Within a randomized prospective pilot study of preterm infants born at less than 33 weeks’ gestation, weekly fecal samples from 19 infants were collected and metabolomic analysis was performed. The objective was to evaluate for differences in fecal metabolites in infants exposed to antibiotics vs. not exposed to antibiotics in the first 48 h after birth. Metabolomics analysis was performed on 123 stool samples. Significant differences were seen in the antibiotics vs. no antibiotics groups, including pathways related to vitamin biosynthesis, bile acids, amino acid metabolism, and neurotransmitters. Early antibiotic exposure in preterm infants may alter metabolites in the intestinal tract of preterm infants. Broader multi-omic studies that address mechanisms will guide more prudent antibiotic use in this population.

With the current advancements in DNA sequencing technology, the limiting factor in long-read metagenomic assemblies is now the quantity and quality of input DNA. Although these requirements can be met through the use of axenic bacterial cultures or large amounts of biological material, insect systems that contain unculturable bacteria or that contain a low amount of available DNA cannot fully utilize the benefits of third-generation sequencing. The citrus greening disease insect vector Diaphorina citri is an example that exhibits both of these limitations. Although endosymbiont genomes have mostly been closed after the short-read sequencing of amplified template DNA, creating de novo long-read genomes from the unamplified DNA of an insect population may benefit communities using bioinformatics to study insect pathosystems. Here all four genomes of the infected D. citri microbiome were sequenced to closure using unamplified template DNA and two long-read sequencing technologies. Avoiding amplification bias and using long reads to assemble the bacterial genomes allowed for the circularization of the Wolbachia endosymbiont of Diaphorina citri for the first time and paralleled the annotation context of all four reference genomes without utilizing a traditional hybrid assembly. The strategies detailed here are suitable for the sequencing of other insect systems for which the input DNA, time, and cost are an issue.

Objective: We aim to assess the feasibility of a pragmatic randomized trial of antibiotics vs. no antibiotics in symptomatic premature infants after birth. Most premature infants are exposed to antibiotics after birth without evidence of benefit or harm for this practice. No study to date has attempted to randomize premature infants to antibiotics vs no antibiotics after birth. Study Design: Infants <33 weeks’ gestation admitted to the University of Florida Neonatal Intensive Care Unit were assigned to one of three groups after birth: (A) high risk – antibiotics indicated (B) low risk – antibiotics not indicated (C) eligible for un-blinded randomization (no antibiotics vs antibiotics). The primary outcome is a composite of serious adverse events including (necrotizing enterocolitis, late onset sepsis, bronchopulmonary dysplasia, and death). Odds ratios (and 95% CI’s) were calculated to compare adverse event rates between the two randomized groups. Results: 186 subjects were enrolled (98 infants and 88 mothers) were enrolled over a 2-year period. 56% of infants (n=55) were randomized; 48% of infants randomized to the no antibiotics arm were switched and received antibiotics within the first 48 hours after birth. Serious adverse events were not significantly different between the randomization arms. Conclusion: This is the first prospective randomized trial of antibiotics vs no antibiotics after birth in symptomatic premature infants. The results of this trial establish a framework of feasibility for a larger multicentered trial that is needed to evaluate the risks and benefits of routine antibiotic exposure in premature infants.