Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

GloveCare: a pilot study in preparation for a cluster crossover randomized controlled trial of non-sterile glove-based care in preventing late-onset infection in the NICU.

BACKGROUND: Late-onset infections (LOI) are a major cause of morbidity and mortality among patients in the neonatal intensive care unit (NICU). Gloving after hand hygiene may be a pragmatic approach to prevent infections that arise when healthcare workers' hands transmit pathogens to neonates. OBJECTIVE: To determine the feasibility of conducting a multicenter, open-labeled randomized controlled trial (RCT) to determine whether a protocol that requires healthcare workers (HCWs) in a level 3 NICU to wear non-sterile gloves plus hand hygiene reduces the occurrence of a late-onset infection, compared to hand hygiene alone. METHODS: In this single-center pilot study, we recruited neonates admitted to the McMaster Children's Hospital NICU from June 2017 to May 2018. The NICU was randomized to begin with the standard (control) arm for 6 months (June 2017 to Dec 2017), followed by the gloving (GloveCare) arm for 6 months (Jan 2018 to July 2018), with a 2-week washout period in-between to educate healthcare workers about gloving. We measured numerous feasibility outcomes including enrollment, event rate, and compliance with hand hygiene (Moment 1: before patient contact, Moment 2: before clean procedure, Moment 3: after body fluid contact, Moment 4: after patient contact) and gloving compliance. RESULTS: We enrolled 750 neonates (390 Standard care, 360 GloveCare) and achieved 100% enrollment. We found higher hand hygiene compliance during the standard care arm compared to the GloveCare for all four moments of hand hygiene (Moment 1: 87% vs 79%, OR=1.86 (1.34, 2.59); Moment 2: OR=1.73 (1.00, 3.01); Moment 3: OR=1.11 (0.62, 1.98); Moment 4: OR=1.65 (1.27, 2.14)). We developed and validated a method to calculate glove compliance, which ranged from 48 to 85%, and was highest for moment 3 (doffing after a procedure or body fluid exposure risk). No adverse events were documented for patients or staff. DISCUSSION: Reduction in hand hygiene compliance in the GloveCare arm presents a pragmatic challenge in ascertaining the effectiveness of gloving to prevent LOI. Most LOIs were non-sterile-site infections, which is considered a less patient-important or clinically relevant outcome compared to sterile-site LOI. Ensuring efficient collection and validation of hand hygiene and gloving data is imperative. CONCLUSION: The pilot study demonstrated the feasibility of this intervention though modifications to improve hand hygiene compliance during GloveCare will be important prior to a multicenter cluster RCT to assess the efficacy of non-sterile glove-based care in preventing LOI in the NICU. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03078335.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, Setting, and Participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main Outcomes and Measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and Relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

Machine Learning Used to Compare the Diagnostic Accuracy of Risk Factors, Clinical Signs and Biomarkers and to Develop a New Prediction Model for Neonatal Early-onset Sepsis.

BACKGROUND: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs. STUDY DESIGN: Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier. RESULTS: One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random. CONCLUSIONS: Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.

Cost impact of procalcitonin-guided decision making on duration of antibiotic therapy for suspected early-onset sepsis in neonates.

BACKGROUNDS: The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. METHODS: Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. RESULTS: In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category 'infection unlikely' and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic. CONCLUSIONS: Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category 'infection unlikely,' and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.

Completeness of reporting of quality improvement studies in neonatology is inadequate: a systematic literature survey.

INTRODUCTION: Quality improvement (QI) is a growing field of inquiry in healthcare, but the reporting quality of QI studies in neonatology remains unclear. We conducted a systematic survey of the literature to assess the reporting quality of QI studies and factors associated with reporting quality. METHODS: We searched Medline for publications of QI studies from 2016 to 16 April 2020. Pairs of reviewers independently screened citations and assessed reporting quality using a 31-item modified Standards for Quality Improvement Reporting Excellence, 2nd edition (SQUIRE 2.0) checklist. We reported the number (percentage) of studies that reported each item and their corresponding 95% CIs. We used Poisson regression to explore factors associated with reporting quality, namely, journal endorsement of SQUIRE 2.0, declaration of funding sources, year of publication and number of authors. The results were reported as incidence rate ratio (IRR) and 95% CI. RESULTS: Of 1921 citations, 336 were eligible; among them, we randomly selected 100 articles to assess reporting quality. The mean (standard deviation) number of SQUIRE 2.0 items adhered to was 22.0 (4.5). Percentage of articles reporting each item varied from 26% to 100%. Journal endorsement of SQUIRE 2.0 (IRR=1.11, 95% CI 1.02 to 1.21, p=0.015), declaration of funding sources and increasing number of authors were significantly associated with better reporting. CONCLUSIONS: Reporting quality of QI studies in neonatology is inadequate. Endorsing the SQUIRE 2.0 guideline is a step that journals can implement to enhance the completeness of reporting.

Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.

BACKGROUND & AIMS: In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. METHODS: This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. RESULTS: Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n = 52, control n = 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. CONCLUSIONS: This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.

C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

BACKGROUND: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.

C-reactive protein as a predictor of meningitis in early onset neonatal sepsis: a single unit experience.

Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.

Incidence, risk factors, and outcomes of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

OBJECTIVES: To determine the incidence and risk factors for pulmonary hypertension (PH) in preterm infants with moderate to severe bronchopulmonary dysplasia (BPD) and to compare short-term outcomes. METHODS: Preterm infants <32 weeks gestation born August 2013 through July 2015 with moderate to severe BPD at 36 weeks postmenstrual age were categorized into BPD-PH (exposure) and BPD-noPH (control) groups. RESULTS: Of 92 infants with BPD, 87 had echocardiographic assessment, of whom 24 (28%) had PH. On multiple logistic regression after adjustment for gestational age and sex, no significant risk factors for PH were identified based on data from this cohort. There were no differences in resource utilization or clinical outcomes including survival to discharge. CONCLUSION: Approximately one out of four patients with moderate to severe BPD were identified as having PH. No significant risk factors for PH were identified. No differences in outcomes were identified for those with and without PH.

Fast I(n)dentification of Pathogens in Neonates (FINDPATH-N): protocol for a prospective pilot cohort study of next-generation sequencing for pathogen identification in neonates with suspected sepsis.

INTRODUCTION: Sepsis is a major source of morbidity and mortality in neonates; however, identification of the causative pathogens is challenging. Many neonates have negative blood cultures despite clinical evidence of sepsis. Next-generation sequencing (NGS) is a high-throughput, parallel sequencing technique for DNA. Pathogen-targeted enrichment followed by NGS has the potential to be more sensitive and faster than current gold-standard blood culture. In this pilot study, we will test the feasibility and pathogen detection patterns of pathogen-targeted NGS in neonates with suspected sepsis. Additionally, the distribution and diagnostic accuracy of biomarkers cell-free DNA and protein C levels at two time points will be explored. METHODS AND ANALYSIS: We will conduct a prospective, pilot observational study. Neonates over 1 kg with suspected sepsis from a single tertiary care children's hospital will be recruited for the study. Recruitment will be censored at 200 events or 6 months' duration. Two blood study samples will be taken: the first simultaneous to the blood culture (time=0 hour, for NGS and biomarkers) via an exception to consent (deferred consent) and another 24 hours later after prospective consent (biomarkers only). Neonates will be adjudicated into those with clinical sepsis, culture-proven sepsis and without sepsis based on clinical criteria. Feasibility parameters (eg, recruitment) and NGS process time will be reported.For analysis, NGS results will be described in aggregate, compared with the simultaneous blood culture (sensitivity and specificity) and reviewed via expert panel for plausibility. Pilot data for biomarker distribution and diagnostic accuracy (sensitivity and specificity) for distinguishing between septic and non-septic neonates will be reported. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Hamilton Integrated Research Ethics Board. We will seek publication of study results in peer-reviewed journals.

Childhood and adolescent mental health of NICU graduates: an observational study.

OBJECTIVE: To investigate the mental health of children and adolescents admitted to neonatal intensive/special care units (NICUs) in infancy. METHODS: This cross-sectional study used a provincially representative cohort from the 2014 Ontario Child Health Study. Parents provided data on psychiatric disorders using the MINI International Neuropsychiatric Interview for Children and Adolescents in 3141 children aged 4-11 years (NICU n=389; control n=2752) and in 2379 children aged 12-17 years (NICU n=298; control n=2081). Additionally, 2235 adolescents aged 12-17 years completed the interview themselves (NICU n=285; control n=1950). Odds of psychiatric disorder were compared in those admitted and controls. RESULTS: Based on parent reports, NICU graduates aged 4-11 years had increased adjusted ORs (95% CI) of 1.78 (1.39 to 2.28) for any psychiatric disorder, with a marginal prevalence of 32.4% in NICU participants and 27.6% in controls. At this age, NICU graduates also had increased ORs of 1.74 (1.25 to 2.40) for psychiatric comorbidity, 1.48 (1.04 to 2.11) for oppositional defiant disorder, 1.61 (1.19 to 2.19) for attention-deficit hyperactivity disorder, 4.11 (2.33 to 7.25) for separation anxiety disorder and 2.13 (1.37 to 3.31) for specific phobia. At 12-17 years, 40.5% and 30.5% of NICU graduates and 30.6% and 17.9% of controls had any psychiatric disorder as reported by parents and self-report, respectively. Parents and adolescents, respectively, reported increased adjusted ORs (95% CI) of 1.63 (1.18 to 2.26) and 1.55 (1.13 to 2.11) for any disorder, 1.64 (1.06 to 2.54) and 1.74 (1.11 to 2.73) for psychiatric comorbidity, and 1.89 (1.22 to 2.93) and 3.17 (2.03 to 4.95) for oppositional defiant disorder. CONCLUSIONS: NICU graduates are at increased risk for psychiatric disorders during childhood and adolescence.

Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns).

BACKGROUND: Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. METHODS: We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. FINDINGS: Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI -4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (-5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group). INTERPRETATION: Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death. FUNDING: The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.

Video recording of neonatal resuscitation: A feasibility study to inform widespread adoption.

AIM: To determine the feasibility of introducing video recording (VR) of neonatal resuscitation (NR) in a perinatal centre. METHODS: This was a prospective cohort quality improvement study on preterm infants and their caregivers. Based on evidence and experience of other centers using VR intervention, a contextually relevant implementation and evaluation strategy was designed in the planning phase. The components of intervention were pre-resuscitation team huddle, VR of NR and video debriefing (VD), all occurring on the same day. Various domains of feasibility and sustainability as well as feasibility criteria were predefined. Data for analysis was collected using quantitative and qualitative methods. RESULTS: Seventy-one caregivers participated in VD of 14 NRs facilitated by six trained instructors. Ninety-one percent of caregivers perceived enhanced learning and patient safety and, 48 issues were identified related to policy, caregiver roles, and latent safety threats. Ninety percent of caregivers expressed their willingness to participate in VD activity and supported the idea of integrating it into a resuscitation team routine. Eighty-three percent and 50% of instructors expressed satisfaction with video review software and quality of audio VR. No issues about maintenance of infant or caregivers' confidentiality and erasure of videos were reported. Criteria for feasibility were met (refusal rate of < 10%, VR performed on > 50% of occasions, and < 20% caregivers' perceiving a negative impact on team performance). Necessary adaptations to enhance sustainability were identified. CONCLUSION: VR of NR as a standard of care quality assurance activity to enhance caregivers' learning and create opportunities that improve patient safety is feasible. Despite its complexity with inherent challenges in implementation, the intervention was acceptable, implementable, and potentially sustainable with adaptations.

Introduction of microsystems in a level 3 neonatal intensive care unit-an interprofessional approach.

BACKGROUND: Growth of neonatal intensive care units in number and size has raised questions towards ability to maintain continuity and quality of care. Structural organization of intensive care units is known as a key element for maintaining the quality of care of these fragile patients. The reconstruction of megaunits of intensive care to smaller care units within a single operational service might help with provision of safe and effective care. METHODS/DESIGN: The clinical team and patient distribution lay out, admission and discharge criteria and interdisciplinary round model was reorganized to follow the microstructure philosophy. A working group met weekly to formulate the implementation planning, to review the adaptation and adjustment process and to ascertain the quality of implementation following the initiation of the microsystem model. DISCUSSION: In depth examination of microsystem model of care in this study, provides systematic evaluation of this model on variable aspects of health care. The individual projects of this trial can be source of solid evidence for guidance of future decisions on optimized model of care for the critically ill newborns. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02912780 . Retrospectively registered on 22 September 2016.

Use of high noninvasive respiratory support pressures in preterm neonates: a single-center experience.

PURPOSE: To describe the incidence, indications and clinical outcomes following high pressures on noninvasive respiratory support (NRS) in preterm neonates. STUDY DESIGN: Retrospective cohort study of all neonates with BW <1.500 g admitted from July 2012 to June 2014 and placed on high noninvasive respiratory support (NRS), defined as mean airway pressure ≥10 cm H2O for at least 12 continuous hours using nasal continuous positive airway pressure (NCPAP) and/or nasal high-frequency ventilation (NIHFV). Clinical and physiological outcomes following high NRS were ascertained. Median (IQR) and percentages were used to describe continuous and categorical data, respectively. RESULTS: There were 131 instances of high NRS use in 70 of 315 eligible infants. Most common indication was post-extubation, observed in 37% (49/131) of high NRS instances. Intubation was avoided in 71% (93/131) of instances in the first 7 days following high NRS initiation. There were no physiological perturbations in heart rate, blood pressure or oxygen requirement. Furthermore, there were no instances of lung hyperinflation, pneumothoraces or spontaneous intestinal perforation following high NRS. CONCLUSION: The use of high NRS pressure was followed by avoidance of intubation in the majority of cases without adverse effects. Further research on high NRS use including its indications, clinical outcomes and safety profile is warranted.

Variation in Current Management of Term and Late-preterm Neonates at Risk for Early-onset Sepsis: An International Survey and Review of Guidelines.

BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

Self-disinfecting sink drains reduce the Pseudomonas aeruginosa bioburden in a neonatal intensive care unit.

AIM: Water in sink drains is a known source of gram-negative bacteria. We aimed to evaluate the impact of self-disinfecting sink drains on the emission of aerosolised bacteria and on Pseudomonas aeruginosa acquisition among neonates. METHODS: Aerosol bacterial growth and patient Pseudomonas aeruginosa acquisition rates were measured at baseline (Phase One), for 13 months after sinks were relocated or redesigned during refurbishment (Phase Two) and for 13 months after introducing self-disinfecting sink drains (Phase Three). RESULTS: Cultures were positive for bacterial growth in 56%, 24% and 13% of the tested aerosols in Phases One, Two and Three, respectively. Comparing Phases Two and Three produced an odds ratio (OR) of 0.47, with a 95% confidence interval (CI) of 0.22-0.99 (p = 0.047), for all bacteria and an OR of 0.31 and CI of 0.12-0.79 (p = 0.013) for Pseudomonas aeruginosa. Rates of Pseudomonas aeruginosa positive clinical cultures were 0.34, 0.27 and 0.13 per 1000 patient days during the respective phases, with a significant increase of time to the next positive clinical culture in Phase Three. CONCLUSION: Self-disinfecting sink drains were superior to sink replacements in preventing emissions from aerosols pathogens and may reduce hospital-acquired infections. The bioburden reduction should be confirmed in a larger multicentre trial.

Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial.

BACKGROUND: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success. OBJECTIVE: To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis. METHODS: This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children's Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age >or=34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48-72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values. RESULTS: 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics >or=72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12-0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events. CONCLUSION: Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.