Predictors of serious bacterial infections using serum biomarkers in an infant population aged 0 to 90 days: a prospective cohort study

Objective Young febrile infants represent a vulnerable population at risk for serious bacterial infections (SBI). We aimed to evaluate the diagnostic accuracy of components of the complete blood count in comparison with C-reactive protein (CRP) to predict SBI among febrile infants. Design and setting Prospective cohort study conducted in a tertiary emergency department between December 2018 and November 2019. Patients We included febrile infants ≤3 months old with complete blood count results. We analysed their white blood cell count (WBC), absolute neutrophil ratio (ANC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet count ratio, and compared these to the performance of CRP. Main outcome measures SBIs were defined as urinary tract infection, bacteraemia, bacterial meningitis, sepsis, pneumonia, skin and soft tissue infection, bacterial enteritis, septic arthritis or osteomyelitis. Results Of the 187 infants analysed, 54 (28.9%) were diagnosed with SBI. Median values of WBC, ANC, NLR and CRP were significantly higher in infants with SBI: WBC (13.8 vs 11.4×109/L, p=0.004), ANC (6.7 vs 4.1×109/L, p<0.001), NLR (1.3 vs 0.9, p=0.001) and CRP (21.0 vs 2.3 mg/L, p<0.001), compared with those without. CRP had the best discriminatory values for SBI, with area under the curve (AUC) of 0.815 (95% CI 0.747 to 0.883), compared with WBC, ANC and NLR. A predictive model consisting of WBC, ANC and NLR in combination with clinical parameters, had an AUC of 0.814 (95% CI 0.746 to 0.883). There was increased discriminative performance when this predictive model was combined with CRP, (AUC of 0.844, 95% CI 0.782 to 0.906). Conclusion In young febrile infants, CRP was the best discriminatory biomarker for SBI. WBC, ANC and NLR when used in combination have potential diagnostic utility in this population.

[1]  P. Butcher,et al.  PCR for the detection of pathogens in neonatal early onset sepsis , 2020, PloS one.

[2]  Sangsoo Han,et al.  Diagnostic markers of serious bacterial infections in infants aged 29 to 90 days , 2019, Signa Vitae.

[3]  O. Ramilo,et al.  A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections , 2019, JAMA pediatrics.

[4]  Xinmei Huang,et al.  Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity—a retrospective study , 2019, BMJ Open.

[5]  G. Buonocore,et al.  Culture-Negative Early-Onset Neonatal Sepsis — At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship , 2018, Front. Pediatr..

[6]  Samir S. Shah,et al.  Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments , 2018, The Journal of pediatrics.

[7]  D. Djordjević,et al.  Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia? , 2018, Mediators of inflammation.

[8]  S. Sutçuoglu,et al.  Can neutrophil to lymphocyte ratio predict late‐onset sepsis in preterm infants? , 2018, Journal of clinical laboratory analysis.

[9]  E. Kozer,et al.  Diagnostic markers of acute infections in infants aged 1 week to 3 months: a retrospective cohort study , 2018, BMJ Open.

[10]  Ş. Hamilçıkan,et al.  The Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio for Detecting Early-onset Neonatal Sepsis , 2017, Journal of pediatric hematology/oncology.

[11]  O. Ramilo,et al.  Epidemiology of Bacteremia in Febrile Infants Aged 60 Days and Younger , 2017, Annals of emergency medicine.

[12]  M. Hawkes,et al.  The Epidemiology, Management, and Outcomes of Bacterial Meningitis in Infants , 2017, Pediatrics.

[13]  A. Jenkner,et al.  Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis , 2017, BMC Infectious Diseases.

[14]  H. Lee,et al.  Mean Platelet Volume to Platelet Count Ratio as a Promising Predictor of Early Mortality in Severe Sepsis , 2017, Shock.

[15]  T. Greenhow,et al.  Management and Outcomes of Previously Healthy, Full-Term, Febrile Infants Ages 7 to 90 Days , 2016, Pediatrics.

[16]  O. Ramilo,et al.  Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger. , 2016, JAMA.

[17]  A. Rønnestad,et al.  Early-onset Sepsis and Antibiotic Exposure in Term Infants: A Nationwide Population-based Study in Norway , 2015, The Pediatric infectious disease journal.

[18]  Samir S. Shah,et al.  Association of clinical practice guidelines with emergency department management of febrile infants ≤56 days of age. , 2015, Journal of hospital medicine.

[19]  S. Aronoff,et al.  Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients. , 2014, The Journal of emergency medicine.

[20]  P. Nee,et al.  Neutrophil to lymphocyte count ratio as an early indicator of blood stream infection in the emergency department , 2014, Emergency Medicine Journal.

[21]  S. Mintegi,et al.  Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection , 2013, Emergency Medicine Journal.

[22]  G. Demirel,et al.  Inflammatory responses to hepatitis B virus vaccine in healthy term infants , 2013, European Journal of Pediatrics.

[23]  S. Mintegi,et al.  Diagnostic Value of Procalcitonin in Well-Appearing Young Febrile Infants , 2012, Pediatrics.

[24]  Lucy Savitz,et al.  Costs and Infant Outcomes After Implementation of a Care Process Model for Febrile Infants , 2012, Pediatrics.

[25]  B. Resch,et al.  An Update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks , 2012, Neonatology.

[26]  S. Mintegi,et al.  Invasive bacterial infections in a paediatric emergency department in the era of the heptavalent pneumococcal conjugate vaccine , 2012, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[27]  K. Roberts Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months , 2011, Pediatrics.

[28]  T. Berger,et al.  Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial , 2009, Neonatology.

[29]  J. Emparanza,et al.  Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin , 2009, Archives of Disease in Childhood.

[30]  M. Plebani,et al.  Procalcitonin and C-Reactive Protein as Diagnostic Markers of Severe Bacterial Infections in Febrile Infants and Children in the Emergency Department , 2007, The Pediatric infectious disease journal.

[31]  B. Korczowski Procalcitonin and C-reactive protein in vaccination-associated adverse reactions. , 2004, The Pediatric infectious disease journal.

[32]  Mitchell M. Levy,et al.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference , 2003, Intensive Care Medicine.

[33]  Joan M Hengst The role of C-reactive protein in the evaluation and management of infants with suspected sepsis. , 2003, Advances in neonatal care : official journal of the National Association of Neonatal Nurses.

[34]  J. Beyene,et al.  Predicting the outcome of neonatal bacterial meningitis. , 2000, Pediatrics.

[35]  A. Madan,et al.  Serial Serum C-Reactive Protein Levels in the Diagnosis of Neonatal Infection , 1998, Pediatrics.

[36]  D. Korones,et al.  Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. , 1994, Pediatrics.

[37]  M. Charron,et al.  Pyuria and bacteriuria in urine specimens obtained by catheter from young children with fever. , 1994, The Journal of pediatrics.

[38]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[39]  T. van der Poll,et al.  UvA-DARE ( Digital Academic Repository ) Markers of infectious disease emergencies : Focus on patients with community-acquired pneumonia , 2013 .

[40]  R. Záhorec Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. , 2001, Bratislavske lekarske listy.