OBJECTIVES. Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results. METHODS. We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998–2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (≥5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death. RESULTS. Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1–36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%–85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death. CONCLUSION. Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.

OBJECTIVES. Previous studies have shown that incidence of invasive candidiasis varies substantially among centers, and previous use of broad-spectrum antibiotics is a risk factor for candidiasis in extremely low birth-weight infants. Differences in center practices, such as antibiotic strategies and the effects of these strategies on center incidence of candidiasis, are not reflected in assessments of an individual's risk of candidiasis. We evaluated the relationship between empirical antibiotic practices for extremely low birth-weight infants and center incidence of candidiasis. METHODS. We studied a cohort of extremely low birth-weight infants who survived ≥72 hours and were admitted to 1 of 12 tertiary centers between 1998 and 2001. Multivariable logistic regression was used to validate previous broad-spectrum antibiotics use as a risk factor for subsequent candidiasis in individual infants. We calculated correlation coefficients to assess the relationship between center incidence of candidiasis with antibiotic practice patterns. RESULTS. There were 3702 infants from 12 centers included, and 284 (7.7%) developed invasive candidiasis. Broad-spectrum antibiotics use was associated with candidiasis for individual infants. Center candidiasis incidence ranged from 2.4% to 20.4%. Center incidence of candidiasis was correlated with average broad-spectrum antibiotics use per infant and average use of broad-spectrum antibiotics with negative cultures per infant. CONCLUSIONS. Center incidences of invasive candidiasis differ substantially, and antibiotic practice differences are possible contributors to center variation in candidiasis risk.

Purpose of review Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Recent findings Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. Summary The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Moderate to severe hypoxic–ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime wit...