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      C-reactive protein and procalcitonin to discriminate between tuberculosis, Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV-infected inpatients meeting WHO criteria for seriously ill: a prospective cohort study

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          Abstract

          Background

          Tuberculosis, bacterial community-acquired pneumonia (CAP), and Pneumocystis jirovecii pneumonia (PJP) are the three commonest causes of hospitalisation in HIV-infected adults. Prompt diagnosis and treatment initiation are important to reduce morbidity and mortality, but are hampered by limited diagnostic resources in resource poor settings. C-reactive protein (CRP) and procalcitonin have shown diagnostic utility for respiratory tract infections, however few studies have focussed on their ability to distinguish between tuberculosis, CAP, and PJP in HIV-infected inpatients.

          Methods

          We evaluated the diagnostic accuracy of CRP and procalcitonin, compared with composite reference standards, to discriminate between the three target infections in adult HIV-infected inpatients in two district level hospitals in Cape Town, South Africa. Participants were admitted with current cough and danger signs in accordance with the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study clinicians were blinded to CRP and procalcitonin results.

          Results

          Two hundred forty-eight participants met study case definitions: 133 with tuberculosis, 61 with CAP, 16 with PJP, and 38 with mixed infection. In the 210 particpants with single infections the differences in median CRP and procalcitonin concentrations between the three infections were statistically significant, but distributions overlapped considerably. CRP and procalcitonin concentrations were highest in the CAP group and lowest in the PJP group. CRP and procalcitonin cut-offs with sensitivities of ≥90% were found for all three target infection pairs, but corresponding specificities were low. Highest receiver operating characteristic areas under the curve for CRP and procalcitonin were for PJP versus tuberculosis and PJP versus CAP (0.68 and 0.71, and 0.74 and 0.69 respectively).

          Conclusions

          CRP and procalcitonin showed limited value in discriminating between the three target infections due to widely overlapping distributions, but diagnostic accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings show limitations for CRP and procalcitonin, particularly for discriminiation of tuberculosis form CAP, however they may have greater diagnostic utility as part of a panel of biomarkers or in clinical prediction rules.

          Electronic supplementary material

          The online version of this article (10.1186/s12879-018-3303-6) contains supplementary material, which is available to authorized users.

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          Most cited references22

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          STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies

          Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting Diagnostic Accuracy (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
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            Classification accuracy and cut point selection.

            Xinhua Liu (2012)
            In biomedical research and practice, quantitative tests or biomarkers are often used for diagnostic or screening purposes, with a cut point established on the quantitative measurement to aid binary classification. This paper introduces an alternative to the traditional methods based on the Youden index and the closest-to-(0, 1) criterion for threshold selection. A concordance probability evaluating the classification accuracy of a dichotomized measure is defined as an objective function of the possible cut point. A nonparametric approach is used to search for the optimal cut point maximizing the objective function. The procedure is shown to perform well in a simulation study. Using data from a real-world study of arsenic-induced skin lesions, we apply the method to a measure of blood arsenic levels, selecting a cut point to be used as a warning threshold. Copyright © 2012 John Wiley & Sons, Ltd.
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              Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms.

              Previous randomized controlled trials suggest that using clinical algorithms based on procalcitonin levels, a marker of bacterial infections, results in reduced antibiotic use without a deleterious effect on clinical outcomes. However, algorithms differed among trials and were embedded primarily within the European health care setting. Herein, we summarize the design, efficacy, and safety of previous randomized controlled trials and propose adapted algorithms for US settings. We performed a systematic search and included all 14 randomized controlled trials (N = 4467 patients) that investigated procalcitonin algorithms for antibiotic treatment decisions in adult patients with respiratory tract infections and sepsis from primary care, emergency department (ED), and intensive care unit settings. We found no significant difference in mortality between procalcitonin-treated and control patients overall (odds ratio, 0.91; 95% confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED (0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings individually. A consistent reduction was observed in antibiotic prescription and/or duration of therapy, mainly owing to lower prescribing rates in low-acuity primary care and ED patients, and shorter duration of therapy in moderate- and high-acuity ED and intensive care unit patients. Measurement of procalcitonin levels for antibiotic decisions in patients with respiratory tract infections and sepsis appears to reduce antibiotic exposure without worsening the mortality rate. We propose specific procalcitonin algorithms for low-, moderate-, and high-acuity patients as a basis for future trials aiming at reducing antibiotic overconsumption.
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                Author and article information

                Contributors
                marcfiona1@gmail.com
                GRSRUL001@myuct.ac.za
                Nicki.Tiffin@uct.ac.za
                mxrangaka@yahoo.co.uk
                andrew.boulle@uct.ac.za
                marc.mendelson@uct.ac.za
                +27-21-4066286 , gary.maartens@uct.ac.za
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                14 August 2018
                14 August 2018
                2018
                : 18
                : 399
                Affiliations
                [1 ]ISNI 0000 0004 1937 1151, GRID grid.7836.a, School of Public Health and Family Medicine, , University of Cape Town, ; Cape Town, South Africa
                [2 ]ISNI 0000 0004 1937 1151, GRID grid.7836.a, Division of Clinical Pharmacology, Department of Medicine, , University of Cape Town, ; Cape Town, South Africa
                [3 ]ISNI 0000 0004 1937 1151, GRID grid.7836.a, Centre for Infectious Diseases Research Initiative, Institute of Infectious Diseases & Molecular Medicine, , University of Cape Town, ; Cape Town, South Africa
                [4 ]ISNI 0000000121901201, GRID grid.83440.3b, Department of Infection & Population Health, Institute of Global Health, , University College London, ; London, UK
                [5 ]ISNI 0000 0004 1937 1151, GRID grid.7836.a, Department of Medicine, , University of Cape Town, ; Cape Town, South Africa
                [6 ]ISNI 0000 0004 1937 1151, GRID grid.7836.a, Division of Infectious Diseases and HIV Medicine, Department of Medicine, , University of Cape Town, ; Cape Town, South Africa
                Author information
                http://orcid.org/0000-0003-3080-6606
                Article
                3303
                10.1186/s12879-018-3303-6
                6092834
                30107791
                9847dbad-d2d8-4051-b327-6e907bde2209
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 March 2018
                : 1 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R01 AI 96735-01
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                hiv,tuberculosis,bacterial community-acquired pneumonia,pneumocystis jirovecii pneumonia,c-reactive protein,procalcitonin,diagnostic accuracy,who algorithm

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