How to predict serious bacterial infections in young febrile infants in the emergency department?
Journal
Pediatrics and Neonatology
Journal Volume
60
Journal Issue
2
Pages
117-118
Date Issued
2019
Author(s)
Abstract
Fever is the most common reason for young infants (age 90% more than 20 years ago. Nevertheless, due to today's changing epidemiology, the performance of these criteria requires reevaluation. In 2018, Aronson et al. conducted a retrospective case-control study to evaluate the Rochester criteria and the modified Philadelphia criteria for the risk stratification of febrile infants with IBIs aged ≤60 days. They reported that the sensitivity of the modified Philadelphia criteria was higher than that of the Rochester criteria, but the specificity was lower. In addition, two infants with meningitis were misclassified to the Rochester low-risk group without CSF testing when discharged from the ED.3Aronson P.L. Wang M.E. Shapiro E.D. Shah S.S. DePorre A.G. McCulloh R.J. et al.Risk stratification of febrile infants ≤60 Days old without routine lumbar puncture.Pediatrics. 2018; 142 (pii: e20181879)Crossref PubMed Scopus (18) Google Scholar In 2017, Nigrovic et al. demonstrated that neither the YOS score nor the unstructured clinician suspicion reliably identified infants with IBIs aged ≤60 days in a large prospective cohort study.4Nigrovic L.E. Mahajan P.V. Blumberg S.M. Browne L.R. Linakis J.G. Ruddy R.M. et al.The Yale observation Scale score and the risk of serious bacterial infections in febrile infants.Pediatrics. 2017; 140 (pii: e20170695)Crossref Scopus (40) Google Scholar Although these criteria have earlier shown acceptable negative predictive value, there is a need for more accurate clinical and laboratory predictors to risk-stratify febrile infants. When young febrile infants are brought to the ED, the complete blood cell count (CBC) is the most commonly obtained test. However, several studies have demonstrated suboptimal performance characteristics of CBC parameters, including the peripheral white blood cell count, the absolute neutrophil count, and the neutrophil-to-lymphocyte ratio, for IBIs. Nonetheless, these results require further validation. In 2017, Cruz et al. conducted a large prospective observational cohort study and found that CBC parameters had poor accuracy in distinguishing febrile infants with IBIs.5Cruz A.T. Mahajan P. Bonsu B.K. Bennett J.E. Levine D.A. Alpern E.R. et al.Accuracy of complete blood cell counts to identify febrile infants 60 Days or younger with invasive bacterial infections.JAMA Pediatr. 2017; 171e172927Crossref PubMed Scopus (51) Google Scholar The possible explanation for the poor performance of CBC may be the changing epidemiology of IBIs in young infants due to the effect of immunity resulting from the use of conjugate vaccines of Haemophilus influenzae type b and Streptococcus pneumoniae and the development of screening and antibiotic prophylaxis of Group B Streptococcus. The most common pathogens of SBIs identified in the modern era is E. coli; it may produce less of an inflammatory response and less leukocytosis by the host and thus decrease the sensitivity of CBC. Therefore, better diagnostic tools other than the CBC are required in the post-conjugate vaccine era. C-reactive protein (CRP) is the most investigated and a commonly used biomarker. In this issue of Pediatrics and Neonatology, Chiu et al. have reported the findings of their retrospective study conducted at a tertiary medical center in southern Taiwan to evaluate the clinical characteristics and routine blood tests in young febrile infants. They have demonstrated that CRP levels >25 mg/L can predict IBIs with greater accuracy in febrile infants.6Chiu I.M. Huang L.C. Chen I.L. Tang K.S. Huang Y.H. Diagnostic values of C-reactive protein and complete blood cell to identify invasive bacterial infection in young febrile infants.Pediatr Neonatol. 2019; 60: 197-200Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Furthermore, a similar result was reported by Hamiel et al., in 2017, showing that CRP was the best single discriminatory marker of SBIs in young febrile infants compared with CBC. When the CRP level is high (>46.1 mg/L), there is a high risk of developing an SBI.7Hamiel U. Bahat H. Kozer E. Hamiel Y. Ziv-Baran T. Goldman M. Diagnostic markers of acute infections in infants aged 1 week to 3 months: a retrospective cohort study.BMJ Open. 2018; 8e018092Crossref Scopus (15) Google Scholar However, we must pay attention to some factors that may decline the sensitivity of CRP, such as low birth weight or extremely preterm infants and those with an earlier onset of sepsis.8Lai M.Y. Tsai M.H. Lee C.W. Chiang M.C. Lien R. Fu R.H. et al.Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L).BMC Infect Dis. 2015; 15: 320Crossref PubMed Scopus (30) Google Scholar To summarize the above mentioned findings, plasma CRP level could be a good marker for predicting SBIs but not to rule out the early onset of sepsis or guide the empirical choice of antibiotics. Procalcitonin (PCT) has been frequently reported to have higher sensitivity than CRP for the identification of IBIs, although some studies have shown that the accuracy of PCT and CRP was similar for SBIs.9Milcent K. Faesch S. Gras-Le Guen C. Dubos F. Poulalhon C. Badier I. et al.Use of procalcitonin assays to predict serious bacterial infection in young febrile infants.JAMA Pediatr. 2016; 170: 62-69Crossref PubMed Scopus (123) Google Scholar However, a meta-analysis of studies assessing the correlation of PCT cutoff value for the identification of low- and high risk groups among young febrile infants concluded that measuring serum PCT concentrations alone was inferior to the Rochester criteria, although it could distinguish some SBIs.10England J.T. Del Vecchio M.T. Aronoff S.C. Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients.J Emerg Med. 2014; 47: 682-688Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar In addition, PCT might not currently be a routine laboratory investigation in some clinical settings, and it requires a relatively higher cost than that for other biomarkers. Therefore, these limitations restrict the routine usage of PCT for the discrimination of SBIs in young febrile infants in the ED. Other biomarkers for identifying SBIs are currently under investigation, e.g., presepsin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), interleukin-27 (IL-27), soluble urokinase plasminogen activator receptor (suPAR), neutrophil CD64, cell-free DNA, and microRNA. These are considered to be potential markers for sepsis among pediatric patients in the future; however, none of these have yet been applied to clinical use. In conclusion, discriminating infants with SBIs from young febrile infants still remains a disturbing problem for clinicians. None of the clinical criteria or diagnostic markers could be used alone to reduce the risk of making significant errors. PCT and CRP appear to be superior in predicting SBIs compared with CBC, and the clinical criteria have an acceptable negative predictive value for SBIs. However, there is no obvious increasing effect even when these approaches are combined. Therefore, we should still be cautious in case of young febrile infants, and there remains a need to develop better diagnostic methods. The author has no conflicts of interest relevant to this article.
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Publisher
Elsevier (Singapore) Pte Ltd
Type
editorial