Trends in C-Reactive Protein Use in Early-Onset Sepsis Evaluations and Associated Antibiotic Use.

OBJECTIVES: To determine the prevalence of C-reactive protein (CRP) use in early-onset sepsis (EOS) evaluations in neonatal intensive care units (NICUs) across the United States over time and to determine the association between CRP use and antibiotic use. STUDY DESIGN: A retrospective cohort study of NICUs contributing data to Premier Healthcare Database from 2009 through 2021. EOS evaluation was defined as a blood culture charge <3 days after birth. CRP use for each NICU was calculated as the proportion of infants with a CRP test obtained <3 days after birth among those undergoing an EOS evaluation and categorized as, low (<25%); medium-low (25 to <50%), medium-high (50 to <75%), and high (≥75%). Outcomes included antibiotic use and mortality ≤7 days after birth. RESULTS: Among 572 NICUs, CRP use varied widely and was associated with time. The proportion of NICUs with high CRP use decreased from 2009 to 2021 (24.7% vs. 17.4%, P <0.001), and low CRP use NICUs increased (47.9% vs. 64.8%, P <0.001). Compared with low use NICUs, high use NICUs more frequently continued antibiotics >3 days (10% vs. 25%, P<0.001). This association persisted in multivariable-adjusted regression analyses (aRR 1.95, 95%CI 1.54, 2.48). Risk of mortality was not different in high use NICUs (adjusted risk difference -0.02%, 95%CI -0.04%, 0.0008%). CONCLUSIONS: CRP use in EOS evaluations varied widely across NICUs. High CRP use was associated with prolonged antibiotic therapy but not mortality ≤7 days after birth. Reducing routine CRP use in EOS evaluations may be a target for neonatal antibiotic stewardship efforts.

Diagnostic Performance and Patient Outcomes With C-Reactive Protein Use in Early-Onset Sepsis Evaluations.

OBJECTIVES: To determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP. STUDY DESIGN: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units. CRP was used routinely in early-onset sepsis evaluations during 2009-2014; this period was used to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed early-onset sepsis. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014. RESULTS: From 2009 to 2014, 10 134 infants were admitted; 9103 (89.8%) had CRP and 7549 (74.5%) had blood culture obtained within 3 days of birth. CRP obtained ±4 hours from blood culture had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, we observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period. Rate and timing of early-onset sepsis detection, transfer to a greater level of care, and in-hospital mortality were not different between periods. CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in early-onset sepsis. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.

Knowledge, Attitudes, and Perceptions about Antibiotic Stewardship Programs among Neonatology Trainees.

OBJECTIVE: Antibiotic stewardship should be an essential component of neonatology training as neonatal intensive care units (NICU) have unique stewardship needs. Our aim was to assess neonatology fellowship trainees' knowledge, attitudes, and perceptions about antibiotic stewardship to inform sustainable curriculum development. STUDY DESIGN: We distributed an electronic survey to neonatology fellows in the United States over 4 months (January-April 2018) via Accreditation Council for Graduate Medical Education program directors. RESULTS: Of 99 programs in the United States with an estimated 700 fellows, 159 (23%) fellows from 52 training programs (53%) responded to the survey and 139 (87%) provided analyzed responses. Majority of respondents were training in southern (59; 42%) and northeastern (43; 31%) regions and were equally spread across all 3 years of training. One hundred (72%) respondents reported an antibiotic stewardship program (ASP) in their institution. While 86% (120/139) were able to identify the components of an ASP, 59% (82/139) either did not or were unsure if they had received antibiotic stewardship training during fellowship.Furthermore, while answering case studies, 124 (89%) respondents identified the optimal antibiotic for methicillin susceptible Staphylococcus aureus (MSSA) infection and 69 (50%) respondents chose appropriate empiric antibiotics for neonatal meningitis. Notably, fellowship training year was not significantly related to the proportion of incorrect knowledge responses (p = 0.40). Most survey respondents (81; 59%) identified small group sessions as the most useful teaching format, while others chose audit and feedback of individual prescribing behavior (52; 38%) and didactic lectures (52; 38%). Finally, ninety-five (69%) respondents preferred trainee-led ASP interventions targeting focal areas such as antifungal and surgical prophylaxis. CONCLUSION: Antibiotic stewardship is a critical part of neonatology training. Neonatology fellows report variation in access to ASP during their training. Fellows prefer dedicated trainee-led interventions and stewardship curriculum taught within small group settings to promote targeted NICU ASP. KEY POINTS: · Most neonatology programs expose trainees to internal or external antibiotic stewardship programs.. · Over half of fellow trainees are unsure about receiving targeted antibiotic stewardship training.. · Most neonatology fellows prefer a trainee-led antibiotic stewardship intervention..

Group B Streptococcus Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

BACKGROUND: This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18-26 months. METHODS: In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998-2016 at 22-28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants. RESULTS: The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02-1.45]) and uninfected infants (1.44 [1.23-1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36-2.67]), compared with uninfected infants. CONCLUSIONS: In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction. CLINICAL TRIALS REGISTRATION: NCT00063063.

Noninfectious influencers of early-onset sepsis biomarkers.

Diagnostic tests for sepsis aim to either detect the infectious agent (such as microbiological cultures) or detect host markers that commonly change in response to an infection (such as C-reactive protein). The latter category of tests has advantages compared to culture-based methods, including a quick turnaround time and in some cases lower requirements for blood samples. They also provide information on the immune response of the host, a critical determinant of clinical outcome. However, they do not always differentiate nonspecific host inflammation from true infection and can inadvertently lead to antibiotic overuse. Multiple noninfectious conditions unique to neonates in the first days after birth can lead to inflammatory marker profiles that mimic those seen among infected infants. Our goal was to review noninfectious conditions and patient characteristics that alter host inflammatory markers commonly used for the diagnosis of early-onset sepsis. Recognizing these conditions can focus the use of biomarkers on patients most likely to benefit while avoiding scenarios that promote false positives. We highlight approaches that may improve biomarker performance and emphasize the need to use patient outcomes, in addition to conventional diagnostic performance analysis, to establish clinical utility.

Intrapartum Antibiotic Exposure and Body Mass Index in Children.

BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) reduces a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). METHODS: This was a retrospective cohort study of infants (n = 223 431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure. RESULTS: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P < .0001 for all time points, ΔBMI at age 5 years 0.12 kg/m2, 95% confidence interval [CI]: .07-.16 kg/m2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P < .05 for 0.7-0.8 years, P < .0001 for all other time points) compared to other antibiotics (ΔBMI at age 5 years 0.24 kg/m2, 95% CI: .14-.34 kg/m2). Breastfeeding did not modify these associations. CONCLUSIONS: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

Neonatal blood culture inoculant volume: feasibility and challenges.

BACKGROUND: Clinicians often express concerns about poor sensitivity of blood cultures in neonates resulting from inadequate inoculant volumes. Our objective was to determine the inoculant volume sent for neonatal sepsis evaluations and identify areas of improvement. METHODS: Single-center prospective observational study of infants undergoing sepsis evaluation. Blood volume was determined by clinician documentation over 21 months, and additionally by weighing culture bottles during 12 months. Adequate volume was defined as ≥1 mL total inoculant per evaluation. For first-time evaluations, local guidelines recommend sending an aerobic-anaerobic pair with 1 mL inoculant in each. RESULTS: There were 987 evaluations in 788 infants. Clinicians reported ≥1 mL total inoculant in 96.9% evaluations. Among 544 evaluations where bottles were weighed, 93.4% had ≥1 mL total inoculant. Very low birth weight infants undergoing evaluations >7 days after birth had the highest proportion of inadequate inoculants (14.4%). Only 3/544 evaluations and 26/1011 bottles had total inoculant <0.5 mL. Ninety evaluations had <1 mL in both aerobic and anaerobic bottles despite a total inoculant volume that allowed inoculation of ≥1 mL in one of the bottles. CONCLUSIONS: Obtaining recommended inoculant volumes is feasible in majority of neonates. Measuring inoculant volumes can focus improvement efforts and improve test reliability. IMPACT: Clinicians express concern about the unreliability of neonatal blood cultures because of inadequate inoculant volume. We investigated over 900 evaluations and found >90% of evaluations have ≥1 mL inoculant. Monitoring adequacy of blood culture technique can identify areas of improvement and may allay concerns about blood culture reliability. Current recommendations for adequate inoculant volume for blood cultures are met in a majority of neonates. Areas of improvement include preterm late-onset sepsis evaluations and distribution techniques during inoculation.

Impact of Early-Onset Sepsis and Antibiotic Use on Death or Survival with Neurodevelopmental Impairment at 2 Years of Age among Extremely Preterm Infants.

OBJECTIVE: To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI. STUDY DESIGN: Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26 weeks of gestation and birth weight 401-1000 g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluid culture ≤72 hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72 hours and continued ≥5 days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26 months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants. RESULTS: Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort. CONCLUSIONS: Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI.

Prolonged duration of early antibiotic therapy in extremely premature infants.

BACKGROUND: Prolonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC. METHODS: Cohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression. RESULTS: A total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC. CONCLUSIONS: The proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.

Every three-hour versus every six-hour oral feeding in preterm infants: a randomised clinical trial.

AIM: This trial compares two oral feeding schedules, every three-hour and every six-hour oral feeding attempts, to determine which schedule allows for more rapid attainment of full oral feeding in preterm infants. METHODS: Infants born at ≤33-week gestation were randomly assigned to receive oral feeding every three hours or every six hours if feeding cues were present. The primary outcome was time to full oral feeding; secondary outcomes include respiratory and apnoea rates, growth and length of stay. RESULTS: A total of 55 infants were recruited. There was no difference between the groups in the primary or secondary outcomes. CONCLUSION: For preterm infants fed when oral feeding cues are present, an every six-hour schedule did not alter the time to full oral feeding and had no effect on rates of tachypnoea, apnoea or length of hospital stay compared to every three-hour feeding schedule. An every six-hour oral feeding schedule led to only small reductions in number of oral feeding attempts per day.

Symptomatic Postnatal Cytomegalovirus Testing among Very Low-Birth-Weight Infants: Indications and Outcomes.

Objective The objective of this study was to describe the indications for postnatal cytomegalovirus (CMV) testing among very low-birth-weight (VLBW, birth weight [BW] < 1,500 g) infants, clinical characteristics of infected infants, and adverse outcomes associated with CMV infection. Study Design This is a single-center, retrospective study of 2,132 VLBW infants from 1999 to 2013. Results In this study, 145 (6.8%) infants out of 2,132 were evaluated for postnatal CMV infection and 27 (18.6%) infants out of 145 were infected. CMV-tested infants were of significantly lower gestational age and BW compared with untested VLBW infants (p < 0.001). Respiratory decompensation and thrombocytopenia were the findings most commonly associated with infection. CMV-infected infants had significantly more exposure to mechanical ventilation and longer duration of hospitalization. Adjusting for multiple predictors of respiratory morbidity, the incidence of bronchopulmonary dysplasia (BPD) was significantly elevated among infants diagnosed with postnatal CMV infection (odds ratio, 4.0 [95% confidence interval, 1.3-12.4); p, 0.02.) Conclusion Symptomatic postnatal CMV infection was diagnosed in 1.3% of VLBW infants, most commonly among infants with BW < 1,000 g with respiratory instability and thrombocytopenia. Similar to late-onset bacterial infection, symptomatic postnatal CMV infection may be an independent contributor to the development of BPD. This possibility should be addressed in a prospective study of extremely low BW infants.

Utility of Anaerobic Blood Cultures in Neonatal Sepsis Evaluation.

BACKGROUND: Clinicians variably obtain anaerobic blood cultures as part of sepsis evaluations in the neonatal intensive care unit (NICU). Our objective was to determine if anaerobic blood culture bottles yielded clinically relevant information by either recovering pathogens exclusively or more rapidly than the concurrently obtained aerobic culture bottle in the NICU. METHODS: A retrospective cohort study of blood cultures obtained from infants admitted to the NICU from 08/01/2015-08/31/2023. Standard practice was to inoculate 2 mL of blood divided equally between an aerobic and an anaerobic culture bottle. We analyzed positive blood cultures where both aerobic and anaerobic bottles were obtained and compared pathogen recovery and time to positivity between the bottles. RESULTS: During the study period, 4599 blood cultures were obtained from 3665 infants, and 265 (5.8%) were positive. Of these, 182 cultures were sent as aerobic-anaerobic pairs and recovered pathogenic organisms. Organisms were recovered exclusively from the anaerobic bottle in 32 (17.6%) cultures. Three organisms were obligate anaerobes; the rest were facultative anaerobes including Coagulase-negative staphylococci (40.6%), Escherichia coli (15.6%), and Staphylococcus aureus (15.6%). Cultures with exclusive recovery in the anaerobic bottle were more frequently obtained ≤3 days after birth, compared to other cultures (31.3% vs. 15.3%, p=0.03). When both bottles recovered the pathogen (n=113), the anaerobic bottle had a shorter time to positivity in 76 (67.3%) cultures. CONCLUSIONS: Including anaerobic culture bottles could lead to identification of pathogens not recovered in the aerobic bottle, as well as earlier identification of pathogens.

Hospital-Onset Bacteremia Among Neonatal Intensive Care Unit Patients.

Importance: The Centers for Disease Control and Prevention plans to introduce hospital-onset bacteremia (HOB) as a health care-associated infection measure. The epidemiology and clinical characteristics of HOB among infants admitted to the neonatal intensive care unit (NICU) are unknown. Objective: To estimate the rate of HOB among infants admitted to the NICU, measure the association of HOB risk with birth weight group and postnatal age, and estimate HOB-attributable mortality. Design, Setting, and Participants: This retrospective multicenter cohort study and emulated trial from 2016 to 2021 included a convenience sample of 322 NICUs in the United States. Participants were infants admitted to participating NICUs for 4 or more days. Exposures: The primary exposures were birth weight and postnatal age. Additional exposures included small for gestational age and central line presence. Main Outcomes and Measures: The primary study outcomes were HOB and HOB-attributable mortality. Results: Of 451 443 included infants, 250 763 (55.6%) were male, 200 680 (44.4%) were female, and 62 091 (13.8%) were born 1500 g or less. Of 9015 HOB events that occurred among 8356 infants (2%) during 8 163 432 days at risk (unadjusted incidence rate, 1.1 per 1000 patient-days; 95% CI, 1.0-1.2), 4888 HOB events (54.2%) occurred in the absence of a central line. Within the first 2 weeks after birth, the HOB rate was 14.2 per 1000 patient-days (95% CI, 12.6-16.1) among infants born 750 g or less, to 0.4 events per 1000 patient-days among infants born more than 2500 g (95% CI, 0.4-0.5). Among infants born 750 g or less, the relative HOB risk decreased by 90% after day 42 compared with days 4 to 14 (incidence rate ratio [IRR], 0.10; 95% CI, 0.1-0.1). Conversely, among infants born more than 2500 g, the relative HOB risk increased by 50% after day 42 compared with days 4 to 14 (IRR, 1.5, 95% CI, 1.2-1.9). Compared with otherwise similar infants without HOB, infants with HOB had an absolute difference in attributable mortality of 5.5% (95% CI, 4.7-6.3). Conclusions and Relevance: This study found that HOB events in the NICU are associated with increased mortality. Birth weight is an important risk factor for HOB; however, the relative rate of HOB decreases over postnatal age among low-birth-weight infants and increases among infants born more than 2500 g. Identifying strategies to prevent HOB and programs to decrease HOB risk are urgently needed to reduce infant mortality.

Multiply robust causal inference of the restricted mean survival time difference.

The hazard ratio (HR) remains the most frequently employed metric in assessing treatment effects on survival times. However, the difference in restricted mean survival time (RMST) has become a popular alternative to the HR when the proportional hazards assumption is considered untenable. Moreover, independent of the proportional hazards assumption, many comparative effectiveness studies aim to base contrasts on survival probability rather than on the hazard function. Causal effects based on RMST are often estimated via inverse probability of treatment weighting (IPTW). However, this approach generally results in biased results when the assumed propensity score model is misspecified. Motivated by the need for more robust techniques, we propose an empirical likelihood-based weighting approach that allows for specifying a set of propensity score models. The resulting estimator is consistent when the postulated model set contains a correct model; this property has been termed multiple robustness. In this report, we derive and evaluate a multiply robust estimator of the causal between-treatment difference in RMST. Simulation results confirm its robustness. Compared with the IPTW estimator from a correct model, the proposed estimator tends to be less biased and more efficient in finite samples. Additional simulations reveal biased results from a direct application of machine learning estimation of propensity scores. Finally, we apply the proposed method to evaluate the impact of intrapartum group B streptococcus antibiotic prophylaxis on the risk of childhood allergic disorders using data derived from electronic medical records from the Children's Hospital of Philadelphia and census data from the American Community Survey.

Association of delivery risk phenotype with early-onset sepsis in preterm infants.

OBJECTIVE: To determine delivery risk phenotype-specific incidence of early-onset sepsis (EOS) among preterm infants. STUDY DESIGN: Retrospective cohort study of infants born <35 weeks' gestation at four perinatal centers during 2017-2021. Infants were classified into one of six delivery risk phenotypes incorporating delivery mode, presence of labor, and duration of rupture of membranes (ROM). The primary outcome was EOS incidence within the overall cohort and each risk phenotype. RESULTS: Among 2937 preterm infants, 21 had EOS (0.7%, or 7.1 cases/1000 preterm infants). The majority of EOS cases (13/21, 62%) occurred in the setting of prolonged ROM ≥ 18 h, with a phenotype incidence of 23.8 cases/1000 preterm infants. There were no EOS cases among infants born by cesarean section without ROM (with or without labor), nor via cesarean section with ROM < 18 h without labor. CONCLUSION: Delivery risk phenotyping may inform EOS risk stratification in preterm infants.

Early antibiotic exposure in very-low birth weight infants and infection risk at 3-7 days after birth.

OBJECTIVE: To determine rates of late-onset infection (LOI) during postnatal days 3-7 among preterm infants, based on antibiotic exposure during days 0-2. STUDY DESIGN: Retrospective cohort study of infants born <1500 grams and ≤30 weeks gestation, 2005-2018. We analyzed the incidence and microbiology of LOI at days 3-7 based on antibiotic exposure during postnatal days 0-2. RESULTS: The cohort included 88,574 infants, of whom 85% were antibiotic-exposed. Fewer antibiotic-exposed compared to unexposed infants developed LOI (1.5% vs. 2.1%; adjusted hazard ratio, 0.28, 95% CI 0.24-0.33). Among antibiotic-exposed compared to unexposed infants, Gram-negative (38% vs. 28%, p = 0.002) and fungal (11% vs. 1%, p < 0.001) species were more commonly isolated, and gram-positive organisms (49% vs. 70%, p < 0.001) were less commonly isolated. CONCLUSIONS: We observed low overall rates of LOI at days 3-7 after birth, but antibiotic exposure from birth was associated with lower rates, and with differing microbiology, compared to no exposure.