Antimicrobial Stewardship Programs in Neonates: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is a significant contributor to mortality and morbidity; however, the uncontrolled use of antimicrobials is associated with significant adverse effects. Our objective with this article is to review the components of neonatal antimicrobial stewardship programs (ASP) and their effects on clinical outcomes, cost-effectiveness, and antimicrobial resistance. METHODS: We selected randomized and nonrandomized trials and observational and quality improvement studies evaluating the impact of ASP with a cutoff date of May 22, 2023. The data sources for these studies included PubMed, Medline, Embase, Cochrane CENTRAL, Web of Science, and SCOPUS. Details of the ASP components and clinical outcomes were extracted into a predefined form. RESULTS: Of the 4048 studies retrieved, 70 studies (44 cohort and 26 observational studies) of >350 000 neonates met the inclusion criteria. Moderate-certainty evidence reveals a significant reduction in antimicrobial initiation in NICU (pooled risk difference [RD] 19%; 95% confidence interval [CI] 14% to 24%; 21 studies, 27 075 infants) and combined NICU and postnatal ward settings (pooled RD 8%; 95% CI 6% to 10%; 12 studies, 358 317 infants), duration of antimicrobial agents therapy (pooled RD 20%; 95% CI 10% to 30%; 9 studies, 303 604 infants), length of therapy (pooled RD 1.82 days; 95% CI 1.09 to 2.56 days; 10 studies, 157 553 infants), and use of antimicrobial agents >5 days (pooled RD 9%; 95% CI 3% to 15%; 5 studies, 9412 infants). Low-certainty evidence reveals a reduction in economic burden and drug resistance, favorable sustainability metrices, without an increase in sepsis-related mortality or the reinitiation of antimicrobial agents. Studies had heterogeneity with significant variations in ASP interventions, population settings, and outcome definitions. CONCLUSIONS: Moderate- to low-certainty evidence reveals that neonatal ASP interventions are associated with reduction in the initiation and duration of antimicrobial use, without an increase in adverse events.

Antibiotic use in Canadian neonatal intensive care units: a national survey for developing antimicrobial stewardship targets.

A survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.

Primary coenzyme Q10 deficiency-7: expanded phenotypic spectrum and a founder mutation in southern Chinese.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.

Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay.

BACKGROUND: We report here clinical, cytogenetic and molecular data for a pair of monochorionic diamniotic twins with paternal isodisomy for chromosome 19. Both twins presented with dysmorphic features and global developmental delay. This represents, to our knowledge, the first individual human case of paternal uniparental disomy for chromosome 19 (UPD19). METHODS: Whole-exome sequencing, together with conventional karyotype and SNP array analysis were performed along with genome-wide DNA methylation array for delineation of the underlying molecular defects. RESULTS: Conventional karyotyping on amniocytes and lymphocytes showed normal karyotypes for both twins. Whole-exome sequencing did not identify any pathogenic sequence variants but >5000 homozygous exonic variants on chromosome 19, suggestive of UPD19. SNP arrays on blood and buccal DNA both showed paternal isodisomy for chromosome 19. Losses of imprinting for known imprinted genes on chromosome 19 were identified, including ZNF331, PEG3, ZIM2 and MIMT1. In addition, imprinting defects were also identified in genes located on other chromosomes, including GPR1-AS, JAKMP1 and NHP2L1. CONCLUSION: Imprinting defects are the most likely cause for the dysmorphism and developmental delay in this first report of monozygotic twins with UPD19. However, epigenotype-phenotype correlation will require identification of additional individuals with UPD19 and further molecular analysis.