Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: A randomized controlled trial

Abstract

Objective

The aim of the study was to evaluate the impact of procalcitonin (PCT) measurement on antibiotic use in children with fever without source.

Method

Children aged 1 to 36 months presenting to a pediatric emergency department (ED) with fever and no identified source of infection were eligible to be included in a randomized controlled trial. Patients were randomly assigned to 1 of 2 groups as follows: PCT+ (result revealed to the attending physician) and PCT− (result not revealed). Patients from both groups also had complete blood count, blood culture, urine analysis, and culture performed. Chest radiography or lumbar puncture could be performed if required.

Results

Of the 384 children enrolled and equally randomized into the PCT+ and PCT− groups, 62 (16%) were diagnosed with a serious bacterial infection (urinary tract infection, pneumonia, occult bacteremia, or bacterial meningitis) by primary ED investigation. Ten were also found to be neutropenic (<500 × 10⁶/L). Of the remaining undiagnosed patients, 14 (9%) of 158 received antibiotics in the PCT+ group vs 16 (10%) of 154 in the PCT− group (Δ −2%; 95% confidence interval [CI], −8 to 5). A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have resulted in an increase in antibiotic use by 24% (95% CI, 15-33).

Conclusion

Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source. However, a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have resulted in an increase use of antibiotics.

Introduction

Fever is one of the most frequent reasons for consultation in pediatric emergency departments (EDs). Twenty percent of febrile children younger than 3 years have no localizing sign of infection [1]. Most of these children will have a benign viral infection [2]. Because a well-appearing child does not rule out urinary tract infection (UTI), pneumonia, occult bacteremia, or meningitis, the decision to treat empirically with antibiotics is often based on the results of complementary laboratory tests [2].

Abnormal urine and cerebrospinal fluid (CSF) analysis are used as surrogate markers of positive culture for UTI and meningitis, respectively. For pneumonia, clinicians traditionally treat patients with lobar consolidation on the chest radiography. For a presumptive diagnosis of occult bacteremia, clinicians, in the past, have relied on the complete blood count (CBC) including the absolute neutrophil count despite it has a poor diagnostic accuracy [3], [4], [5], [6], [7], [8], [9], [10], [11]. Because of that, other surrogate markers, such as C-reactive protein (CRP) and procalcitonin (PCT) have been proposed.

Procalcitonin is a calcitonin precursor and is released from all tissues in response to a bacterial infection. Compared to the CRP, the increase in circulating PCT upon bacterial infection or sepsis, is reported to be more rapid and more specific [12]. Almost 10 years ago, Gendrel et al [9] demonstrated the superiority of PCT over CRP in distinguishing a bacterial from a viral infection in children in the ED. This initial observation has since been confirmed with sensitivities and specificities ranging between 73% and 96% and 50% and 94%, respectively, depending upon the study; values are much better than that of white blood cell count (WBC) [5], [7], [8], [9], [10], [11], [13].

Although PCT seems, so far, to be the best surrogate marker for bacterial infection available to clinicians, its real impact on the management of children with fever without source has, to our knowledge, never been evaluated. Thus, the objectives of this study were (1) to evaluate the impact of PCT measurement on antibiotic prescription and on hospitalization rate in children presenting with a fever without source and (2) to evaluate PCT accuracy in detecting bacterial infection as identified through traditional methods in a pediatric ED. Our hypothesis was that PCT would lower antibiotic prescription and hospitalization rate.