Introduction
Pneumonia infects and causes inflammation of the air sacs in one or both lungs. As a result, the air sacs of the infected person are filled with fluid or pus. This leads to health complications, including cough with phlegm, fever, chills, and difficulty in breathing. The causative agent for Pneumonia can be bacteria, viruses, or fungi. Lower Respiratory Tract Infection (LRTI) is a synonym for Pneumonia. People with Pneumonia have the following symptoms:
- Pain in the chest during breathing and coughing
- Difficulty in breathing
- Fatigue
- Cough with phlegm
- Persistent fever, sweating, and chills
- Lower body temperature
- Confusion and mental problems in the older population.
- Nausea and vomiting
Newborns may or may not show signs of the infection. Adults above 65 years, children below two years with symptoms of Pneumonia, and people taking immunosuppressants have a high-risk factor of getting Pneumonia. Community-acquired Pneumonia, Hospital- Acquired Pneumonia, Ventilator-associated pneumonia, and Aspiration Pneumonia are the classifications for Pneumonia.
Now, to treat conditions like Pneumonia, it is necessary to know the higher or lower presence of infection in the lungs with the proper diagnosis. In addition, knowledge about the higher or lower level of infection in the lungs helps prescribe the right amount of antibiotics and other medications. Thus, biomarkers for infection play an essential role. For example, a biomarker can be a molecule or a structure or a process that influences or predicts the incidence of a disease. In addition, they effectively monitor the patient’s response to infection by speculating on the disease severity and treatment response.
An ideal diagnostic biomarker for infection shows the following properties:
- The biomarker level is low or absent when an infection is absent and high when an infection is present.
- It yields faster results than conventional test results.
- It has high specificity or sensitivity and helps characterize severity and monitor treatment response even without clinical signs.
Thus, here comes Procalcitonin as a diagnostic biomarker for Pneumonia. Procalcitonin is the precursor or prohormone of Calcitonin (CT), constituting 116 amino acids. It is produced by the Parafollicular (C-cells) of the thyroid gland and neuroendocrine cells of the lungs & intestine. Procalcitonin is coded by the CALC-1 gene located on chromosome 11.
Procalcitonin is one of the valuable biomarkers in identifying bacterial infection because the level of Procalcitonin increases rapidly within two to four hours from the onset of a bacterial infection.
Procalcitonin as a biomarker has different roles in the human body, including:
- Diagnosing the severity of renal failure in urinary tract infection in children.
- Diagnosis and monitor medullary thyroid carcinoma
- Diagnose bacterial infections, stratify risk, and monitor the risk of septic shock.
- Monitoring the response to antibacterial therapy
- Diagnosis of septicemia and bacteremia in neonates, children, and adults.
This article throws light on the role of Procalcitonin as a biomarker for Pneumonia. Also, we have highlighted other novel biomarkers that have shown better results than Procalcitonin.
Why is Procalcitonin a diagnostic biomarker for Pneumonia?
Reducing the overuse of antibiotics for sepsis is a global health priority. Unfortunately, lower respiratory tract infection is not an exception and is among the most common reasons for an antibiotic prescription. However, most antibiotic prescriptions are unnecessary or inappropriate, and sometimes, they exceed the recommended duration. The over period of antibiotics in LRTI patients occurs because of the difficulty distinguishing between viral and bacterial infections. The difficulty in determining arises because of the similarity in the signs and symptoms of bacterial and viral LRTIs. Also, the results from the microbiological tests take time. Also, most of the time, the pathogen cannot be identified.
Thus, in patients with lower respiratory tract infections, procalcitonin can be a helpful adjunct to clinical judgment for guiding antibiotic therapy and resolving diagnostic uncertainty.
The PROS of using Procalcitonin as a biomarker for Pneumonia include:
- Procalcitonin discriminates better between viral and bacterial infections.
- The results of the Procalcitonin can be obtained in an hour or less.
- Procalcitonin is 65-70% accurate in distinguishing bacterial from the viral pathogen in community-acquired Pneumonia.
- Procalcitonin has been shown to reduce the risk of mortality or morbidity by 25-50% when used as part of an algorithm combined with clinical judgment in patients with LRTIs.
- Procalcitonin helps in guiding antibiotic therapy and thus prevents excessive use of unnecessary antibiotics without causing any adverse effects. In addition, it reduces the risk of antibiotic resistance.
- Procalcitonin is used only to determine when to discontinue antibiotic therapy in patients with known or suspected Ventilator-associated Pneumonia (VAP).
- PCT appears to be the most effective diagnostic marker for pneumococcal Pneumonia in pediatric patients, leading to early beta-lactam therapy.
- Procalcitonin helps determine early antibiotic discontinuation among patients who are critically ill due to Community-acquired Pneumonia. In general, when the procalcitonin level falls below 0.5 ng/mL, antibiotics are stopped.
Most trials evaluating the critically ill use a higher procalcitonin threshold (0.5 ng/mL) than that used for stable patients with respiratory tract infections (0.25 ng/mL), presumably because baseline levels in critically ill patients are expected to be abnormal. Other experts use a lower threshold for antibiotic discontinuation, typically 0.25 ng/mL. The guidelines are based on randomized trials testing procalcitonin in critically sick patients, as well as a body of evidence supporting procalcitonin’s use to guide antibiotic treatment in LRTI patients in general.
The table below shows the interpretation of Procalcitonin Test Results in patients with acute respiratory tract infection:
| PROCALCITONIN LEVEL | SUGGESTED ACTION |
|---|---|
| < 0.1 ng per mL | Antibiotics strongly discouraged |
| 0.1-0.24 ng per mL | Antibiotics discouraged |
| 0.25- 0.50 ng per mL | Antibiotics encouraged |
| >0.50 ng per mL | Antibiotics strongly encouraged |
The drawbacks of Procalcitonin as a biomarker include:
- In addition, PCT is elevated in various non-infectious conditions, such as cirrhosis, pancreatitis, mesenteric infarction, burns, and aspiration pneumonitis.
- The diagnostic and predictive value declines in patients with severe sepsis and localized infections (e.g., endocarditis, empyema).
- Patients with VAP have already developed systemic inflammatory response syndromes, multiple organ failure, and/or previous infection, making PCT less reliable for diagnosis of VAP.
- Although it’s used as a biomarker for pneumococcal Pneumonia in pediatric patients, PCT should be used with caution.
Thus, apart from Procalcitonin, more sensitive and specific novel biomarkers have shown positive results but are still under extensive research for their use as a diagnostic tool for CAP and VAP. These include:
- C-reactive protein
- Interleukin-6
- Complete Blood Count and Platelets
- Neutrophil CD64 receptor
- D-Dimer
- TREM-1 that stands for Triggering Receptor Expressed on Myeloid Cells-1
- Prohormones
- Genome-wide transcriptional studies
- Microbiomics & Proteomics
Christian Mueller et al. carried out a study on patients with acute dyspnea to compare the diagnostic accuracy of procalcitonin, interleukin 6, and CRP to diagnose Pneumonia. The study enrolled 690 patients. The study findings/ results include:
- One hundred seventy-eight patients had an adjudicated final diagnosis of Pneumonia.
- Patients with Pneumonia showed a higher level of Procalcitonin, interleukin 6, and CRP
- Interleukin 6 and CRP showed higher diagnostic accuracy than Procalcitonin.
The study concluded that the clinical utility of procalcitonin was lower than expected.
Similarly, another prospective surveillance study by Wesley H Self et al. had an objective to evaluate the association of serum procalcitonin in CAP. The study was carried out on adult patients hospitalized with community-acquired Pneumonia. The study results found that a higher procalcitonin level strongly correlates with an increased probability of bacterial pathogens.
Published Literature that showed evidence of procalcitonin having a role in guiding treatment of respiratory tract infection
| Sl. No | Title of the Literature | Published Journal | Conclusion |
|---|---|---|---|
| 1 | Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomized, single-blinded intervention trial | The Lancet | Procalcitonin-guided therapy reduced antibiotic use from 83 to 44 percent without changes in quality-of-life scores, laboratory or physiologic parameters, hospital admissions, length of hospitalization, or mortality. |
| 2 | Procalcitonin guidance of antibiotic therapy in community-acquired Pneumonia: a randomized trial | American Journal of Respiratory and Critical Care Medicine | Procalcitonin-guided therapy reduced total antibiotic exposure and the duration of antibiotic use in community-acquired Pneumonia. |
Procalcitonin has a high potential to be a useful biomarker in guiding the initiation of antibiotics therapy for Pneumonia. By looking at the pros and published Literature on procalcitonin, one can analyze that PCT-guided therapy combined with pneumonia treatment guidelines can reduce the use of antibiotics to treat acute respiratory tract infections without compromising patient care.
References
- Karakioulaki, M., & Stolz, D. (2019). Biomarkers in Pneumonia-Beyond Procalcitonin. International journal of molecular sciences, 20(8), 2004. https://doi.org/10.3390/ijms20082004
- Desiree Wussler, Nikola Kozhuharov, Mucio Tavares Oliveira, Aline Bossa, Zaid Sabti, Albina Nowak, Karsten Murray, Jeanne du Fay de Lavallaz, Patrick Badertscher, Raphael Twerenbold, Samyut Shrestha, Dayana Flores, Thomas Nestelberger, Joan Walter, Jasper Boeddinghaus, Tobias Zimmermann, Luca Koechlin, Arnold von Eckardstein, Tobias Breidthardt, Christian Mueller, Alexandre Soeiro, Priscila Goldstein, Tânia Strabelli, Célia Strunz, Karin Wildi, Christian Puelacher, Katharina Rentsch, Assen Goudev, Clinical Utility of Procalcitonin in the Diagnosis of Pneumonia, Clinical Chemistry, Volume 65, Issue 12, 1 December 2019, Pages 1532–1542, https://doi.org/10.1373/clinchem.2019.306787
- Self WH, Balk RA, Grijalva CG, Williams DJ, Zhu Y, Anderson EJ, Waterer GW, Courtney DM, Bramley AM, Trabue C, Fakhran S, Blaschke AJ, Jain S, Edwards KM, Wunderink RG. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis. 2017 Jul 15;65(2):183-190. doi: 10.1093/cid/cix317. PMID: 28407054; PMCID: PMC5850442.
- Procalcitonin use in lower respiratory tract infections. Accessed at
https://www.uptodate.com/contents/procalcitonin-use-in-lower-respiratory-tract-infections#H2786522145 - What is procalcitonin (PCT)? Accessed at
https://www.medscape.com/answers/2096589-179642/what-is-procalcitonin-pct - Pneumonia. Accessed at
https://www.mayoclinic.org/diseases-conditions/pneumonia/diagnosis-treatment/drc-20354210 - Ebell M. Procalcitonin-guided treatment of respiratory tract infections. Am Fam Physician. 2008 Sep 15;78(6):756-7. PMID: 18819243.
- Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Müller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8. PMID: 14987884.
- Creamer, A. W., Kent, A. E., & Albur, M. (2019). Procalcitonin in respiratory disease: use as a biomarker for diagnosis and guiding antibiotic therapy. Breathe (Sheffield, England), 15(4), 296–304. https://doi.org/10.1183/20734735.0258-2019
- Christ-Crain M, Stolz D, Bingisser R, Müller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Müller B. Procalcitonin guidance of antibiotic therapy in community-acquired Pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93. doi: 10.1164/rccm.200512-1922OC. Epub 2006 Apr 7. PMID: 16603606.
