Clinical Progress Note: Procalcitonin in the Management of Pediatric Lower Respiratory Tract Infection

Procalcitonin (PCT) is a biomarker that has shown promise to identify bacterial etiology in acute infections, including bacterial lower respiratory tract infection (LRTI). In 2017, the United States Food and Drug Administration (FDA) approved the use of PCT as a diagnostic aid to guide the decisions around antibiotic therapy in acute LRTI.¹ Although most of the data supporting the use of PCT for LRTI stems from adult studies, the high disease burden, predominance of viral etiologies, and frequent diagnostic uncertainty resulting in antibiotic overuse make pediatric LRTI an ideal target for the use of PCT as a diagnostic aid. This review evaluates and summarizes the current evidence regarding the role of PCT in the clinical care of pediatric LRTI, including its use in guiding antibiotic use and prognosticating disease severity.

The commonly used PCT cut points for withholding or stopping antibiotics in adults and children are 0.1 µg/L (very low risk of bacterial etiology) or 0.25 µg/L (low risk of bacterial etiology).^2-4 Among the 532 children enrolled in the multicenter study of Etiology of Pneumonia in the Community (EPIC), a PCT threshold of 0.25 µg/L demonstrated an approximate sensitivity of 85%, specificity of 45%, positive likelihood ratio of 1.55, and negative likelihood ratio of 0.33 for community acquired pneumonia (CAP) caused by typical bacterial pathogens.⁵ Lowering the cutoff to <0.1 µg/L increased PCT sensitivity to 100%, decreased specificity, positive likelihood ratio, and negative likelihood ratio to 20%, 1.26, and 0, respectively. Although the EPIC study obtained culture and performed PCR testing on any blood sample, pleural fluid specimen, endotracheal aspirate, or bronchoalveolar–lavage specimens obtained during the study period, currently available laboratory methods show poor sensitivity for defining bacterial LRTI. Thus, bacterial etiologies may have been underestimated. The highly negative predictive value demonstrated in this study highlights the potential of PCT as a biomarker for ruling out bacterial diseases, including LRTI.

Multiple studies have evaluated the potential utility of PCT in guiding antibiotic initiation in adults with LRTI, but data on pediatric patients are sparse.⁴ In a randomized, single-center Italian study comparing a PCT-guided algorithm (withholding antibiotics when PCT < 0.25 µg/L) versus usual care among 319 hospitalized children with pneumonia, the PCT group experienced fewer antibiotic initiations (15.5% vs 100%, P < .05) without significant differences in recurrence of respiratory symptoms or new antibiotic prescriptions in the month following enrollment.²

A similar randomized trial using a PCT-guided algorithm for the initiation of antibiotics conducted among 337 Swiss children presented to the emergency department (ED) with pneumonia and other LRTIs failed to demonstrate decreases in antibiotic initiation.³ This study used an algorithm that categorized the likelihood of requiring antibiotic treatment for bacterial LRTI as “definitely” if PCT was >0.5 µg/L, “probably” if PCT was 0.26–0.5 µg/L, “probably not” if PCT was 0.1–0.25 µg/L, and “definitely not” if PCT was <0.1 µg/L. In the PCT group, 104 out of 168 (62%) patients received antibiotics within 14 days compared with 93 out of 165 (56%) patients in the control group (odds ratio [OR]: 1.26, 95% CI: 0.81, 1.95). In the subgroup analyses, the odds of administering antibiotics to those with nonpneumonia LRTI was significantly higher than those of the PCT group and control group (OR: 4.09, 95% CI: 1.8, 9.93); the odds of receiving antibiotics also showed no difference in the subgroup of children with pneumonia (OR: 0.66, 95% CI: 0.35, 1.23).

The benefit of PCT for informing decisions around the initiation of antibiotics likely varies based on perceived risk of bacterial diseases. When the pretest probability of bacterial disease is extremely high, the use of PCT is unlikely to alter treatment decisions. Similarly, PCT should not be used in situations where the pretest probability for bacterial pneumonia is very low—in these instances, an elevated PCT may lead to unnecessary antibiotic use among children presenting to the ED. However, the risk of bacterial pneumonia is often equivocal, and in these situations, PCT may provide clinicians with useful insights, primarily for ruling out bacterial disease.