The Value of Perinatal Factors, Blood Biomarkers and Microbiological Colonization Screening in Predicting Neonatal Sepsis

Background: Neonatal sepsis is one of the most important causes of elevated morbidity and mortality rates in neonatal intensive care units worldwide. While the clinical manifestations of neonatal sepsis tend to be nonspecific, its rapid development and life-threatening potential call for reliable markers for early detection. Methods: We conducted a retrospective single-center study including all neonates suspected of having developed neonatal sepsis from 2013 to 2016. Perinatal and clinical characteristics as well as microbiological and laboratory findings were evaluated. Neonatal sepsis was defined as either culture-proven sepsis (positive blood culture) or clinical sepsis (at least one symptom and elevated C-reactive protein (CRP) concentrations within 72 h with negative blood culture). We further differentiated between early-onset (EOS) and late-onset (LOS) sepsis. Results: Microbiological colonization screening by throat and rectal swabs frequently did not detect the organism that subsequently caused the sepsis. Depending on the age of the newborn with sepsis (EOS or LOS), associations between different anamnestic and clinical factors (prenatal or postnatal ones) were found. In particular, the central–peripheral temperature difference showed a strong association with LOS. Laboratory results useful for the early detection of neonatal sepsis included interleukin-6 (IL-6) and CRP concentrations. Conclusions: Elevated IL-6 >100 ng/L was a strong marker for neonatal sepsis. When choosing the antibiotics for treatment, data from microbiological colonization screening should be considered but not solely relied on. Some indicators of infection also depended on postnatal age.

[1]  J. Lepercq,et al.  Factors associated with a latency < 7 days after preterm premature rupture of membranes between 22 and 32 weeks of gestation in singleton pregnancies. , 2021, Journal of gynecology obstetrics and human reproduction.

[2]  Carlos F. Narváez,et al.  Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis , 2020, American Journal of Perinatology.

[3]  B. Poindexter,et al.  Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies. , 2020, JAMA pediatrics.

[4]  E. Molloy,et al.  Challenges in developing a consensus definition of neonatal sepsis , 2020, Pediatric Research.

[5]  V. Lamba,et al.  Standardizing the approach to late onset sepsis in neonates through antimicrobial stewardship: a quality improvement initiative , 2020, Journal of Perinatology.

[6]  R. Polin,et al.  A Neonatal Sequential Organ Failure Assessment Score Predicts Mortality to Late-Onset Sepsis in Preterm Very Low Birth Weight Infants , 2019, Pediatric Research.

[7]  T. Eckmanns,et al.  Sepsis prediction during outbreaks at neonatal intensive care units through body surface screening for Gram-negative bacteria: systematic review and meta-analysis , 2018, BMC Research Notes.

[8]  T. Eckmanns,et al.  Routine screening for colonization by Gram-negative bacteria in neonates at intensive care units for the prediction of sepsis: systematic review and meta-analysis. , 2018, The Journal of hospital infection.

[9]  T. Nguyen,et al.  Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype , 2016, Critical care medicine.

[10]  Y. Wu,et al.  Interleukin-6 and interleukin-8 in diagnosing neonatal septicemia. , 2016, Journal of biological regulators and homeostatic agents.

[11]  N. Laforgia,et al.  Early and Late Infections in Newborns: Where Do We Stand? A Review. , 2016, Pediatrics and neonatology.

[12]  H. Hoyer,et al.  Intensified colonisation screening according to the recommendations of the German Commission for Hospital Hygiene and Infectious Diseases Prevention (KRINKO): identification and containment of a Serratia marcescens outbreak in the neonatal intensive care unit, Jena, Germany, 2013–2014 , 2016, Infection.

[13]  H. V. Baum,et al.  Mikrobiologisches Screening bei Frühgeborenen , 2016, Monatsschrift Kinderheilkunde.

[14]  J. D. Bard,et al.  Diagnosis of Bloodstream Infections in Children , 2016 .

[15]  R. Bellomo,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[16]  F. Pulzer,et al.  The role of elevated central-peripheral temperature difference in early detection of late-onset sepsis in preterm infants. , 2015, Early human development.

[17]  P. Du,et al.  [Diagnostic value of interleukin 6 for neonatal sepsis: a Meta analysis]. , 2015, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[18]  J. W. Fjalstad Neonatal sepsis and the adverse effect of antibiotic treatment - a systematic review , 2015 .

[19]  R. Lien,et al.  Predictors of clinical and microbiological treatment failure in neonatal bloodstream infections. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[20]  Krinko Praktische Umsetzung sowie krankenhaushygienische und infektionspräventive Konsequenzen des mikrobiellen Kolonisationsscreenings bei intensivmedizinisch behandelten Früh- und Neugeborenen , 2013 .

[21]  R. Black,et al.  Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis , 2013, PLoS medicine.

[22]  D. Körholz,et al.  [Results of surveillance cultures on a neonatal intensive care unit: a retrospective analysis]. , 2013, Zeitschrift fur Geburtshilfe und Neonatologie.

[23]  C. Lindsell,et al.  The pediatric sepsis biomarker risk model , 2012, Critical Care.

[24]  A. Martinez-Gimeno,et al.  Central-peripheral temperature gradient: an early diagnostic sign of late-onset neonatal sepsis in very low birth weight infants , 2012, Journal of perinatal medicine.

[25]  P. Smith,et al.  Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. , 2012, Early human development.

[26]  L. Saiman,et al.  Statewide NICU Central-Line-Associated Bloodstream Infection Rates Decline After Bundles and Checklists , 2011, Pediatrics.

[27]  K. Sarafidis,et al.  Diagnostic utility of elevated serum soluble triggering receptor expressed on myeloid cells (sTREM)-1 in infected neonates , 2010, Intensive Care Medicine.

[28]  P. Lachman,et al.  Using care bundles to prevent infection in neonatal and paediatric ICUs , 2009, Current opinion in infectious diseases.

[29]  P. Tsao,et al.  Neonatal sepsis: a 6-year analysis in a neonatal care unit in Taiwan. , 2009, Pediatrics and neonatology.

[30]  Robert Koch-Institut Empfehlung zur Prävention nosokomialer Infektionen bei neonatologischen Intensivpflegepatienten mit einem Geburtsgewicht unter 1500 g , 2007, Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz.

[31]  N. Curtis,et al.  How Reliable Is a Negative Blood Culture Result? Volume of Blood Submitted for Culture in Routine Practice in a Children's Hospital , 2007, Pediatrics.

[32]  N. Mathers,et al.  Diagnostic audit of C-reactive protein in neonatal infection , 1987, European Journal of Pediatrics.

[33]  K. Maitland,et al.  Bacteremia among children admitted to a rural hospital in Kenya. , 2005, The New England journal of medicine.

[34]  J. Vincent,et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure , 1996, Intensive Care Medicine.

[35]  Mikael Norman,et al.  Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial. , 2004, Pediatrics.

[36]  P. Auld,et al.  Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis. , 2003, American journal of perinatology.

[37]  Vineet Bhandari,et al.  Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile , 2003, Journal of perinatal medicine.

[38]  F. Signore,et al.  C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity, risk status, antenatal and perinatal complications, and infection. , 2003, Clinical chemistry.

[39]  A. Philip,et al.  Use of C-Reactive Protein in Minimizing Antibiotic Exposure: Experience With Infants Initially Admitted to a Well-Baby Nursery , 2000, Pediatrics.

[40]  G. Steinbach,et al.  Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants. , 1999, The Pediatric infectious disease journal.

[41]  G. Lipowsky,et al.  Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation , 1998, The Lancet.

[42]  C. Niemeyer,et al.  Plasma Levels and Gene Expression of Granulocyte Colony-Stimulating Factor, Tumor Necrosis Factor-α, Interleukin (IL)-1β, IL-6, IL-8, and Soluble Intercellular Adhesion Molecule-1 in Neonatal Early Onset Sepsis , 1998, Pediatric Research.

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

[44]  T F Fok,et al.  Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants , 1997, Archives of disease in childhood. Fetal and neonatal edition.

[45]  S. Ehl,et al.  C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection. , 1997, Pediatrics.

[46]  P. Bartmann,et al.  Interleukin-6: A Sensitive Parameter for the Early Diagnosis of Neonatal Bacterial Infection , 1994, Pediatrics.

[47]  H. Bada,et al.  Significance of serial C-reactive protein responses in neonatal infection and other disorders. , 1993, Pediatrics.

[48]  R. Cooke,et al.  Receiver operating characteristic curves for comparison of serial neutrophil band forms and C reactive protein in neonates at risk of infection. , 1992, Archives of disease in childhood.

[49]  A. Meiser,et al.  Interleukin 6 as early mediator in neonatal sepsis. , 1992, The Pediatric infectious disease journal.

[50]  A. Philip,et al.  Early Diagnosis of Neonatal Sepsis , 1980, Pediatrics.

[51]  D. Goldmann,et al.  Evaluation of blood culture procedures in a pediatric hospital , 1979, Journal of clinical microbiology.