Download PDF
Semin Respir Crit Care Med 2024; 45(02): 200-206
DOI: 10.1055/s-0043-1777771
Review Article

Biomarkers: Are They Useful in Severe Community-Acquired Pneumonia?

Pedro Póvoa
1   NOVA Medical School, Centre for Integrated Research in Health, New University of Lisbon, Lisbon, Portugal
2   Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Centre for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
3   Department of Intensive Care, São Francisco Xavier Hospital, CHLO, Lisbon, Portugal
,
Melissa Pitrowsky
4   Postgraduate Program of Internal Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil
,
Gonçalo Guerreiro
3   Department of Intensive Care, São Francisco Xavier Hospital, CHLO, Lisbon, Portugal
,
Mariana B. Pacheco
5   Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
6   D'Or Institute for Research and Education, Rio de Janeiro, Brazil
,
Jorge I.F. Salluh
4   Postgraduate Program of Internal Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil
6   D'Or Institute for Research and Education, Rio de Janeiro, Brazil
› Author Affiliations Funding J.I.F.S. is supported in part by individual research grants from CNPq and FAPERJ.
› Further Information
    Permissions and Reprints

Abstract

Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.

Keywords

Community-Acquired Pneumonia - Severe community – Acquired Pneumonia - Biomarkers - C-Reactive Protein - Procalcitonin - Intensive Care Unit


Publication History

Article published online:
09 January 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Moniz P, Coelho L, Póvoa P. Antimicrobial stewardship in the intensive care unit: the role of biomarkers, pharmacokinetics, and pharmacodynamics. Adv Ther 2021; 38 (01) 164-179
    Google Scholar
  • 2 Povoa P, Kalil AC. Any role for biomarker-guide algorithms in antibiotic stewardship programs?. Crit Care Med 2020; 48 (05) 775-777
    Google Scholar
  • 3 Nora D, Salluh J, Martin-Loeches I, Póvoa P. Biomarker-guided antibiotic therapy-strengths and limitations. Ann Transl Med 2017; 5 (10) 208-208
    Google Scholar
  • 4 Póvoa P, Coelho L, Bos LDJ. New biomarkers for respiratory infections. Curr Opin Pulm Med 2020; 26 (03) 232-240
    Google Scholar
  • 5 Póvoa P, Coelho L, Dal-Pizzol F. et al. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians. Intensive Care Med 2023; 49 (02) 142-153
    Google Scholar
  • 6 Ebell MH, Bentivegna M, Cai X, Hulme C, Kearney M. Accuracy of biomarkers for the diagnosis of adult community-acquired pneumonia: a meta-analysis. Acad Emerg Med 2020; 27 (03) 195-206
    Google Scholar
  • 7 Cals JWL, Butler CC, Hopstaken RM, Hood K, Dinant GJ. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. BMJ 2009; 338 (01) b1374
    Google Scholar
  • 8 Rachina S, Bobylev A, Lazarev P. et al. Biomarker value in the diagnosis of community-acquired pneumonia with concomitant chronic heart failure. J Clin Med 2021; 10 (19) 4570
    Google Scholar
  • 9 Do NTT, Ta NTD, Tran NTH. et al. Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial. Lancet Glob Health 2016; 4 (09) e633-e641
    Google Scholar
  • 10 Claessens YE, Debray MP, Tubach F. et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med 2015; 192 (08) 974-982
    Google Scholar
  • 11 Méndez R, Menéndez R, Cillóniz C. et al. Initial inflammatory profile in community-acquired pneumonia depends on time since onset of symptoms. Am J Respir Crit Care Med 2018; 198 (03) 370-378
    Google Scholar
  • 12 García Vázquez E, Martínez JA, Mensa J. et al. C-reactive protein levels in community-acquired pneumonia. Eur Respir J 2003; 21 (04) 702-705
    Google Scholar
  • 13 Schuetz P, 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
    Google Scholar
  • 14 Kamat IS, Ramachandran V, Eswaran H, Guffey D, Musher DM. Procalcitonin to distinguish viral from bacterial pneumonia: a systematic review and meta-analysis. Clin Infect Dis 2020; 70 (03) 538-542
    Google Scholar
  • 15 Lawandi A, Oshiro M, Warner S. et al. Reliability of admission procalcitonin testing for capturing bacteremia across the sepsis spectrum: real-world utilization and performance characteristics, 65 U.S. hospitals, 2008–2017. Crit Care Med 2023. Accessed July 28, 2023 at: https://journals.lww.com/10.1097/CCM.0000000000005968
    Google Scholar
  • 16 Self WH, Balk RA, Grijalva CG. et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017; 65 (02) 183-190
    Google Scholar
  • 17 Patel N, Adams C, Brunetti L, Bargoud C, Teichman AL, Choron RL. Evaluation of procalcitonin's utility to predict concomitant bacterial pneumonia in critically ill COVID-19 patients. J Intensive Care Med 2022; 37 (11) 1486-1492
    Google Scholar
  • 18 Hessels LM, Speksnijder E, Paternotte N. et al; COVIDPredict Study Group. Procalcitonin-guided antibiotic prescription in patients with COVID-19: a multicenter observational cohort study. Chest 2023; 164 (03) 596-605
    Google Scholar
  • 19 Galli F, Bindo F, Motos A. et al; CIBERESUCICOVID Project investigators (COV20/00110, ISCIII). Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients. Intensive Care Med 2023; 49 (08) 934-945
    Google Scholar
  • 20 Wang Y, Zhang S, Li L, Xie J. The usefulness of serum procalcitonin, C-reactive protein, soluble triggering receptor expressed on myeloid cells 1 and Clinical Pulmonary Infection Score for evaluation of severity and prognosis of community-acquired pneumonia in elderly patients. Arch Gerontol Geriatr 2019; 80: 53-57
    Google Scholar
  • 21 Zhou H, Guo S, Lan T, Ma S, Zhang F, Zhao Z. Risk stratification and prediction value of procalcitonin and clinical severity scores for community-acquired pneumonia in ED. Am J Emerg Med 2018; 36 (12) 2155-2160
    Google Scholar
  • 22 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 (02) 349-355
    Google Scholar
  • 23 Huang DT, Weissfeld LA, Kellum JA. et al; GenIMS Investigators. Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia. Ann Emerg Med 2008; 52 (01) 48-58.e2
    Google Scholar
  • 24 Rabello LSCF, Pitrowsky MT, Soares M, Póvoa P, Salluh JIF. Novos marcadores biológicos na pneumonia comunitária grave. Rev Bras Ter Intensiva 2011; 23 (04) 499-506
    Google Scholar
  • 25 Liu D, Xie L, Zhao H, Liu X, Cao J. Prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with community-acquired pneumonia: a systematic review and meta-analysis. BMC Infect Dis 2016; 16 (01) 232
    Google Scholar
  • 26 Song S, Jia Q, Chen X. et al. Serum suPAR associated with disease severity and mortality in elderly patients with community-acquired pneumonia. Scand J Clin Lab Invest 2020; 80 (06) 515-522
    Google Scholar
  • 27 Arulkumaran N, Khpal M, Tam K, Baheerathan A, Corredor C, Singer M. Effect of antibiotic discontinuation strategies on mortality and infectious complications in critically ill septic patients: a meta-analysis and trial sequential analysis. Crit Care Med 2020; 48 (05) 757-764
    Google Scholar
  • 28 Póvoa P, Coelho L, Bos LJ. Biomarkers in pulmonary infections. Clin Pulm Med 2019; 26 (04) 118-125
    Google Scholar
  • 29 Jensen JU, Hein L, Lundgren B. et al; Procalcitonin And Survival Study (PASS) Group. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011; 39 (09) 2048-2058
    Google Scholar
  • 30 Oliveira CF, Botoni FA, Oliveira CRA. et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med 2013; 41 (10) 2336-2343
    Google Scholar
  • 31 Póvoa P, Coelho L, Almeida E. et al. C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study. Eur Respir J 2005; 25 (05) 804-812
    Google Scholar
  • 32 Borges I, Carneiro R, Bergo R. et al; NIIMI – Núcleo Interdisciplinar de Investigação em Medicina Intensiva. Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers. Crit Care 2020; 24 (01) 281
    Google Scholar
  • 33 Martin-Loeches I, Torres A, Nagavci B. et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Eur Respir J 2023; 61 (04) 2200735
    Google Scholar
  • 34 Cuquemelle E, Soulis F, Villers D. et al; A/H1N1 REVA-SRLF Study Group. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med 2011; 37 (05) 796-800
    Google Scholar
  • 35 Bello S, Mincholé E, Fandos S. et al. Inflammatory response in mixed viral-bacterial community-acquired pneumonia. BMC Pulm Med 2014; 14 (01) 123
    Google Scholar
  • 36 Dolci A, Robbiano C, Aloisio E. et al. Searching for a role of procalcitonin determination in COVID-19: a study on a selected cohort of hospitalized patients. Clin Chem Lab Med 2020; 59 (02) 433-440
    Google Scholar
  • 37 Tsalik EL, Henao R, Montgomery JL. et al; Antibacterial Resistance Leadership Group. Discriminating bacterial and viral infection using a rapid host gene expression test. Crit Care Med 2021; 49 (10) 1651-1663
    Google Scholar