adrenomedullin and Pneumonia--Bacterial

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.

Topics: Adrenomedullin; Biomarkers; C-Reactive Protein; Calcitonin; Community-Acquired Infections; Cytokines; Fibrin Fibrinogen Degradation Products; Humans; Intensive Care Units; Pneumonia, Bacterial; Prognosis; Protein Precursors; Risk Factors; Severity of Illness Index; Survival Analysis

Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term "hormokine" encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.

Topics: Adrenomedullin; Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Pathways; Diagnosis, Differential; Glycopeptides; Humans; Natriuretic Peptides; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Protein Precursors; Respiratory Tract Infections; Sepsis

The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) is not well established. The aim of this study was to assess the impact of reducing the duration of antibiotic treatment on long-term prognosis in patients hospitalized with CAP.. This was a multicenter study assessing complications developed during 1 year of patients previously hospitalized with CAP who had been included in a randomized clinical trial concerning the duration of antibiotic treatment. Mortality at 90 days, at 180 days and at 1 year was analyzed, as well as new admissions and cardiovascular complications. A subanalysis was carried out in one of the hospitals by measuring C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) at admission, at day 5 and at day 30.. A total of 312 patients were included, 150 in the control group and 162 in the intervention group. Ninety day, 180 day and 1-year mortality in the per-protocol analysis were 8 (2.57%), 10 (3.22%) and 14 (4.50%), respectively. There were no significant differences between both groups in terms of 1-year mortality (p = 0.94), new admissions (p = 0.84) or cardiovascular events (p = 0.33). No differences were observed between biomarker level differences from day 5 to day 30 (CRP p = 0.29; PCT p = 0.44; proADM p = 0.52).. Reducing antibiotic treatment in hospitalized patients with CAP based on clinical stability criteria is safe, without leading to a greater number of long-term complications.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Community-Acquired Infections; Drug Administration Schedule; Female; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Pneumonia, Bacterial; Procalcitonin; Prognosis; Protein Precursors; Severity of Illness Index; Spain; Time Factors

Community-acquired-pneumonia is the leading cause of child mortality worldwide. Very few studies have explored the predictive value of Proadrenomedullin and Copeptin in pediatric severe pneumonia and bacteremia.. Proadrenomedullin and Copeptin were assessed as predictors for complicated community-acquired pneumonia (bacteremia, empyema) in 88 children aged 0 to 16 years presenting to the pediatric emergency department, using B.R.A.H.M.S. Kryptor Compact pro-ADM and Copeptin with the TRACE technology (time-resolved amplified cryptase emission). STARD standard reporting was used.. A complicated community-acquired pneumonia was found in 11 out of 88 children (12.5 %). Proadrenomedullin median values increased more than twofold, in complicated vs. uncomplicated (0.18 vs. 0.08 nmol/L, p = 0.039), and fivefold in bacteremic vs. non-bacteremic pneumonia (0.40 vs. 0.08 nmol/L, p = 0.02). Proadrenomedullin > 0.16 nmol/L showed 100 % sensitivity (95 % CI 39.8 - 100.0) and 70 % (95 % CI 58.7 - 79.7) specificity for bacteremia. Copeptin showed no added-value.. Proadrenomedullin seems a reliable and available predictor for complicated CAP, and could therefore help the physician with the decision to hospitalize, and choose the antibiotics administration route. Larger studies are needed.

Topics: Adolescent; Adrenomedullin; Bacteremia; Biomarkers; Child; Child, Preschool; Cohort Studies; Community-Acquired Infections; Emergency Service, Hospital; Empyema, Pleural; Female; Glycopeptides; Humans; Infant; Infant, Newborn; Logistic Models; Male; Pneumonia, Bacterial; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.

Topics: Adrenomedullin; Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Confusion; Female; Humans; Male; Middle Aged; Peptide Fragments; Pneumonia, Bacterial; Pneumonia, Viral; Prognosis; Prospective Studies; Protein Precursors; Respiratory Rate; Severity of Illness Index; Smoking; Urea

Midregional proadrenomedullin (proADM) is a novel biomarker with potential prognostic utility in patients with community-acquired pneumonia. The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in severe sepsis and septic shock due to CAP.. Prospective observational study including 49 patients admitted to ICU with both a clinical and radiologic diagnosis of pneumonia and fulfilling criteria for severe sepsis or septic shock. The prognostic accuracy of proADM levels was compared with those of pneumonia severity index and of procalcitonin (PCT) and C-reactive protein (CRP).. 49 patients with severe sepsis or septic shock due to CAP were included in the study. Mortality was 24.5% for ICU and 34.7% for hospital mortality. In all cases proADM values at ICU admission were pathological (considering normal proADM levels <4 nmol/L). ProADM consistently rose as PSI class advanced from II to V (p = 0.02). Median proADM levels were higher (p <0.01) in hospital non-survivors 5.0 (1.9-10.1) nmol/L vs. survivors 1.7 (1.3-3.1) nmol/L. These differences were also significant with respect to ICU mortality. The receiver-operating characteristic curve for proADM yielded an AUC of 0.72; better than the AUC for PCT and CRP (0.40 and 0.44 respectively) and similar to PSI (0.74).. In our study MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients.

Topics: Adrenomedullin; Biomarkers; Community-Acquired Infections; Female; Follow-Up Studies; Humans; Immunoassay; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Reproducibility of Results; Severity of Illness Index; Shock, Septic

Topics: Adrenomedullin; Community-Acquired Infections; Female; Humans; Male; Pneumonia, Bacterial; Pneumonia, Viral; Protein Precursors