Blood culture indications in critically ill neonates: a multicenter prospective cohort study.

Due to potential lethality of healthcare-associated sepsis (HAS), a low threshold for blood culturing and antimicrobial therapy (ABT) initiation is accepted. We assessed variability in the trigger for blood culturing between three neonatal intensive care units. A multicenter prospective cohort study was conducted. In newborns with suspicion of HAS, 10 predefined clinical signs, nosocomial sepsis (NOSEP) score, C-reactive protein, ABT initiation, and risk factors were registered at time of culturing. Outcome was lab-confirmed HAS, defined according to the NeoKISS-criteria. Two hundred ninety-nine suspected HAS episodes were considered in 212 infants, of which 118 had birth-weight ≤ 1500 g; proportion of lab-confirmed HAS per suspected episode was 30/192 (center 1), 28/60 (center 2), and 8/47 (center 3) (p < 0.001). Median C-reactive protein and number of clinical signs at time of culturing differed between centers 1, 2, and 3 (respectively 11 vs. 5 vs. 3 mg/L, p = 0.001; 1 sign [IQR 0-2, center 1] vs. 3 signs [IQR 2-4, centers 2 and 3], p < 0.001). Median NOSEP score at time of culturing was 5 (IQR 3-8, center 1), 5 (IQR 3-9, center 2), and 8 (IQR 5-11, center 3) (p = 0.016). Difference in ABT initiation was noticed (82 vs. 93 vs. 74%, p = 0.05). CONCLUSION: Center heterogeneity in sampling practice is substantial. Optimizing sampling practice can be recommended. What is Known: • Blood culture test is a common diagnostic procedure in critically-ill newborns. • A low threshold for sampling and antimicrobial therapy initiation is accepted. What is New: • Variability in blood culture practice was assessed between 3 neonatal intensive care units by the registration of sampling frequencies, clinical indications, and antimicrobial therapy initiation.

Impact of healthcare-associated sepsis on mortality in critically ill infants.

UNLABELLED: Healthcare-associated sepsis (HAS) is a life-threatening complication in neonatal intensive care. Research into the impact of HAS on mortality adjusted for comorbidities is however limited. We conducted a historical cohort study to evaluate impact of HAS on mortality stratified by birth weight and risk factors for mortality in the HAS cohort. HAS was defined according to the National Institute of Child Health and Human Development criteria. Logistic regression was used to calculate adjusted odds of mortality. Of 5134 admissions, 342 infants developed HAS (6.7 %). Mortality in the total and HAS cohort was 5.6 and 10.5 %, respectively. The majority of HAS was caused by commensals (HAS-COM, 59.4 %) and 40.6 % by recognized pathogens (HAS-REC). Adjusted for comorbidities, "HAS-REC" is only a risk factor for mortality in newborns >1500 g (adjusted odds ratio [aOR] 2.3, confidence interval [CI] 1.1-4.9). Post-hoc analysis identified HAS-REC as an independent risk factor for mortality in infants with gastrointestinal disease (aOR 4.8, CI 2.1-10.8). "Renal insufficiency," "focal intestinal perforation," and "necrotizing enterocolitis" are independent risk factors for mortality in the HAS cohort (aOR 13.5, CI 4.9-36.6; aOR 7.7, CI 1.5-39.2; aOR 2.1, CI 1.0-4.7, respectively). CONCLUSION: For very low birth weight infants (≤1500 g), several comorbidities overrule the impact of HAS on mortality. After adjustment for comorbidities, HAS-REC independently predicts in-hospital mortality in heavier infants and in those with gastrointestinal disease. WHAT IS KNOWN: • The relationship between healthcare-associated sepsis and mortality is influenced by the causative pathogen and is confounded by comorbidities. • Research on impact of healthcare-associated sepsis on mortality adjusted for comorbidities is limited as well as research on independent risk factors for mortality in neonates with sepsis. What is New: • We included a large list of comorbidities and stratified risk by birth weight in order to assess the true effect of healthcare-associated sepsis on mortality. • Risk for mortality was calculated for commensal flora and for recognized pathogens as causative micro-organisms.

Prediction models for neonatal health care-associated sepsis: a meta-analysis.

BACKGROUND AND OBJECTIVES: Blood culture is the gold standard to diagnose bloodstream infection but is usually time-consuming. Prediction models aim to facilitate early preliminary diagnosis and treatment. We systematically reviewed prediction models for health care-associated bloodstream infection (HABSI) in neonates, identified superior models, and pooled clinical predictors. DATA SOURCES: LibHub, PubMed, and Web of Science. METHODS: The studies included designed prediction models for laboratory-confirmed HABSI or sepsis. The target population was a consecutive series of neonates with suspicion of sepsis hospitalized for ≥ 48 hours. Clinical predictors had to be recorded at time of or before culturing. Methodologic quality of the studies was assessed. Data extracted included population characteristics, total suspected and laboratory-confirmed episodes and definition, clinical parameter definitions and odds ratios, and diagnostic accuracy parameters. RESULTS: The systematic search revealed 9 articles with 12 prediction models representing 1295 suspected and 434 laboratory-confirmed sepsis episodes. Models exhibit moderate-good methodologic quality, large pretest probability range, and insufficient diagnostic accuracy. Random effects meta-analysis showed that lethargy, pallor/mottling, total parenteral nutrition, lipid infusion, and postnatal corticosteroids were predictive for HABSI. Post hoc analysis with low-gestational-age neonates demonstrated that apnea/bradycardia, lethargy, pallor/mottling, and poor peripheral perfusion were predictive for HABSI. Limitations include clinical and statistical heterogeneity. CONCLUSIONS: Prediction models should be considered as guidance rather than an absolute indicator because they all have limited diagnostic accuracy. Lethargy and pallor and/or mottling for all neonates as well as apnea and/or bradycardia and poor peripheral perfusion for very low birth weight neonates are the most powerful clinical signs. However, the clinical context of the neonate should always be considered.

Risk Factors for Health Care-Associated Sepsis in Critically Ill Neonates Stratified by Birth Weight.

BACKGROUND: Health care-associated bloodstream infection (HABSI) is a frequent complication in neonatal intensive care. Research on risk factors stratified by birth weight and adjusted for severity of illness and comorbidities is limited. Our objective is to describe independent risk factors for HABSI in critically ill neonates with emphasis on risk variation between birth weight groups. METHODS: We performed a single-center historical cohort study in a tertiary referral center. A neonatal intensive care-audit system was used to identify eligible neonates admitted for ≥72 hours (2002-2011). HABSI is defined according to National Institute of Child Health and Human Development criteria. Risk factors for HABSI were assessed by univariate and logistic regression analysis for the total cohort and for birth weight subgroups, that is, neonates ≤1500 g and >1500 g. RESULTS: A total of 342 neonates developed HABSI in 5134 admissions of ≥72 hours (6.7%). Very low birth weight, total parenteral nutrition (TPN), mechanical ventilation, gastrointestinal disease, surgery (cardiac and other type), and renal insufficiency are independent risk factors for the total cohort. Gastrointestinal disease and cardiac surgery are independent risk factors in both birth weight groups; mechanical ventilation (odds ratio [OR]: 2.6; confidence interval [CI]: 1.6-4.0) and other type of surgery (OR: 4.3; CI: 2.1-8.8) are solely independent risk factors in the ≤1500-g cohort; TPN is exclusively an independent risk factor (OR: 7.9; CI: 3.9-16.2) in the >1500-g cohort. CONCLUSIONS: In our neonatal intensive care unit, risk stratification by birth weight revealed some difference. Special attention concerning infection control practices is for neonates receiving TPN, mechanical ventilation, cardiac surgery, and with a gastrointestinal disease.