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      Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study

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          Abstract

          Introduction

          Community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission remains a severe medical condition, presenting ICU mortality rates reaching 30%. The aim of this study was to assess the value of different patterns of C-reactive protein (CRP)-ratio response to antibiotic therapy in patients with severe CAP requiring ICU admission as an early maker of outcome.

          Methods

          In total, 191 patients with severe CAP were prospectively included and CRP was sampled every other day from D1 to D7 of antibiotic prescription. CRP-ratio was calculated in relation to D1 CRP concentration. Patients were classified according to an individual pattern of CRP-ratio response with the following criteria: fast response - when D5 CRP was less than or equal to 0.4 of D1 CRP concentration; slow response - when D5 CRP was > 0.4 and D7 less than or equal to 0.8 of D1 CRP concentration; nonresponse - when D7 CRP was > 0.8 of D1 CRP concentration. Comparison between ICU survivors and non-survivors was performed.

          Results

          CRP-ratio from D1 to D7 decreased faster in survivors than in non-survivors (p = 0.01). The ability of CRP-ratio by D5 to predict ICU outcome assessed by the area under the ROC curve was 0.73 (95% Confidence Interval, 0.64 - 0.82). By D5, a CRP concentration above 0.5 of the initial level was a marker of poor outcome (sensitivity 0.81, specificity 0.58, positive likelihood ratio 1.93, negative likelihood ratio 0.33). The time-dependent analysis of CRP-ratio of the three patterns (fast response n = 66; slow response n = 81; nonresponse n = 44) was significantly different between groups (p < 0.001). The ICU mortality rate was considerably different according to the patterns of CRP-ratio response: fast response 4.8%, slow response 17.3% and nonresponse 36.4% (p < 0.001).

          Conclusions

          In severe CAP, sequential evaluation of CRP-ratio was useful in the early identification of patients with poor outcome. The evaluation of CRP-ratio pattern of response to antibiotics during the first week of therapy was useful in the recognition of the individual clinical evolution.

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          Most cited references16

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          Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis.

          To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. The overall mortality for the 33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with mortality using both summary ORs and RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95% CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR = 2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9), bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.
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            Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease.

            Plasma and whole-body turnover studies of human C-reactive protein (CRP), isolated from a single normal healthy donor and labeled with 125I, were undertaken in 8 healthy control subjects and 35 hospitalized patients including cases of rheumatoid arthritis, systemic lupus erythematosus, infections, and neoplasia. Plasma clearance of 125I-CRP closely approximated to a monoexponential function and was similar in the control and all patient groups. There was no evidence for accelerated clearance or catabolism of CRP in any of the diseases studied. The 19-h half-life was more rapid than that of most human plasma proteins studied previously, and the fractional catabolic rate was independent of the plasma CRP concentration. The synthesis rate of CRP is thus the only significant determinant of its plasma level, confirming the validity of serum CRP measurement as an objective index of disease activity in disorders associated with an acute-phase response. Approximately 90% of injected radioactivity was recovered in the urine after 7 d, and scintigraphic imaging studies with 123I-labeled CRP in 10 patients with different focal pathology showed no significant localization of tracer. The functions of CRP are thus likely to be effected predominantly in the fluid phase rather than by major deposition at sites of tissue damage or inflammation.
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              Epidemiology of community-acquired pneumonia in adults: a population-based study.

              In this prospective study, the authors assessed the incidence, aetiology, and outcome of patients with community-acquired pneumonia in the general population. From December 1993 to November 1995, a study was performed in a mixed residential-industrial urban population of the "Maresme" region in Barcelona, Spain. All subjects > or =14 yrs of age (annual average population size 74,368 inhabitants) with clinically suspected community-acquired pneumonia were registered. All cases were re-evaluated by chest radiographs on the 5th day of illness and at monthly intervals until complete recovery. Urine and blood samples were obtained for culture and antigen detection. When lower respiratory tract secretions were obtained, these were also cultured. There were 241 patients with community-acquired pneumonia, with an annual incidence rate of 1.62 cases (95% confidence interval, 1.42-1.82) per 1,000 inhabitants. Incidence rates increased by age groups and were higher in males than in females. Of 232 patients with aetiological data, 104 had an identifiable aetiology. A total of 114 pathogens were found (single pathogen 94, two pathogens 10). There were 81 episodes of bacterial infection and 33 of viral infection. The most common pathogens were Streptococcus pneumoniae, Chlamydia pneumoniae, and influenza A and B viruses. No case of Hantavirus infection was found. The rate of hospital admission was 61.4% with a mean+/-SD length of 11.7+/-10.1 days, a mean period of 23.0+/-14.3 days inactivity, and an overall mortality rate of 5%. The high rate of hospital admission, prolonged stay in hospital, and long period of inactivity all continue to constitute a social and health care burden of community-acquired pneumonia.
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                Author and article information

                Contributors
                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2012
                26 March 2012
                : 16
                : 2
                : R53
                Affiliations
                [1 ]Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal (Hospital de São Francisco Xavier, CHLO, Estrada do Forte do Alto do Duque, 1449-005 Lisbon, Portugal
                [2 ]CEDOC, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal (Campo dos Mártires da Pátria, 130 1169-056 Lisboa
                [3 ]D'Or Institute for Research and Education, Rio de Janeiro, Brazil (Rua Diniz Cordeiro, n° 30 - Botafogo/RJ 22281-100 - Brasil
                [4 ]Postgraduate Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil (Rua Riachuelo, 172 - Centro, Rio de Janeiro - RJ, 20230-014, Brasil
                [5 ]Instituto de Pesquisa Clínica Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil (Avenida Brasil, 4365, Manguinhos - Rio de Janeiro - RJ, 21040-360, Brasil
                [6 ]Intensive Care Unit, Hospital Barra D'Or, Rio de Janeiro, Brazil (Avenida Ayrton Senna, 2541 - Barra da Tijuca, Rio de Janeiro - RJ, 22775-002, Brasil
                [7 ]Laboratory of Immunopharmacology, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil (Avenida Brasil, 4365, Manguinhos - Rio de Janeiro - RJ, 21040-360, Brasil
                [8 ]Pulmonary Diseases Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (Ilha Cidade Universitária - Cidade Universitária, Rio de Janeiro - RJ, 21941-970, Brasil
                Article
                cc11291
                10.1186/cc11291
                3681380
                22449513
                f74809a1-b5cb-492b-80b4-ef87f3c9b2c0
                Copyright ©2011 Coelho et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 October 2011
                : 2 February 2012
                : 26 March 2012
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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