1. Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Procalcitonin Use to Predict Bacterial Infection in Febrile Infants Milcent K, Faesch S, Gras-Le Guen C, et al. Use of procalcitonin assays to predict serious bacterial infection in young febrile infants. JAMA Pediatr. Published online November 23, 2015. doi:10.1001/jamapediatrics.2015.3210.

2. Copyright restrictions may apply Background –The procalcitonin (PCT) assay is an accurate screening test for identifying invasive bacterial infection (IBI). However, its value in the evaluation of serious bacterial infection (SBI) and IBI in febrile infants younger than 3 months is not clearly defined. Study Objective –To assess the diagnostic accuracy of the PCT assay for detecting SBIs and IBIs in febrile infants aged 7 to 91 days and to compare its performances with C-reactive protein (CRP), white blood cell (WBC) count, and absolute neutrophil cell (ANC) count, for the overall population and for subgroups of infants according to their age (7-30 or >30 days) and the duration of fever (≤6 hours). Introduction

3. Copyright restrictions may apply Study Design –Prospective multicenter cohort study. Setting –Fifteen French pediatric emergency departments (PEDs) for a period of 30 months. Patients –2047 infants older than 7 days and younger than 91 days with temperature ≥38°C at home or on admission at the PED, without antibiotic treatment within the previous 48 hours, and without major comorbidities. –A list of eligible patients not included was established, and a systematic search for SBI in these patients was conducted. –Parental written informed consent was obtained. Methods

4. Copyright restrictions may apply Methods Outcomes –SBI was defined as the isolation of a bacterial pathogen from the culture of blood, cerebrospinal fluid, urine, or stool samples, including bacteremia and bacterial meningitis classified as IBI. –The diagnostic characteristics of PCT, CRP, WBC count, and ANC count for detecting SBI and IBI were described and compared. –Laboratory test cutoff values were calculated based on receiver operating characteristic (ROC) analysis. Limitations –Blood culture and lumbar puncture were only obtained in 61.5% and 64.8% of included infants, respectively. Patients without blood culture were excluded from the analysis. –Urine culture was not always performed in cases of negative dipstick result. We considered that those patients are unlikely to have urinary tract infections. –The optimal PCT threshold was calculated in isolation and may be different in the multivariate model.

5. Copyright restrictions may apply Results Among the 2047 infants included, 6.8% were diagnosed as having an SBI and 1.0% as having an IBI (11.0% and 1.7% of those with blood culture [n = 1258], respectively). The area under the ROC curve for the detection of IBI for the PCT assay was significantly higher than that for CRP: 0.91 (95% CI, 0.83-0.99) vs 0.77 (95% CI, 0.65-0.89), respectively (P =.002). The PCT assay offered a similar area under the ROC curve than CRP for the detection of SBI: 0.81 (95% CI, 0.75-0.86) vs 0.80 (95% CI, 0.75-0.85), respectively (P =.70). Similar results were obtained for the subgroup of infants aged <1 month and for those with fever <6 hours. For cutoff values of 0.3 ng/mL for PCT and 20 mg/L for CRP, negative likelihood ratios were both 0.3 (95% CI, 0.2-0.5) for identifying SBI and 0.1 (95% CI, 0.03-0.4) and 0.3 (95% CI, 0.2-0.7) for identifying IBI, respectively.

6. Copyright restrictions may apply Results Area Under the Curve (AUC) for the ROC Curves for Biomarkers to Detect Definite SBIs and IBIs

7. Copyright restrictions may apply Results ROC Curves for Biomarkers to Detect Definite SBIs and IBIs Among Infants With Fever Duration <6 Hours

8. Copyright restrictions may apply ROC Curves for Biomarkers to Detect Definite SBIs and IBIs Among Infants Aged 7-30 Days Results

9. Copyright restrictions may apply Results Clinical and Laboratory Predictors of Patients With Bacterial Infections a

10. Copyright restrictions may apply Comment The PCT assay has better test characteristics compared with CRP, ANC count, and WBC count for diagnosing IBIs in febrile infants aged 7 to 91 days admitted to PEDs. The PCT assay has similar diagnostic properties as CRP for detecting SBI in this same population. However, rapid urinalyses are reliable to rule out SBI, contrary to IBI, considering that the most common bacterial infection in this age group is urinary tract infection.

11. Copyright restrictions may apply Comment The PCT assay, using a cutoff value of 0.3 ng/mL, is the best predictor for identifying IBI in young febrile infants. Results suggest that it may be possible: –To improve clinical practice for the management of febrile infants younger than 3 months. –To avoid lumbar puncture, particularly in patients with a PCT level less than 0.3 ng/mL. –To develop decision-making rules incorporating PCT (their effectiveness, cost, and the associated iatrogenic morbidity should be analyzed and the approaches should be validated).

12. Copyright restrictions may apply If you have questions, please contact the corresponding author: –Karen Milcent, MD, MSc, Department of Pediatrics, Hôpital Antoine Béclère, 157 rue de la porte de Triveaux 92140 Clamart, France (karen.milcent@abc.aphp.fr). Funding/Support This work was supported by grants PHRC AOR 06/047 and 10/079 from the French Health Ministry. Conflict of Interest Disclosures None reported. Contact Information