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The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia.Observational study conducted during the first (March-April 2020), second (October-November 2020), third (January-February 2021), and fourth wave (July-August 2021) of COVID-19 in five centers of Catalonia. All subjects were adults ( 18 years old) hospitalized with a proven SARS-CoV-2 infection and with therapeutic ceiling of care assessed by the attending physician at hospital admission.A total of 5813 subjects were analyzed. Subjects with a ceiling of care were mainly older (difference in median age of 20 years), with more comorbidities (Charlson index 3 points higher) and with fewer clinical signs at baseline than patients without a ceiling of care. Some features of their clinical profiles changed among waves. There were differences in treatments received during hospital admission across waves, but not between subjects with and without a ceiling of care. Subjects with a ceiling of care had a death incidence more than four times the death incidence of subjects a without a ceiling of care (risk ratio (RR) ranging from 3.5 in the first wave to almost 6 in the third and fourth). Incidence of severe pneumonia and complications for subjects with a ceiling of care was around 1.5 times the incidence in subjects without a ceiling of care.Analysis of hospitalized subjects with SARS-CoV-2 infection should be stratified according to therapeutic ceiling of care to avoid bias and outcome misestimation.

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein–protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

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 leukocyte antigen DR (mHLA-DR) expression. Results In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumor 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.

Background: 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 comorbidities and age 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 leukocyte antigen DR (mHLA-DR) expression.Results: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumor 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. These findings suggest that age and comorbidities have much more of an impact than to simply reduce physiological reserve and can cause variations in the inflammatory response in CAP.

To analyse trends in the aetiology, treatment and outcomes of BSI within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in SOT recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5% to 2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1% to 93.3%; p

Little is known about the sensitivity of the BinaxNOW pneumococcal urinary antigen (PUA) test for adult pneumococcal pneumonia caused by different serotypes. In this study, we aimed to analyze the trends in the sensitivity of the PUA test over a 15-year period (2001 to 2015) and to analyze its sensitivity for pneumococcal pneumonia caused by different serotypes. In total, we analyzed 1,096 pneumococcal isolates from adults with pneumococcal pneumonia who had a PUA test performed at the onset of the episode. Three periods were analyzed: 2001 to 2005 (early use of the seven-valent pneumococcal conjugate vaccine [early PCV7]), 2006 to 2010 (late PCV7), and 2011 to 2015 (early PCV13). The sensitivity of the PUA test varied from 76.4% (95% confidence interval [CI], 70.5% to 82.4%) in the period from 2001 to 2005 to 77.9% in 2006 to 2010 (95% CI, 74.4% to 81.4%) and decreased to 60.5% (95% CI, 55.4% to 65.6%) in 2011 to 2015. This decrease was observed in 560 proven (83.2% in 2001 to 2005, 86.5% in 2006 to 2010, and 78.1%) and 536 probable (70.0% in 2001 to 2005, 68.7% in 2006 to 2010, and 41.5% in 2011 to 2015) episodes of pneumococcal pneumonia. Differences were observed in the sensitivity of the PUA test for diagnosing pneumonia caused by certain serotypes, being highest for the 9V (90.6%), 14 (86.8%), 18C (100%), and 20 (100%) serotypes and lowest for the 8 (55.2%), 9L/N (39.1%), 11A (48.8%), 23B (33.3%), and nontypeable (47.8%) serotypes. Comparing 2001 to 2005, 2006 to 2010, and 2011 to 2015, the prevalence of serotypes 9V (3.1%, 3.7%, and 1.7%, respectively) and 14 (7.2%, 5.1%, and 3.1%, respectively) decreased, while the prevalence of serotypes 23B (0%, 0.7%, and 1.4%, respectively), 9L/N (1.0%, 1.6%, and 3.4%, respectively), 11A (2.6%, 4.2%, and 3.7%, respectively), and 8 (1.5%, 1.5%, and 5.1%, respectively) increased. The PUA test sensitivity varied by pneumococcal pneumonia serotype, and these differences and the changes in serotype distribution were associated with an overall decrease in the sensitivity of the PUA test.

To investigate whether serum albumin levels within 24 h of admission correlate with outcomes in community-acquired pneumonia (CAP).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.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.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.

Recent changes in the management of patients with haematological malignancies might have influenced the aetiology, characteristics, antimicrobial resistance and outcomes of bloodstream infection (BSI) during neutropenia. We compared 272 episodes of BSI in adult neutropenic patients with cancer prospectively collected from January 1991 to December 1996 (first period), when quinolone prophylaxis was used, with 283 episodes recorded from January 2006 to March 2010 (second period), when antibacterial prophylaxis was stopped. Patients in the second period were significantly older and were more likely to have graft-versus-host disease and a urinary catheter in place, whereas the presence of a central venous catheter, parenteral nutrition, corticosteroids and antifungal and quinolone prophylaxis, were more frequent in the first period. More patients in the first period had mucositis and soft-tissue infection as the origin of BSI, but an endogenous source was more common during the second. Gram-positive BSI was more frequent in the first period (64% versus 41%; p

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.

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 (

Resumen Fundamento y objetivo Describir nuestra cohorte de pacientes con nefritis lupica mesangial proliferativa y su seguimiento a largo plazo, con especial atencion a los factores de mal pronostico. Pacientes y metodo Se evaluaron 27 pacientes de forma retrospectiva y controlados en el Servicio de Medicina Interna del Hospital Universitario de Bellvitge entre 1974 y 2010. Se realizo un control al ano, a los 3 y a los 5 anos de la biopsia. Resultados Habia 22 mujeres (81,5%), con una edad media (DE) en el momento del diagnostico de la nefritis de 34,83 (13,45) anos. Al ano de la biopsia 21 pacientes habian alcanzado la remision parcial o completa (80,77%) y a los 5 anos de control 21 pacientes (77,77%) estaban en remision. Cuatro pacientes sufrieron transformacion a otra clase histologica. Recidivaron 7 pacientes (29,63%). En estos 36 anos de seguimiento fallecieron 7 pacientes, 3 de ellos por causas relacionadas con el lupus eritematoso sistemico. Conclusiones El factor pronostico mas claramente relacionado con una mala respuesta es el inicio de la nefritis por encima de los 45 anos, por lo que se deberia valorar el uso de inmunodepresores de entrada asociados a glucocorticoides en estos pacientes.

Summary 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.

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 The trial was supported by the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, by the European Development Regional Fund “A Way to Achieve Europe”, the Spanish Network for Research in Infectious Diseases (REIPI RD06/0008), the Fondo de Investigación Sanitaria de la Seguridad Social (grant 07/0864), and the Institut d’Investigació Biomèdica de Bellvitge. The sponsors had no role in the study design, collection, analysis, or interpretation of data or in the decision to submit the manuscript for publication.

Objectives It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines. Setting A tertiary teaching hospital in Barcelona, Spain. Participants Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group). Intervention Patients were randomly assigned to receive 20 mg of simvastatin or placebo administered in the first 24 h of hospital admission and once daily thereafter for 4 days. Outcome Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment administration. Results The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3 days, IQR 2–5 vs 3 days, IQR 2–5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-α (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08 and 0.53, respectively). Conclusions Our results suggest that the use of simvastatin, 20 mg once daily for 4 days, since hospital admission did not reduce the time to clinical stability and the levels of inflammatory cytokines in hospitalised patients with CAP. Trial registration number ISRCTN91327214.

Community-acquired pneumonia (CAP) is an increasing problem among the elderly. Multiple factors related to ageing, such as comorbidities, nutritional status and swallowing dysfunction have been implicated in the increased incidence of CAP in the older population. Moreover, mortality in patients with CAP rises dramatically with increasing age. Streptococcus pneumoniae is still the most common pathogen among the elderly, although CAP may also be caused by drug-resistant microorganisms and aspiration pneumonia. Furthermore, in the elderly CAP has a different clinical presentation, often lacking the typical acute symptoms observed in younger adults, due to the lower local and systemic inflammatory response. Several independent prognostic factors for mortality in the elderly have been identified, including factors related to pneumonia severity, inadequate response to infection, and low functional status. CAP scores and biomarkers have lower prognostic value in the elderly, and so there is a need to find new scales or to set new cut-off points for current scores in this population. Adherence to the current guidelines for CAP has a significant beneficial impact on clinical outcomes in elderly patients. Particular attention should also be paid to nutritional status, fluid administration, functional status, and comorbidity stabilizing therapy in this group of frail patients. This article presents an up-to-date review of the main aspects of CAP in elderly patients, including epidemiology, causative organisms, clinical features, and prognosis, and assesses key points for best practices for the management of the disease.

Information on the influence of pre-hospital antibiotic treatment on the causative organisms, clinical features and outcomes of patients with community-acquired pneumonia (CAP) remains scarce. We performed an observational study of a prospective cohort of non-immunosuppressed adults hospitalized with CAP between 2003 and 2012. Patients were divided into two groups: those who had received pre-hospital antibiotic treatment for the same episode of CAP and those who had not. A propensity score was used to match patients. Of 2179 consecutive episodes of CAP, 376 (17.3%) occurred in patients who had received pre-hospital antibiotic treatment. After propensity score matching, Legionella pneumophila was more frequently identified in patients with pre-hospital antibiotic treatment, while Streptococcus pneumoniae was less common (p

It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011). Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5%) had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases), antigenuria (206) and serology (98). Daily rainfall average was 0.556 liters/m(2) in the Legionella pneumonia group vs. 0.328 liters/m(2) for non-Legionella pneumonia cases (p = 0.04). A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54). Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03). Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003). No relationship was found between rainfall average and non-Legionella pneumonia cases (-0.06; p = 0.24). As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall.

Little information is available on the changes over time in community-acquired pneumonia (CAP) management and their impact on 30-day mortality in hospitalized patients. We performed a prospective, observational study of non-severely immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558 patients were included. Thirty-day mortality decreased from 9.6% in the first study period (1995–99) to 4.1% in the last period (2010–14); with a progressive downward trend (–0.2% death/year; p for trend = 0.003). Over time, patients were older (p 0.02), had more co-morbidities (p 0.037), more frequently presented severe illness according to the Pneumonia Severity Index (p

The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p

The evaluation of tests for neonatal sepsis is important because the infection may present a very serious threat to the baby. There is an urgent need to know whether the baby has sepsis to institute treatment as quickly as possible. Confirmation of the diagnosis may take time, and diagnostic tests are used to obtain a rapid indication of the infection status. These tests are not perfect. Some real cases of infection will produce negative test results, whereas some babies without infection will test positive. The potential usefulness of the test will depend, above all, on the clinical condition of the baby. If the baby is really very sick, the test will not give very much additional information. Similarly, if the baby is evidently well, a clinical examination will be sufficient and a positive test result would not dramatically increase the probability that the baby is infected. It is in situations in which the clinical picture leaves the physician in doubt about the infection status that a diagnostic test is likely to be most useful. Thus, the result of a diagnostic test must be evaluated in the light of the clinical condition of the baby. Extensive literature exists on single laboratory tests or combinations of tests, as well as tests used together with risk factors and/or clinical signs, to diagnose neonatal sepsis. In many instances, the results of the evaluations have been conflicting. There are several possible explanations for the divergent results, and the purpose of this review is to update readers on the topic and raise issues that should be addressed in the future. Throughout pregnancy and until the membranes rupture, the fetus is relatively protected from the microbial flora of the mother by the chorioamniotic membranes, the placenta, and poorly understood antibacterial factors in amniotic fluid (1). However, there …

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.