms exist. Biomarker signatures from proteomic and metabolomic studies could be more useful for such assessments. To date, most studies have produced contradictory results concerning the role of immunomodulatory agents (e.g. corticosteroids, macrolides, and statins) in CAP. Adequately identifying the population who may benefit most from effective modulation of the inflammatory response remains a challenge.

Malnutrition comprises two groups of conditions: undernutrition and overweight or obesity. It has been associated with a high risk of contracting infectious diseases and with elevated mortality rates. Community-acquired pneumonia (CAP) is one of the most common infectious diseases worldwide and its prognosis is affected by a large number of recognizable risk factors. This narrative review updates the information on the impact of malnutrition, including both undernutrition and obesity, on the risk and prognosis of adults with CAP. Studies of CAP that have evaluated undernutrition have applied a variety of definitions when assessing the nutritional status of patients. Undernutrition has been associated with unfavorable clinical outcomes, such as prolonged hospital stay, need for intensive care unit admission, and mortality; in contrast, most published studies have found that increased body mass index is significantly associated with higher survival in patients with CAP. However, some authors have presented divergent results, mainly in relation to the etiology of CAP (bacterial versus viral). Influenza infection, caused by influenza A (H1N1) pdm09, has been associated with worse prognosis in obese patients. The current data underscore the need for larger studies to examine the physiological mechanisms that explain the differential impact of malnutrition on outcomes. Achieving a better understanding may help to guide the design of new interventions to improve prognosis.

Introduction: Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP., Methods: We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression., Results: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression., Conclusions: The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Community-acquired pneumonia (CAP) remains a leading cause of death worldwide, and hypoalbuminemia is associated with worse outcomes. However, it remains uncertain whether albumin administration could have any beneficial effects. We aim to assess whether the administration of albumin in hypoalbuminemic patients with CAP increases the proportion of clinically stable patients at day 5 compared with the standard of care alone., Methods: This is a trial protocol for a superiority, non-blinded, multicenter, randomized, phase 3, interventional controlled clinical trial. The primary endpoint will be the proportion of clinical stable patients at day 5 (intention to treat), defined as those with stable vital signs for at least 24 h. The secondary endpoints will be time to clinical stability, duration of intravenous and total antibiotic treatment, length of hospital stay, intensive care unit admission, duration of mechanical ventilation and vasopressor treatment, adverse events, readmission within 30 days, and all-cause mortality. The trial has been approved by the Spanish Medicines and Healthcare Products Regulatory Agency. The investigators commit to publish the data in peer-reviewed journals within a year of the study completion date. Subjects will be recruited from three Spanish hospitals over a planned enrolment period of 2 years. A follow-up visit will be performed 1 month after discharge. We have estimated the need for a sample size of 360 patients at a two-sided 5% alpha-level with a power of 80% based on intention to treat. Eligible participants must be hospitalized, hypoalbuminemic (≤ 30 g/L), non-immunosuppressed, adults, and diagnosed with CAP. They will be randomly assigned (1:1) to receive standard care plus albumin (20 g in 100 mL) every 12 h for 4 days or standard care alone., Discussion: If this randomized trial confirms the hypothesis, it should lead to a change in current clinical practice for the management of hypoalbuminemic patients with CAP., Trial Registration: European Clinical Trials Database (EudraCT) 2018-003117-18 . Registered on 12 April 2019. ClinicalTrials.gov NCT04071041 . Registered on 27 August 2019.

Background: Implementation of sputum Gram stain in the initial assessment of community-acquired pneumonia (CAP) patients is still controversial. We performed a systematic review and meta-analysis to investigate the usefulness of sputum Gram stain for defining the etiologic diagnosis of CAP in adult patients., Methods: We systematically searched the Medline, Embase, Science Direct, Scopus and LILACS databases for full-text articles. Relevant studies were reviewed by at least three investigators who extracted the data, pooled them using a random effects model, and carried out quality assessment. For each bacterium (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Gram-negative bacilli), pooled sensitivity, specificity, positive and negative likelihood ratios were reported., Results: After a review of 3539 abstracts, 20 articles were included in the present meta-analysis. The studies included yielded 5619 patients with CAP. Pooled sensitivity and pooled specificity of sputum Gram stain were 0.59 (95% CI, 0.56-0.62) and 0.87 (95% CI, 0.86-0.89) respectively for S. pneumoniae, 0.78 (95% CI, 0.72-0.84) and 0.96 (95% CI, 0.94-0.97) for H. influenzae, 0.72 (95% CI, 0.53-0.87) and 0.97 (95% CI, 0.95-0.99) for S. aureus, and 0.64 (95% CI, 0.49-0.77) and 0.99 (95% CI, 0.97-0.99) for Gram-negative bacilli., Conclusion: Sputum Gram stain test is sensitive and highly specific for identifying the main causative pathogens in adult patients with CAP., Trial Registration: This study has been registered at PROSPERO International prospective register of systematic reviews under registration no. CRD42015015337 .

Introduction: Community-acquired pneumonia (CAP) continues to be a leading cause of hospitalization and mortality worldwide. Streptococcus pneumoniae and Legionella pneumophila remain the major etiological agents and are responsible for a significant proportion of CAP mortality. Among diagnostic tests for CAP, urine antigen detection of S. pneumoniae and L. pneumophila is widely accepted due to the simplicity of collection and the rapidity of the test results. Areas covered: This comprehensive review outlines the urinary antigen tests available, discusses their sensitivity and specificity, and assesses the usefulness of their results as the basis for targeted therapy. Expert commentary: There have been advances in urine antigen detection tests for patients with CAP. New methodologies show greater sensitivity, detect S. pneumoniae and L. pneumophila in a single test, and also detect pneumococcal serotypes. In addition, urine antigen detection tests have shown a high specificity, which means that a positive result practically indicates the causative pathogen of CAP. Therefore, a positive result can lead to a targeted therapy that is likely to improve patient outcomes and reduce the risk of resistance and adverse events. However, well-designed studies are needed to evaluate the usefulness of urine antigen detection tests with regard to clinical outcomes.

Introduction: Community-acquired pneumonia (CAP) is an increasing problem in the elderly that is associated with elevated morbidity and mortality. Given the expected increased life expectancy, this problem is only likely to worsen, so it has been considered that treatment effects must be examined separately in elderly adults with CAP. Areas covered: In this narrative review, we give an update of the available data of antibiotics for elderly patients with CAP. Clinical features, drug pharmacokinetics and pharmacodynamics, adverse effects, and outcomes differ in CAP depending on patient age. Older age, for example, can affect the effect of specific antibiotic regimens on important CAP clinical outcomes. Current guidelines do not offer specific recommendations for the management of CAP in elderly patients. Expert opinion: Most of our knowledge about the treatment of CAP in elderly patients has been gained from studies in young populations. However, elderly patients with CAP deserve special attention because there are several factors in this population that could influence their response to antibiotic regimens in CAP.

Introduction: Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

Background: Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking., Methods: We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses., Results: Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (OR = 0.83, 95% CI = 0.24-2.81), but it was found to be a protective factor for prolonged LOS (above the median) (OR = 0.46, 95% CI = 0.30-0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV-V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (<30 days)., Conclusions: Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as β-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.

Objectives: The pneumonia severity index and CURB-65 are risk assessment tools widely used in community-acquired pneumonia (CAP). However, limitations in these prognostic scores have led to increasing interest in finding biomarkers that might provide additional information. To date, the role of these biomarkers has not been fully elucidated., Methods: We systematically searched the Medline, Web of Knowledge, Science Direct, and LILACS databases. We included studies that assessed the accuracy of biomarkers for the prediction of in-hospital or ≤30-day mortality, in hospitalized adults with CAP. Two independent investigators extracted patient and study characteristics, which were thereafter pooled using a random effects model. Relationships between sensitivity and specificity of biomarkers and prognostic scores were plotter using the area under the receiver operator characteristic curve (AUC)., Results: We included 24 articles and 2 databases from 1069 reviewed abstracts, which provided 10,319 patients for analysis. Reported mortality rates varied from 2.4% to 34.6%. The highest AUC values for predicting mortality were associated with pro-adrenomedullin (0.80) and prohormone forms of atrial natriuretic peptide (0.79), followed by cortisol (0.78), procalcitonin (0.75), copeptin (0.71), and C-reactive protein (0.62). There were no statistically significant differences between the AUCs of the studied biomarkers, other than for copeptin and C-reactive protein, which performed comparatively poorly. When compared with the CAP-specific scores, the AUCs were not significantly different from those of most biomarkers., Conclusions: The identified biomarkers are able to predict mortality with moderate to good accuracy in CAP. However, biomarkers have no clear advantage over CAP-specific scores for predicting mortality., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge., Methods: A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed., Results: We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003)., Conclusions: The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP., Trial Registration: Controlled-Trials.com ISRCTN39531840.

Background: Community-acquired pneumonia (CAP) is a frequent complication of chronic obstructive pulmonary disease (COPD), but previous studies are often contradictory., Objectives: We aimed to ascertain the characteristics and outcomes of CAP in patients with COPD as well as to determine the risk factors for mortality and Pseudomonas aeruginosa pneumonia in COPD patients with CAP. We also describe the etiology and outcomes of CAP in COPD patients receiving chronic oxygen therapy at home and those receiving inhaled steroids., Methods: An observational analysis of a prospective cohort of hospitalized adults with CAP (1995-2011) was performed., Results: We documented 4121 CAP episodes, of which 983 (23.9%) occurred in patients with COPD; the median FEV1 value was 50%, and 57.8% were classified as stage III or IV in the GOLD classification. Fifty-eight per cent of patients were receiving inhaled steroids, and 14.6% chronic oxygen therapy at home. Patients with COPD presented specific clinical features. S. pneumoniae was the leading causative organism overall, but P. aeruginosa was more frequent in COPD (3.4 vs. 0.5%; p<0.001). Independent risk factors for case-fatality rate in patients with COPD were multilobar pneumonia, P. aeruginosa pneumonia, and high-risk PSI classes. Prior pneumococcal vaccination was found to be protective. FEV1 was an independent risk factor for P. aeruginosa pneumonia., Conclusions: CAP in patients with COPD presents specific characteristics and risk factors for mortality. Prior pneumococcal vaccine has a beneficial effect on outcomes. P. aeruginosa pneumonia is associated with low FEV1 values and poor prognosis.

Objective: To identify the incidence, causes, timing and risk factors associated with 1-year mortality in CAP patients after hospital discharge., Methods: Adult patients with CAP who were admitted to a tertiary hospital from 2007 to 2011 were prospectively recruited and followed up for 1 year after hospital discharge., Results: Of the 1284 patients discharged, 93 (7.2%) died within 1-year of leaving hospital. Sixty eight (73.1%) patients died in the first six months. The main reasons for 1-year mortality after hospital discharge were infectious diseases, mainly pneumonia, followed by acute cardiovascular events. Mortality from infectious diseases was higher during the first 6 months (86.1%), while the number of deaths from cardiovascular causes was stable throughout the months of follow-up. After adjustment for confounders, chronic obstructive pulmonary disease, diabetes mellitus, cancer, dementia, rehospitalization within 30 days of hospital discharge and nursing home were independently associated with 1-year mortality. The incidence of long-term mortality increased >50% when ≥4 risk factors were present (P < .001)., Conclusions: Patients mainly died from infectious diseases and acute cardiovascular events in the first six months after leaving hospital for an acute CAP episode. Certain features may help to identify the risk of long-term mortality in CAP patients., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen which causes a variety of respiratory infections. The objectives of the study were to determine its antimicrobial susceptibility, to characterize the β-lactam resistance, and to establish a genetic characterization of NTHi isolates. Ninety-five NTHi isolates were analyzed by pulsed field gel electrophoresis (PFGE) and multi locus sequence typing (MLST). Antimicrobial susceptibility was determined by microdilution, and the ftsI gene (encoding penicillin-binding protein 3, PBP3) was PCR amplified and sequenced. Thirty (31.6%) isolates were non-susceptible to ampicillin (MIC ≥ 2 mg/L), with 10 of them producing β-lactamase type TEM-1 as a resistance mechanism. After ftsI sequencing, 39 (41.1%) isolates showed amino acid substitutions in PBP3, with Asn526 → Lys being the most common (69.2%). Eighty-four patients were successfully treated with amoxicillin/clavulanic acid, ceftriaxone and levofloxacin. Eight patients died due either to aspiration or complication of their comorbidities. In conclusion, NTHi causing CAP in adults shows high genetic diversity and is associated with a high rate of reduced susceptibility to ampicillin due to alterations in PBP3. The analysis of treatment and outcomes demonstrated that NTHi strains with mutations in the ftsI gene could be successfully treated with ceftriaxone or fluoroquinolones.

Objectives: To determine the aetiology, clinical features and prognosis of CAP during the first post-pandemic influenza season. We also assessed the factors associated with severe disease and tested the ability of a scoring system for identifying influenza A (H1N1)pdm09-related pneumonia., Methods: Prospective cohort study carried out at 10 tertiary hospitals of Spain. All adults hospitalised with CAP from December 01, 2010 to March 31, 2011 were analysed., Results: A total of 747 adults with CAP required hospitalisation. The aetiology was determined in 315 (42.2%) patients, in whom 154 (21.9%) were due to bacteria, 125 (16.7%) were due to viruses and 36 (4.8%) were mixed (due to viruses and bacteria). The most frequently isolated bacteria were Streptococccus pneumoniae. Among patients with viral pneumonia, the most common organism identified were influenza A (H1N1)pdm09. Independent factors associated with severe disease were impaired consciousness, septic shock, tachypnea, hyponatremia, hypoxemia, influenza B, and influenza A (H1N1)pdm09. The scoring system evaluated did not differentiate reliably between patients with influenza A (H1N1)pdm09-related pneumonia and those with other aetiologies., Conclusions: The frequency of bacterial and viral pneumonia during the first post-pandemic influenza season was similar. The main identified virus was influenza A (H1N1)pdm09, which was associated with severe disease. Although certain presenting clinical features may allow recognition of influenza A (H1N1)pdm09-related pneumonia, it is difficult to express them in a reliable scoring system., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Early identification of patients with community-acquired pneumonia (CAP) at risk of poor outcome is critical for defining site of care and may impact on hospital resource consumption and prognosis. The Pneumonia Severity Index and CURB-65 are clinical rules that accurately identify individuals at risk of death. However, these scores have some limitations. Therefore in recent years, increasing attention has been being paid to research on biomarkers, since they have the potential to resolve fundamental issues regarding prognostic prediction that cannot be readily addressed using CAP-specific scores. Nevertheless, the use of biomarkers in this context needs to be validated in prospective trials so as to elucidate how they can best be applied in practice. This review examines the usefulness of biomarkers, whether used alone or in conjunction with other clinical severity of illness scores, for identifying CAP patients at risk of short- and long-term mortality and for predicting both the need for intensive care unit admission and the potential for treatment failure.

Objective: To investigate whether serum albumin levels within 24 h of admission correlate with outcomes in community-acquired pneumonia (CAP)., Methods: Observational analysis of a prospective cohort of adults with CAP requiring hospitalization from 1995 through 2011. Serum albumin level was the independent variable. The primary end point was 30-day mortality., Results: During the study period, 3463 patients with CAP required hospitalization. The median value of albumin was 31 g/L (IQR 28-35). As levels of serum albumin decrease, the risk of complications significantly increases (P < .001). Decreased albumin levels were also associated with prolonged time to reach clinical stability (P < .001), prolonged hospital stay (P < .001), ICU admission (P < .001), the need for mechanical ventilation (P < .001), and 30-day mortality (P < .001). After adjusting for potential confounders in a multivariate logistic regression analysis, serum albumin levels at admission (-5 g/L decrease) were independently associated with a higher risk of 30-day mortality (OR 2.11, 95% CI 1.73-2.56). For predicting primary end point, hypoalbuminemia (<30 g/L) significantly increased the area under ROC curves of PSI and CURB-65 scores (P ≤ .02), and identified those patients with higher risk of complications classified into low- and high-risk groups by these scores., Conclusions: Serum albumin level within 24 h of admission is a good prognostic marker in CAP. Physicians should consider albumin level when evaluating the severity of illness in patients with CAP., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the risk factors and the prognosis of acute cardiac events in patients with community-acquired pneumonia (CAP)., Methods: Observational analysis of a prospective cohort of hospitalized adults with CAP (1995-2010). A logistic regression analysis was performed to identify predictors for acute cardiac events and mortality., Results: Of 3921 patients with CAP, 315 (8%) had one or more acute cardiac events during hospitalization (199 new-onset or worsening cardiac arrhythmias, 118 new-onset or worsening congestive heart failure and/or 30 myocardial infarction). In the multivariate analysis, factors associated with these events were age >65 years, chronic heart disease, chronic kidney disease, tachycardia, septic shock, multilobar pneumonia, hypoalbuminemia, and pneumococcal pneumonia. A rule based on these variables had an area under ROC curve of 0.73 (95% CI 0.70-0.76) to predict acute cardiac events. These complications occurred in 2.8% of patients classified in the low-risk (≤3 points), 9.7% in the intermediate-risk (4-5 points) and 21.2% in the high-risk (≥6 points) groups (P < .001). The overall case fatality rate was higher in patients who had acute cardiac events (19.4% vs. 6.4%; P < .001)., Conclusion: Acute cardiac events occur frequently during hospitalization for CAP and are associated with poor prognosis. A simple rule based on demographic and clinical features may help identify patients at higher risk of these complications., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

We performed an observational analysis of a prospective cohort of immunocompetent hospitalized adults with community-acquired pneumonia (CAP) to determine the epidemiology, clinical features, and outcomes of pneumonia in patients with diabetes mellitus (DM). We also analyzed the risk factors for mortality and the impact of statins and other cardiovascular drugs on outcomes. Of 2407 CAP episodes, 516 (21.4%) occurred in patients with DM; 483 (97%) had type 2 diabetes, 197 (40%) were on insulin treatment, and 119 (23.9%) had end-organ damage related to DM. Patients with DM had different clinical features compared to the other patients. They were less likely to have acute onset, cough, purulent sputum, and pleural chest pain. No differences in etiology were found between study groups. Patients with DM had more inhospital acute metabolic complications, although the case-fatality rate was similar between the groups. Independent risk factors for mortality in patients with DM were advanced age, bacteremia, septic shock, and gram-negative pneumonia. Patients with end-organ damage related to DM had more inhospital cardiac events and a higher early case-fatality rate than did the overall population. The use of statins and other cardiovascular drugs was not associated with better CAP outcomes in patients with DM. In conclusion, CAP in patients with DM presents different clinical features compared to the features of patients without DM.

Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995-2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV-V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001). Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01-8.62), macrolide use (OR, 2.40; 95% CI, 1.03-5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01-8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52-23.4). In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Objectives: To determine whether prior pneumococcal and seasonal influenza vaccination improves outcomes in older adults hospitalized for community-acquired pneumonia (CAP)., Design: Prospective, observational, multicenter study., Setting: Five public hospitals providing universal free care to the whole population in three Spanish regions., Participants: Individuals aged 65 and older admitted to the hospital with CAP through the emergency department., Measurements: Pneumococcal and influenza vaccination status. The primary study outcomes were intensive care unit (ICU) admission, length of hospital stay (LOS), and overall case-fatality rate. Outcome variables of individuals vaccinated with both vaccines were compared with outcomes of those who were unvaccinated., Results: Two hundred thirty-eight individuals had received 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccination and were compared with 195 unvaccinated individuals. No differences were found with respect to combined antibiotic therapy between groups (38.0% vs 39.7%; P = .80). Similar percentages of vaccinated and unvaccinated individuals required ICU admission (7.2% vs 8.2%; P = .69). Mean LOS was significantly shorter in vaccinated individuals (9.9 vs 12.4 days; P = .04). Overall case-fatality rates were similar in both groups (5.9% vs 5.1%; P = .73). After adjustment, LOS, risk of ICU admission, and overall case-fatality rate were not associated with prior pneumococcal and seasonal influenza vaccination., Conclusion: The clinical outcomes of vaccinated older adults hospitalized with CAP were not better than those observed in unvaccinated individuals., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Background: The associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship.The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population., Methods: A total of 651 patients aged > or =65 years hospitalized due to community-acquired pneumonia through the emergency departments of five Spanish public hospitals were recruited and followed up between May 2005 and January 2007. The primary outcomes studied were: length of stay, intensive care unit admission, overall mortality and readmission. Socioeconomic status was measured using both individual and community data: occupation [categorized in six social groups (I, II, III, IVa, IVb and V)], educational level (< or = primary level or > or = secondary level) and disposable family income of the municipality or district of residence [>12,500 euro (high municipality family income) and < or =12,500 euro (low municipality family income)]. The six social groups were further categorized as upper/middle social class (groups I-IVb) and lower class (group V).Bivariate and multivariate analyses were performed. OR and their 95% confidence intervals were calculated. All statistical tests were two tailed and statistical significance was established as p < 0.05., Results: 17.7% of patients lived in a municipality or district with a high municipality family income and 63.6% were upper/middle social class (I-IVb). Only 15.7% of patients had a secondary education. The adjusted analysis showed no association between pneumonia outcomes and social class, educational level or municipality family income. However, length of stay increased significantly in patients in whom the factors, living alone and being a smoker or ex-smoker coincided (p < 0.001)., Conclusions: We measured socioeconomic status using both individual and community data and found no association between social class, educational level or municipality family income and the variables of pneumonia outcomes. The lack of differences between social classes supports the provision of universal, equitable health care by the public health system.

Background: We endeavored to construct a simple score based entirely on epidemiological and clinical variables that would stratify patients who require hospital admission because of community-acquired pneumonia into groups with a low or high risk of developing bacteremia., Methods: Derivation and internal validation cohorts were obtained by retrospective analysis of a database that included 3116 consecutive patients with community-acquired pneumonia from 2 university hospitals. Potential predictive factors were determined by means of a multivariate logistic regression equation applied to a cohort consisting of 60% of the patients. Points were assigned to significant parameters to generate the score. It was then internally validated with the remaining 40% of patients and was externally validated using an independent multicenter cohort of 1369 patients., Results: The overall rates of bacteremia were 12%-16% in the cohorts. The clinical probability estimate of developing bacteremia was based on 6 variables: liver disease, pleuritic pain, tachycardia, tachypnea, systolic hypotension, and absence of prior antibiotic treatment. For the score, 1 point was assigned to each predictive factor. In the derivation cohort, a cutoff score of 2 best identified the risk of bacteremia. In the validation cohorts, rates of bacteremia were <8% for patients with a score 1 (43%-49% of patients), whereas blood culture results were positive in 14%-63% of cases for patients with a score 2., Conclusions: This clinical score, based on readily available and objective variables, provides a useful tool to predict bacteremia. The score has been internally and externally validated and may be useful to guide diagnostic decisions for community-acquired pneumonia.

Introduction: The length of hospital stay in patients with community-acquired pneumonia (CAP) varies considerably, even though this factor has a great impact on the cost of care for this condition. The objective of this study was to identify factors associated with prolonged hospitalization in these patients (>8 days)., Methods: Observational analysis of a prospective cohort of nonimmunosuppressed adults with CAP requiring hospitalization from 1995 through 2006., Results: We documented a total of 2688 consecutive episodes of CAP. Patients who required intensive care unit admission from the emergency room (n=107), those who died during hospitalization (n=200), and patients hospitalized for more than 30 days (n=60) were excluded from the analysis. The median duration of hospital stay was 8 days (IQR, 6-11). Factors independently associated with prolonged hospital stay by stepwise multiple logistic regression analysis were advanced age (OR=1.58; 95% CI, 1.002-2.503), alcohol abuse (OR=2.07; 95% CI, 1.341-3.199), high-risk Pneumonia Severity Index class (OR=1.72; 95% CI, 1.094-2.703), aspiration pneumonia (OR=4.57; 95% CI, 1.085-19.285), pleural empyema (OR=3.73; 95% CI, 1.978-7.04), and time to clinical stability (OR=1.13; 95% CI, 1.065-1.196)., Conclusions: Several factors that were independently associated with longer hospital stay in adult patients with CAP. These factors should be considered when evaluating the adequacy of the duration of hospitalization in a specific center and when designing future studies investigating new strategies to reduce the length of hospital stay.

Background and Objective: Several sets of guidelines have advocated initial antibiotic treatment for community-acquired pneumonia due to Gram-negative bacilli in patients with specific risk factors. However, evidence to support this recommendation is scarce. We sought to identify risk factors for community-acquired pneumonia due to Gram-negative bacilli, including Pseudomonas aeruginosa, and to assess outcomes., Methods: An observational analysis was carried out on prospectively collected data for immunocompetent adults hospitalized for community-acquired pneumonia in two acute-care hospitals. Cases of pneumonia due to Gram-negative bacilli were compared with those of non-Gram-negative bacilli causes., Results: Sixty-one (2%) of 3272 episodes of community-acquired pneumonia were due to Gram-negative bacilli. COPD (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.2-5.1), current use of corticosteroids (OR 2.8, 95% CI: 1.2-6.3), prior antibiotic therapy (OR 2.6, 95% CI: 1.4-4.8), tachypnoea >or=30 cycles/min (OR 2.1, 95% CI: 1.1-4.2) and septic shock at presentation (OR 6.1, 95% CI: 2.5-14.6) were independently associated with Gram-negative bacilli pneumonia. Initial antibiotic therapy in patients with pneumonia due to Gram-negative bacilli was often inappropriate. These patients were also more likely to require admission to the intensive care unit, had longer hospital stays, and higher early (<48 h) (21% vs 2%; P < 0.001) and overall mortality (36% vs 7%; P < 0.001)., Conclusions: These results suggest that community-acquired pneumonia due to Gram-negative bacilli is uncommon, but is associated with a poor outcome. The risk factors identified in this study should be considered when selecting initial antibiotic therapy for patients with community-acquired pneumonia.

In order to analyze the characteristics of the inflammatory response occurring in blood during pneumonia, we studied 38 patients with severe community-acquired pneumonia. Venous and arterial blood samples were collected at study entry and on days 1, 2, 3, 5, and 7 after inclusion. The concentrations of proinflammatory (tumor necrosis factor alpha [TNF-alpha], interleukin 1beta [IL-1beta], IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines were determined in order to detect differences related to the origin of the sample, the causative organism, the clinical variables, and the final outcome of the episode. Legionella pneumonia infections showed higher concentrations of TNF-alpha, IL-6, IL-8, and IL-10. After 24 h, plasma IL-6, IL-8, and IL-10 concentrations in pneumococcal episodes increased, whereas in the same time interval, cytokine concentrations in Legionella episodes markedly decreased. The characteristics of the inflammatory response in bacteremic pneumococcal episodes were different from those in nonbacteremic episodes, as indicated by the higher plasma cytokine concentrations in the former group. Finally, our analysis of cytokine concentrations with regard to the outcome--in terms of the need for intensive care unit admittance and/or mechanical ventilation as well as mortality--suggests that there is a direct relationship between the intensity of the inflammatory response measured in blood and the severity of the episode.

This prospective case-control study sought to identify differences in presentation between Legionella pneumonia (LP) diagnosed by urinary antigen and bacteremic pneumococcal pneumonia (PP), with the aim of assessing the ability of physicians to recognize such differences at admission and validating the Community-Based Pneumonia Incidence Study (CBPIS) Group scoring system for LP diagnosis. Significant differences in presentation were found: male sex, previous receipt of beta-lactam therapy, and temperature >39 degrees C were positively associated with LP; purulent sputum, pleuritic chest pain, and previous upper respiratory tract infection were negatively associated with LP. Physicians considered Legionella to be the most likely diagnosis in 52 (64%) of 81 LP cases and in 8 (6%) of 136 PP cases. Initial administration of a macrolide and rifampin and requests for urinary antigen testing for Legionella at admission were significantly more frequent among patients with LP. Overall, the CBPIS score did not differentiate reliably between LP and PP. Although certain presenting clinical features may allow recognition of LP, it is difficult to express them in a reliable scoring system.

Background: Early failure is a matter of great concern in the treatment of community-acquired pneumonia. However, information on its causes and risk factors is lacking. Methods: Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia. Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedures. Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis. Results: At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy. Eighty-one patients (6%) had early failure. The main causes of early failure were progressive pneumonia (n = 54), pleural empyema (n = 18), lack of response (n = 13), and uncontrolled sepsis (n = 9). Independent factors associated with early failure were older age (>65 years) (odds ratio [OR], 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51). Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both). Conclusions: Early failure is infrequent but is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Most cases occur because of inadequate host-pathogen responses. Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines. [ABSTRACT FROM AUTHOR]