Community-Acquired Pneumonia: Evaluation and Diagnosis
Biologic Markers
Two biologic markers—procalcitonin and C-reactive protein (CRP)—can be used in conjunction with history, physical examination, laboratory tests, and imaging studies to assist in the diagnosis and treatment of CAP.24 Procalcitonin is a peptide precursor of the hormone calcitonin that is released by parenchymal cells into the bloodstream, resulting in increased serum level in patients with bacterial infections. In contrast, there is no remarkable procalcitonin level increase with viral or noninfectious inflammation. The reference value of procalcitonin in the blood of an adult individual without infection or inflammation is < 0.15 ng/mL. In the blood, procalcitonin has a half-life of 25 to 30 hours. The quantitative immunoluminometric method (LUMI test, Brahms PCT, Berlin, Germany) is the preferred test to use because of its high sensitivity.33 A meta-analysis of 12 studies involving more than 2400 patients with CAP demonstrated that serum procalcitonin does not have sufficient sensitivity or specificity to distinguish between bacterial and nonbacterial pneumonia. The authors concluded that procalcitonin level cannot be used to decide whether an antibiotic should be administered.34
A 2012 Cochrane meta-analysis that involved 4221 patients with acute respiratory infections (with half of the patients diagnosed with CAP) from 14 prospective trials found the use of procalcitonin test for antibiotic use significantly decreased median antibiotic exposure from 8 to 4 days without an increase in treatment failure, mortality rates in any clinical setting (eg, outpatient clinic, emergency room), or length of hospitalization.35 An update of the 2012 Cochrane review that examined the safety and efficacy of using procalcitonin for starting or stopping antibiotics again demonstrated procalcitonin use was associated with a reduction of antibiotic use (2.4 days).36 A prospective study conducted in France on 100 ICU patients showed that increased procalcitonin from day 1 to day 3 has a poor prognosis factor for severe CAP, whereas decreasing procalcitonin levels is associated with a favorable outcome.37
Because of conflicting data, the 2019 ATS/IDSA guidelines do not recommend using procalcitonin to determine need for initial antibacterial therapy.26
CRP is an acute phase protein produced by the liver. CRP level in the blood increases in response to acute infection or inflammation. Use of CRP in assisting diagnosis and guiding treatment of CAP is more limited in part due to its poor specificity. A prospective study conducted on 168 consecutive patients who presented with cough showed that a CRP level > 40 mg/L had a sensitivity and specificity of 70% and 90%, respectively.38
Summary
CAP remains a leading cause of hospitalization and death in the 21st century. Traditionally, pneumococcus has been considered the major pathogen causing CAP; however, the 2015 EPIC study found that S. pneumoniae was detected in only 5% of patients diagnosed with CAP. Despite the new findings, it is still recommended that empiric treatment for CAP target common typical bacteria (pneumococcus, H. influenzae, Moraxella catarrhalis) and atypical bacteria (M. pneumonia, C. pneumoniae, L. pneumophila).
Because diagnosing pneumonia through history and clinical examination is less than 50% sensitive, a chest imaging study (a plain chest radiograph or a chest CT scan) is usually required to make the diagnosis. Laboratory tests, such as sputum Gram stain/culture, blood culture, urinary antigen tests, PCR test, procalcitonin, and CRP are important adjunctive diagnostic modalities to assist in the diagnosis and management of CAP. However, because no single test is sensitive and specific enough to be a stand-alone test, they should be used in conjunction with history, physical examination, and imaging studies.