Antonella Simonetti

Prognostic value of serum albumin levels in hospitalized adults with community-acquired pneumonia

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.

Rainfall is a risk factor for sporadic cases of Legionella pneumophila pneumonia.

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/m2 in the Legionella pneumonia group vs. 0.328 liters/m2 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.

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

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.

Biomarkers for predicting short-term mortality in community-acquired pneumonia: A systematic review and meta-analysis

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.

Clinical Features, Etiology and Outcomes of Community-Acquired Pneumonia in Patients with Chronic Obstructive Pulmonary Disease

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.

Prediction of prognosis by markers in community-acquired pneumonia

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.

Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal 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 (<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.

Solithromycin for the treatment of community-acquired bacterial pneumonia.

ABSTRACT 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.

Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single centre prospective cohort study.

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post‐transplant over the last 10‐year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (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 (40.5–2.2%). In contrast, there was a steady increase in Gram‐negative bacilli (GNB) BSI (54.1–93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4–20.4%) and Klebsiella pneumoniae (7.1–26.5%). Multidrug‐resistant (MDR) GNB (4.8–38.8%; P < 0.001) rose dramatically, especially due to extended‐spectrum β‐lactamase (ESBL) production (7.1–34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9–55.3%; P < 0.001) and as targeted antibiotic treatment (11.9–46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL‐producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time.

Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial

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