Semin Respir Crit Care Med 2012; 33(03): 266-271
DOI: 10.1055/s-0032-1315638
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biomarkers and Community-Acquired Pneumonia: Tailoring Management with Biological Data

Antoni Torres
1   Department of Pneumology, Clinic Institute of Thorax (ICT), Hospital Clinic of Barcelona- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)- University of Barcelona (UB), Barcelona, Spain.
,
Paula Ramirez
2   Unidad de cuidados Intensivos, Hospital Universitario i Politecnic La Fe, Valencia, Spain.
,
Beatriz Montull
2   Unidad de cuidados Intensivos, Hospital Universitario i Politecnic La Fe, Valencia, Spain.
,
Rosario Menéndez
2   Unidad de cuidados Intensivos, Hospital Universitario i Politecnic La Fe, Valencia, Spain.
› Author Affiliations
Further Information

Publication History

Publication Date:
20 June 2012 (online)

Abstract

Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases worldwide, with an incidence of 0.3 to 0.5% in the adult population. A new diagnostic and prognostic approach relies on evaluation of biomarkers as an expression of the host's inflammatory response against the microorganism. C-reactive protein (CRP), procalcitonin (PCT), and cytokines are the most frequently studied, whereas pro-adrenomedullin (pro-ADM), pro-vasopressin (pro-VNP), and others are currently obtaining promising results. Their usefulness for diagnosis is limited, although PCT has been successfully used to guide prescription of antibiotics in patients with suspected CAP. Nevertheless, the accuracy of PCT in distinguishing between bacterial or viral infection and safely withholding antibiotics in CAP is the subject of debate. Analysis of systemic biomarkers in addition to clinical scores [Pneumonia Severity Index (PSI) or CURB-65 (confusion, urea, respiratory, blood pressure, >65 years)/CRB-65 (confusion, respiratory, blood pressure)] has been shown to improve 30 day mortality prediction and absence of severe complications. Pro-ADM is probably the biomarker that correlates most strongly with mortality prediction. During treatment, ~15% of hospitalized CAP patients develop treatment failure, and almost 6% may manifest rapidly progressive pneumonia. Initially increased and persistent raised levels of biomarkers and cytokines have been shown to identify patients at risk of treatment failure, thereby aiding clinical management. Data from the literature appear to support the use of biomarkers in routine clinical practice to improve the decision making in CAP.

 
  • References

  • 1 Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA 1999; 281 (1) 61-66
  • 2 Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 2002; 165 (6) 766-772
  • 3 Deng JC, Standiford TJ. The systemic response to lung infection. Clin Chest Med 2005; 26 (1) 1-9
  • 4 Müller B, Süess E, Schuetz P , et al. Circulating levels of pro-atrial natriuretic peptide in lower respiratory tract infections. J Intern Med 2006; 260 (6) 568-576
  • 5 Masiá M, Papassotiriou J, Morgenthaler NG, Hernández I, Shum C, Gutiérrez F. Midregional pro-A-type natriuretic peptide and carboxy-terminal provasopressin may predict prognosis in community-acquired pneumonia. Clin Chem 2007; 53 (12) 2193-2201
  • 6 Müller B, Morgenthaler N, Stolz D , et al. Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections. Eur J Clin Invest 2007; 37 (2) 145-152
  • 7 Masiá M, Papassotiriou J, Morgenthaler NG, Hernández I, Shum C, Gutiérrez F. Midregional pro-A-type natriuretic peptide and carboxy-terminal provasopressin may predict prognosis in community-acquired pneumonia. Clin Chem 2007; 53 (12) 2193-2201
  • 8 Bijlsma JJ, Burghout P, Kloosterman TG , et al. Development of genomic array footprinting for identification of conditionally essential genes in Streptococcus pneumoniae. Appl Environ Microbiol 2007; 73 (5) 1514-1524
  • 9 Luna CM. C-reactive protein in pneumonia: let me try again. Chest 2004; 125 (4) 1192-1195
  • 10 Gibot S, Cravoisy A, Levy B , et al. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 2004; 350 (5) 451-458
  • 11 Almirall J, Bolíbar I, Toran P , et al; Community-Acquired Pneumonia Maresme Study Group. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest 2004; 125 (4) 1335-1342
  • 12 Flanders SA, Stein J, Shochat G , et al. Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough. Am J Med 2004; 116 (8) 529-535
  • 13 Müller B, Harbarth S, Stolz D , et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis 2007; 7: 10
  • 14 Polzin A, Pletz M, Erbes R , et al. Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis. Eur Respir J 2003; 21 (6) 939-943
  • 15 Van dM V, Neven AK, Van den Broek PJ , et al. Diagnostic value of C-reactive protein in infections of the lower respiratory tract: systematic review. BMJ 2005; 331: 26
  • 16 Korppi M, Kröger L. C-reactive protein in viral and bacterial respiratory infection in children. Scand J Infect Dis 1993; 25 (2) 207-213
  • 17 Heiskanen-Kosma T, Korppi M. Serum C-reactive protein cannot differentiate bacterial and viral aetiology of community-acquired pneumonia in children in primary healthcare settings. Scand J Infect Dis 2000; 32 (4) 399-402
  • 18 Virkki R, Juven T, Rikalainen H, Svedström E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax 2002; 57 (5) 438-441
  • 19 Prat C, Domínguez J, Rodrigo C , et al. Procalcitonin, C-reactive protein and leukocyte count in children with lower respiratory tract infection. Pediatr Infect Dis J 2003; 22 (11) 963-968
  • 20 Moulin F, Raymond J, Lorrot M , et al. Procalcitonin in children admitted to hospital with community acquired pneumonia. Arch Dis Child 2001; 84 (4) 332-336
  • 21 Toikka P, Irjala K, Juvén T , et al. Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing bacterial and viral pneumonia in children. Pediatr Infect Dis J 2000; 19 (7) 598-602
  • 22 García Vázquez E, Martínez JA, Mensa J , et al. C-reactive protein levels in community-acquired pneumonia. Eur Respir J 2003; 21 (4) 702-705
  • 23 Masiá M, Gutiérrez F, Shum C , et al. Usefulness of procalcitonin levels in community-acquired pneumonia according to the patients outcome research team pneumonia severity index. Chest 2005; 128 (4) 2223-2229
  • 24 Masiá M, Gutiérrez F, Padilla S , et al. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors. Clin Microbiol Infect 2007; 13 (2) 153-161
  • 25 Prat C, Domínguez J, Andreo F , et al. Procalcitonin and neopterin correlation with aetiology and severity of pneumonia. J Infect 2006; 52 (3) 169-177
  • 26 Boussekey N, Leroy O, Georges H, Devos P, d'Escrivan T, Guery B. Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 2005; 33 (4) 257-263
  • 27 Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection 2000; 28 (2) 68-73
  • 28 Krüger S, Ewig S, Papassotiriou J , et al; CAPNETZ Study Group. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: results from the German competence network CAPNETZ. Respir Res 2009; 10: 65
  • 29 Nyamande K, Lalloo UG, John M. TB presenting as community-acquired pneumonia in a setting of high TB incidence and high HIV prevalence. Int J Tuberc Lung Dis 2007; 11 (12) 1308-1313
  • 30 Christ-Crain M, Stolz D, Bingisser R , et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174 (1) 84-93
  • 31 Christ-Crain M, Jaccard-Stolz D, Bingisser R , 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 (9409) 600-607
  • 32 Schuetz PH, Christ-Crain M, Thomann R , et al; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302 (10) 1059-1066
  • 33 Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM. Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia. Clin Microbiol Infect 2002; 8 (2) 93-100
  • 34 Müller F, Christ-Crain M, Bregenzer T , et al; ProHOSP Study Group. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 2010; 138 (1) 121-129
  • 35 Menéndez R, Martínez R, Reyes S , et al. Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia. Thorax 2009; 64 (7) 587-591
  • 36 Krüger S, Ewig S, Marre R , et al; CAPNETZ Study Group. Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes. Eur Respir J 2008; 31 (2) 349-355
  • 37 Menéndez R, Martinez R, Reyes S , et al. Stability in community-acquired pneumonia: one step forward with markers?. Thorax 2009; 64 (11) 987-992
  • 38 Menéndez R, Torres A, Rodríguez de Castro F , et al; Neumofail Group. Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients. Clin Infect Dis 2004; 39 (12) 1783-1790
  • 39 Menéndez R, Cavalcanti M, Reyes S , et al. Markers of treatment failure in hospitalised community acquired pneumonia. Thorax 2008; 63 (5) 447-452
  • 40 Ramírez P, Ferrer M, Martí V , et al. Inflammatory biomarkers and prediction for intensive care unit admission in severe community-acquired pneumonia. Crit Care Med 2011; 39 (10) 2211-2217
  • 41 Krüger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T ; German Competence Network for the Study of Community Acquired Pneumonia (CAPNETZ) Study Group. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med 2010; 182 (11) 1426-1434
  • 42 Guertler C, Wirz B, Christ-Crain M, Zimmerli W, Mueller B, Schuetz P. Inflammatory responses predict long-term mortality risk in community-acquired pneumonia. Eur Respir J 2011; 37 (6) 1439-1446
  • 43 Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Müller B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 2005; 9 (6) R816-R824
  • 44 Christ-Crain M, Morgenthaler NG, Stolz D , et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit Care 2006; 10 (3) R96
  • 45 Albrich WC, Dusemund F, Rüegger K , et al. Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC Infect Dis 2011; 11: 112