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      Clinical review: The role of biomarkers in the diagnosis and management of community-acquired pneumonia

      review-article
      1 , , 2
      Critical Care
      BioMed Central

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          Abstract

          In patients with community-acquired pneumonia, traditional criteria of infection based on clinical signs and symptoms, clinical scoring systems, and general inflammatory indicators (for example, leukocytosis, fever, C-reactive protein and blood cultures) are often of limited clinical value and remain an unreliable guide to etiology, optimal therapy and prognosis. Procalcitonin is superior to other commonly used markers in its specificity for bacterial infection (allowing alternative diagnoses to be excluded), as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy. It can therefore be viewed as a diagnostic, prognostic, and perhaps even theragnostic test. It more closely matches the criteria for usefulness than other candidate biomarkers such as C-reactive protein, which is rather a nonspecific marker of acute phase inflammation, and proinflammatory cytokines such as plasma IL-6 levels that are highly variable, cumbersome to measure, and lack specificity for systemic infection. Elevated levels of pro-adrenomedullin, copeptin (which is produced in equimolar amounts to vasopressin), natriuretic peptides and cortisol are significantly related to mortality in community-acquired pneumonia, as are other prohormones such as pro-atrial natriuretic peptide, coagulation markers, and other combinations of inflammatory cytokine profiles. However, all biomarkers have weaknesses as well as strengths. None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient.

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          Most cited references72

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          A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria.

          To validate scoring algorithm criteria established by the Japanese Association for Acute Medicine (JAAM) for disseminated intravascular coagulation (DIC) and to evaluate its diagnostic property by comparing the two leading scoring systems for DIC, from the Japanese Ministry of Health and Welfare (JMHW) and International Society on Thrombosis and Haemostasis (ISTH). Prospective, multicenter study during a 3-month period. General critical care center in a tertiary care hospital. Two hundred seventy-three patients with platelet counts<150x109/L were enrolled. None. The JAAM, JMHW, and ISTH DIC scoring algorithms were prospectively applied within 12 hrs of patients meeting the inclusion criteria (day 0) to days 1-3, by global coagulation tests. The numbers of systemic inflammatory response syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) scores were determined simultaneously. Mortality associated with any cause was also assessed 28 days after the enrollment. All global coagulation tests and SIRS criteria adopted in the JAAM criteria and their cutoff points were validated with use of SOFA scores and mortality rate. DIC diagnostic rate of the JAAM DIC scoring system was significantly higher than that of the other two criteria (p<.001). The JAAM DIC algorithm was the most sensitive for early diagnosis of DIC (p<.001). PATIENTS who fulfilled the JAAM DIC criteria included almost all those whose DIC was diagnosed by the JMHW and ISTH scoring systems. The JAAM DIC scores showed significant correlation with SOFA scores ([rho]=0.499; p<.001). SOFA score and mortality rate worsened in accordance with an increase in the JAAM DIC score. Fibrinogen criteria had little effect in predicting outcome for the DIC patients, and a total score of 4 points in the JAAM scoring system without fibrinogen was closely related to poor prognosis. According to the results, we revised the JAAM criteria by excluding fibrinogen and confirmed that the DIC diagnostic properties of original criteria remained unchanged in the revised JAAM criteria. The JAAM scoring system has an acceptable property for the diagnosis of DIC. The scoring system identified most of the patients diagnosed by the JMHW and ISTH criteria. Revised JAAM DIC criteria preserved all properties of the original criteria for DIC diagnosis. The revised scoring system can be useful for selecting DIC patients for early treatment in a critical care setting.
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            Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis.

            Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.
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              Pyogenic bacterial infections in humans with MyD88 deficiency.

              MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2010
                8 February 2010
                8 February 2011
                : 14
                : 1
                : 203
                Affiliations
                [1 ]Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
                [2 ]Warren Alpert Medical School of Brown University, Infectious Disease Division, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
                Article
                cc8155
                10.1186/cc8155
                2875480
                20236471
                c98680fd-4a51-4f48-859d-6f65bf056894
                Copyright ©2010 BioMed Central Ltd
                History
                Categories
                Review

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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