Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan

Josselin Le Bel, Pierre Hausfater, Camille Chenevier-Gobeaux, François-Xavier Blanc, Mikhael Benjoar, Cécile Ficko, Patrick Ray, Christophe Choquet, Xavier Duval, Yann-Erick Claessens, ESCAPED study group, Y E Claessens, X Duval, E Bouvard, M F Carette, M P Debray, C Mayaud, C Leport, N Houhou, S Tubiana, M Benjoar, F X Blanc, A L Brun, L Epelboin, C Ficko, A Khalil, H Lefloch, J M Naccache, B Rammaert, A Abry, J C Allo, S Andre, C Andreotti, N Baarir, M Bendahou, L Benlafia, J Bernard, A Berthoumieu, M E Billemont, J Bokobza, A L Brun, E Burggraff, P Canavaggio, M F Carette, E Casalino, S Castro, C Choquet, H Clément, L Colosi, A Dabreteau, S Damelincourt, S Dautheville, M P Debray, M Delay, S Delerme, L Depierre, F Djamouri, F Dumas, M R S Fadel, A Feydey, Y Freund, L Garcia, H Goulet, P Hausfater, E Ilic-Habensus, M O Josse, J Kansao, Y Kieffer, F Lecomte, K Lemkarane, P Madonna, O Meyniard, L Mzabi, D Pariente, J Pernet, F Perruche, J M Piquet, R Ranerison, P Ray, F Renai, E Rouff, D Saget, K Saïdi, G Sauvin, E Trabattoni, N Trimech, C Auger, B Pasquet, S Tamazirt, J M Treluyer, F Tubach, J Wang, Josselin Le Bel, Pierre Hausfater, Camille Chenevier-Gobeaux, François-Xavier Blanc, Mikhael Benjoar, Cécile Ficko, Patrick Ray, Christophe Choquet, Xavier Duval, Yann-Erick Claessens, ESCAPED study group, Y E Claessens, X Duval, E Bouvard, M F Carette, M P Debray, C Mayaud, C Leport, N Houhou, S Tubiana, M Benjoar, F X Blanc, A L Brun, L Epelboin, C Ficko, A Khalil, H Lefloch, J M Naccache, B Rammaert, A Abry, J C Allo, S Andre, C Andreotti, N Baarir, M Bendahou, L Benlafia, J Bernard, A Berthoumieu, M E Billemont, J Bokobza, A L Brun, E Burggraff, P Canavaggio, M F Carette, E Casalino, S Castro, C Choquet, H Clément, L Colosi, A Dabreteau, S Damelincourt, S Dautheville, M P Debray, M Delay, S Delerme, L Depierre, F Djamouri, F Dumas, M R S Fadel, A Feydey, Y Freund, L Garcia, H Goulet, P Hausfater, E Ilic-Habensus, M O Josse, J Kansao, Y Kieffer, F Lecomte, K Lemkarane, P Madonna, O Meyniard, L Mzabi, D Pariente, J Pernet, F Perruche, J M Piquet, R Ranerison, P Ray, F Renai, E Rouff, D Saget, K Saïdi, G Sauvin, E Trabattoni, N Trimech, C Auger, B Pasquet, S Tamazirt, J M Treluyer, F Tubach, J Wang

Abstract

Introduction: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan.

Methods: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data.

Results: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases.

Conclusions: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP.

Trial registration: ClinicalTrials.gov registry NCT01574066 (February 7, 2012).

Figures

Fig. 1
Fig. 1
Flow chart of the studied population according to the day 28 adjudication committee classification CAP community-acquired pneumonia, CRP C-reactive protein, PCT procalcitonin
Fig. 2
Fig. 2
C-reactive protein (CRP) (upper panel) and procalcitonin (PCT) (lower panel) boxplot for patients according to each level of community-acquired pneumonia diagnosis certainty classification. PCT values greater than 5 μg/L are not shown
Fig. 3
Fig. 3
C-reactive protein ROC curves predicting definite community-acquired pneumonia diagnosis. AUC = 0.787. 95 % CI = 0.717 to 0.857. Youden’s index = 0.501 for an optimal CRP cut-off point at 45.9 mg/L ROC receiver operating characteristic, AUC area under the curve, CI confidence interval, CRP C-reactive protein
Fig. 4
Fig. 4
Procalcitonin ROC curve predicting definite community-acquired pneumonia diagnosis. AUC = 0.655. 95 % CI = 0.570 to 0.739. Youden’s index = 0.307 for an optimal PCT cut-off point at 0.13 μg/L ROC receiver operative characteristic, AUC area under the curve, CI confidence interval, PCT procalcitonin

References

    1. Mandell LA. Epidemiology and etiology of community-acquired pneumonia. Infect Dis Clin North Am. 2004;18:761–76. doi: 10.1016/j.idc.2004.08.003.
    1. Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004;164:637–44. doi: 10.1001/archinte.164.6.637.
    1. Wunderink RG, Waterer GW. Community-acquired pneumonia. N Engl J Med. 2014;370:1863.
    1. Gennis P, Gallagher J, Falvo C, Baker S, Than W. Clinical criteria for the detection of pneumonia in adults: guidelines for ordering chest roentgenograms in the emergency department. J Emerg Med. 1989;7:263–8. doi: 10.1016/0736-4679(89)90358-2.
    1. Metlay JP, Fine MJ. Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med. 2003;138:109–18. doi: 10.7326/0003-4819-138-2-200301210-00012.
    1. Dorca J, Torres A. Lower respiratory tract infections in the community: towards a more rational approach. Eur Respir J. 1996;9:1588–9. doi: 10.1183/09031936.96.09081588.
    1. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014;371:1619–28. doi: 10.1056/NEJMra1312885.
    1. Albaum MN, Hill LC, Murphy M, Li YH, Fuhrman CR, Britton CA, et al. Interobserver reliability of the chest radiograph in community-acquired pneumonia. PORT Investigators. Chest. 1996;110:343–50. doi: 10.1378/chest.110.2.343.
    1. Hopstaken RM, Witbraad T, van Engelshoven JMA, Dinant GJ. Inter-observer variation in the interpretation of chest radiographs for pneumonia in community-acquired lower respiratory tract infections. Clin Radiol. 2004;59:743–52. doi: 10.1016/j.crad.2004.01.011.
    1. Young M, Marrie TJ. Interobserver variability in the interpretation of chest roentgenograms of patients with possible pneumonia. Arch Intern Med. 1994;154:2729–32. doi: 10.1001/archinte.1994.00420230122014.
    1. Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, et al. Early chest CT-scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med. 2015. [Epub ahead of print].
    1. Das D, Le Floch H, Houhou N, Epelboin L, Hausfater P, Khalil A, et al. Viruses detected by systematic multiplex polymerase chain reaction in adults with suspected community-acquired pneumonia attending emergency departments in France. Clin Microbiol Infect. 2015;21:608. doi: 10.1016/j.cmi.2015.02.014.
    1. Ortqvist A, Hedlund J, Wretlind B, Carlström A, Kalin M. Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia. Scand J Infect Dis. 1995;27:457–62. doi: 10.3109/00365549509047046.
    1. Van der Meer V, Neven AK, van den Broek PJ, Assendelft WJ. Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review. BMJ. 2005;331:26. doi: 10.1136/bmj.38483.478183.EB.
    1. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363:600–7. doi: 10.1016/S0140-6736(04)15591-8.
    1. Van Vugt SF, Broekhuizen BD, Lammens C, Zuithoff NP, de Jong PA, Coenen S, et al. Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study. BMJ. 2013;346:f2450. doi: 10.1136/bmj.f2450.
    1. Holm A, Pedersen SS, Nexoe J, Obel N, Nielsen LP, Koldkjaer O, et al. Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care. Br J Gen Pract. 2007;57:555–60.
    1. Niederman MS. Biological markers to determine eligibility in trials for community-acquired pneumonia: a focus on procalcitonin. Clin Infect Dis. 2008;47:S127–32. doi: 10.1086/591393.
    1. Chalmers JD, Singanayagam A, Akram AR, Mandal P, Short PM, Choudhury G, et al. Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis. Thorax. 2010;65:878–83. doi: 10.1136/thx.2009.133280.
    1. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302:1059–66. doi: 10.1001/jama.2009.1297.
    1. Metlay JP, Schulz R, Li YH, Singer DE, Marrie TJ, Coley CM, et al. Influence of age on symptoms at presentation in patients with community-acquired pneumonia. Arch Intern Med. 1997;157:1453–9. doi: 10.1001/archinte.1997.00440340089009.
    1. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50. doi: 10.1056/NEJM199701233360402.
    1. Liu YF, Gao Y, Chen MF, Cao B, Yang XH, Wei L. Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China. BMC Infect Dis. 2013;13:309. doi: 10.1186/1471-2334-13-309.
    1. Noorani HZ, Adams E, Pitrak D, Belinson S, Aronson N. Future research needs on procalcitonin-guided antibiotic therapy: identification of future research needs from comparative effectiveness review No. 78 [Internet] Rockville: Agency for Healthcare Research and Quality (US); 2013.
    1. Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection. 2000;28:68–73. doi: 10.1007/s150100050049.
    1. Müller B, Harbarth S, Stolz D, Bingisser R, Mueller C, Leuppi J, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10. doi: 10.1186/1471-2334-7-10.
    1. Rothberg MB, Pekow PS, Lahti M, Brody O, Skiest DJ, Lindenauer PK. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. 2010;303:2035–42. doi: 10.1001/jama.2010.672.
    1. Justo D, Lachmi S, Saar N, Joffe E, Atzmony L, Mashav N, et al. C-reactive protein velocity following antibiotics in patients with chronic obstructive pulmonary disease exacerbation and community acquired pneumonia. Eur J Intern Med. 2009;20:518–21. doi: 10.1016/j.ejim.2009.03.008.
    1. Albrich WC, Müller B, Harbarth S. Antibiotic therapy in patients hospitalized with acute chronic obstructive pulmonary disease. JAMA. 2010;304:1326. doi: 10.1001/jama.2010.1339.
    1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415–27. doi: 10.1056/NEJMoa1500245.

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