Three factors for successful interpretation of PCR in community-acquired pneumonia in children: specimen selection, cycle threshold, and biomarkers

Introduction. Community-acquired pneumonia (CAP) maintains a leading position in the morbidity and mortality structure of the pediatric population. The introduction of polymerase chain reaction (PCR) methods has expanded diagnostic capabilities; however, it has also brought to the forefront issues regarding the choice of respiratory specimen and the interpretation of results, considering cycle threshold (Ct) values and asymptomatic colonization.

Objective. To systematize current data on the diagnostic value of various respiratory specimens in PCR diagnostics of CAP in children, to define the applicability limits of cycle thresholds for differentiating infection from colonization, and to justify the necessity of integrating molecular methods with biomarkers.

Methods. A systematic literature search was conducted in the PubMed, Scopus, Web of Science, Google Scholar, Cochrane Library and eLibrary databases (2000–2026). A total of 83 studies were selected for the final analysis.

Results. Three key factors for the successful interpretation of PCR diagnostics were identified: specimen selection, Ct interpretation, and integration with biomarkers. It is shown that the diagnostic value of nasopharyngeal (NP) swabs for verifying pneumococcal etiology of CAP approaches zero due to the high frequency of colonization (40–60%), making sterile loci the only reliable source. In contrast, for Mycoplasma pneumoniae, oropharyngeal swabs are optimal (sensitivity 96.2%), while saliva demonstrates comparable results. Critically important for the Russian Federation is the identification of 36–41% macrolide-resistant M. pneumoniae strains with regional variations; 62% of cases are accompanied by viral coinfection (parainfluenza 28%, SARS-CoV-2 19%, RSV 12%). A Ct value < 25 in Mycoplasma infection serves as an independent predictor of severe disease and necessitates hospitalization. For respiratory syncytial virus (RSV), Ct < 25 is associated with severe disease (adjusted odds ratio, aOR 2.26); for human metapneumovirus (hMPV), Ct < 27 (aOR 4.32). Procalcitonin-guided protocols can reduce inappropriate antibiotic prescriptions; however, the heterogeneity of pediatric data dictates the need for multi-marker approaches, including heparin-binding protein (HBP), with sensitivity 82%, specificity 86%, and its combination with procalcitonin increasing the area under the curve (AUC) to 0.94.

Conclusion. The success of PCR diagnostics for CAP in children is determined by three factors: appropriate specimen selection, correct interpretation of Ct values, and integration with biomarkers.

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