This study was part of a retrospective multicenter study assessing the accuracy of PCT compared with WBC and CRP in diagnosing SBI, more specifically IBI, in well-appearing infants under 3 months of age with FWS presenting to the pediatric emergency department. We refer to the previous article by our research group for a detailed description of the study methods.
Study Setting and Selection of Participants
The study was conducted in 5 Spanish and 2 Italian pediatric emergency departments. The protocols for the management of infants less than 3 months of age with FWS in these pediatric emergency departments are very similar: urine dipstick testing, measurement of CRP, PCT levels and complete blood count, as well as blood and urine cultures are recommended in all patients. A lumbar puncture is individually recommended, according to the age of the infant, the general appearance and the laboratory test results.
Infants younger than 3 months of age presenting with FWS to the pediatric emergency department, who had PCT, CRP, urine dipstick as well as blood culture performed at the time of evaluation were included in the study. Patients were retrospectively included from December 31, 2010 backward, up to a maximum of 3 years earlier (January 1, 2008), depending on when PCT was introduced in each hospital. Regardless of the date of PCT introduction, the study period for each hospital was required to be a multiple of 12 months, to avoid possible epidemiologic variations throughout the year.
Patients were excluded from the study if meeting any of the following criteria:
Patients classified as not well-appearing upon arrival to the pediatric emergency department; patients initially classified as well-appearing but whose clinical situation subsequently worsened were included.
Patients in whom presence of fever was not certain, that is, patients who were afebrile in the pediatric emergency department and whose body temperature was not measured at home with a thermometer. Patients who were afebrile in the pediatric emergency department, but in whom fever was measured at home were included.
PCT was measured using a quantitative immunochemiluminescence assay according to the instructions of the manufacturer (Roche Diagnostics, Mannheim, Germany).
The following data were recorded for included patients at each center: age, sex, month when care was provided, medical history, time elapsed between fever onset (first detection at home) and evaluation in the pediatric emergency department, temperature registered at home and in the pediatric emergency department, child appearance upon arrival, results of any tests performed and final diagnosis.
The following additional data were also provided:
Total number of patients admitted during the study period.
Number of well-appearing infants younger than 3 months of age with FWS admitted during the study period.
Number of infants excluded and the reasons.
FWS was defined as axillary or rectal temperature at home, or rectal temperature in the pediatric emergency department >=38°C, without catarrhal or other respiratory signs/symptoms (such as tachypnea) or a diarrheal process, in patients who had a normal physical examination.
Well-appearing was defined by a normal Pediatric Assessment Triangle in those centers in which this data were systematically recorded in the pediatric medical records. For the other centers, infants were considered to be not well-appearing if the physical examination recorded in the patient medical chart indicated any clinical suspicion of sepsis. The exclusion expressions included, but were not limited to: "poor/bad general appearance," "irritable," "cyanosis," "hypotonic" and "cutis marmorata." SBI was defined as isolation of a bacterial pathogen from the blood, cerebrospinal fluid (CSF), urine or stools.
Infants with a urine culture yielding mixed growth or growth of <50,000 cfu/mL of a single bacterial species and a negative urine dipstick were considered as possible cases of urinary tract infections (UTIs). These patients were classified as possible SBI and analyzed in the non-SBI group. Urine samples for culture were collected by bladder catheterization or suprapubic aspiration in the Spanish centers and in the 2 hospitals in Italy mainly through the use of sterile collection bags changed every 30 minutes, as per local protocol. When bags were used, 2 different positive samples with a concordant bacterial growth >100,000 cfu/mL were required for a definitive diagnosis of UTI.
IBI was defined as isolation of a bacterial pathogen from the blood or CSF. Positive blood and CSF cultures were defined as culture leading to the isolation of bacteria characterized as true pathogens including Streptococcus pneumoniae, Neisseria meningitidis, Enterococcus spp., group A and group B Streptococcus, Staphylococcus aureus and Salmonella spp. Growth of Staphylococcus epidermidis, Propionibacterium acnes, Streptococcus viridans and Diphtheroids from previously healthy immunocompetent infants (with no history of heart disease, ventriculoperitoneal shunts, indwelling catheters or other prosthetic devices) were categorized as contaminants.
The Lab-score, originally derived and validated by Galetto-Lacour et al in 2008, takes into account only predictive variables independently associated with SBI, namely PCT, CRP and urine dipstick. The relative weight of each variable was based on the odds ratio in univariate analysis in the original study. According to the Lab-score, 2 points were attributed to PCT >=0.5 ng/mL or CRP >=40 mg/L, 4 points to PCT >=2 ng/mL or CRP >=100 mg/L and 1 point to positive urine dipstick (ie, positive leukocyte esterase and/or positive nitrate). Consequently, Lab-score values ranged from 0 to 9 points, as reported in Table, Supplemental Digital Content 1, https://links.lww.com/INF/B282. In previous studies, a cutoff point >=3 was identified as the best Lab-score value for SBI prediction in both the derivation and validation sets,[13,14] with a sensitivity ranging from 86% to 94% and a specificity from 78% to 83%.
All data were entered in a Microsoft Office Database by the research coordinator at each center and then reviewed by the principal investigators. Normally distributed data were expressed as mean ± standard deviation; nonnormally distributed data were expressed as median and interquartile range; categoric variables were reported as percentages. For nonnormally distributed data, comparison was performed using Mann–Whitney U test; comparison of normally distributed data was performed using independent-samples t test. For categoric data, the χ2 test was used. Parameters displaying P < 0.05 were considered statistically significant.
The diagnostic performance of the Lab-score and the other laboratory variables considered were compared using a receiver operating characteristic analysis. Sensitivity, specificity, positive and negative predictive values and likelihood ratios (LRs) for different Lab-score cutoff points were calculated. The statistical software programs used were MedCalc Version 11.1 (MedCalc Software, Mariakerke, Belgium) and OpenEpi Version 2.3.1 https://www.OpenEpi.com. The study was approved by the Ethical Committee of the Spanish coordinator center (Cruces Hospital in Bilbao, according to Spanish legislation) and by the 2 independent review boards of the participating Italian centers, that is, Padua and Treviso hospitals, with waiver of informed consent.
Pediatr Infect Dis J. 2012;31(12):1239-1244. © 2012 Lippincott Williams & Wilkins