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To evaluate the safety and effectiveness of evidence-based antibiotic stewardship in a neonatal unit in China. The study period consisted of two phases, one retrospective (the baseline period, January to December 2018, and the transition period, January 2019 to August 2020) and one prospective intervention period (September 2020 to August 2021). During the prospective period, evidence-based antibiotic stewardship was applied to neonates with suspected infections, pneumonia, and culture-negative sepsis. The antibiotic stewardship included the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis. The change in antibiotic use measured by days of therapy per 1000 patient-days between the baseline and intervention period was analyzed. Safety outcomes included reinitiation of antibiotics within 14 days, length of stay, occurrence of late-onset sepsis and necrotizing enterocolitis (Bell stage ≥ II), multidrug-resistant organism infections, and mortality. A total of 7705 neonates were enrolled during the baseline (n = 4804) and the intervention periods (n = 2901). The total antibiotic usage during the baseline period was 771 days of therapy per 1000 patient-days, while that was 525 days of therapy per 1000 patient-days during the intervention period, indicating a 32% decrease in antibiotic consumption. No significant difference in safety outcomes was observed between the baseline and intervention period (P > 0.05), whereas the length of stay was longer during the intervention period (P < 0.001). Conclusion: The evidence-based antibiotic stewardship can safely and effectively reduce antibiotic use and shorten the duration of therapy in the neonatal unit. What is Known: • Overuse of antibiotics has been associated with adverse events in neonates, including necrotizing enterocolitis, multidrug-resistant organism infections, and death. • More clinical effectiveness evidence is needed to support antibiotic stewardship of neonates in China. What is New: • Using prospective audit, targeted stewardship interventions, this study shows that a 32% reduction in overall antibiotic consumption was achieved safely. • Implementation of evidence-based neonatal antibiotic stewardship, including the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis, is safe and effective among newborns in a developing country. [ABSTRACT FROM AUTHOR]

Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of β-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of β-thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with β-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with β-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Ρ = 5.1 × 10−4). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in β-thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF. [ABSTRACT FROM AUTHOR]

Enterococcus is a major cause of important nosocomial infections. Linezolid, the first member of an entirely new class of antibiotics (oxazolidinones), is effective against serious infections caused by Enterococcus . However, resistance to linezolid has been discovered throughout the world rapidly. From 2011 to 2013, nine linezolid-resistant E. faecalis isolates were collected and the possible mechanisms of linezolid resistance, including mutations in domain V of 23S rRNA genes and in ribosomal proteins L3 and L4, and the multiresistance gene cfr , were investigated. Furthermore, an epidemiological survey of the nine linezolid-resistant E. faecalis isolates was performed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and DiversiLab. The three methods were compared to evaluate their merits and demerits, respectively. We failed to find the resistance mechanisms that have been revealed in recent years by PCR and sequencing analysis in the linezolid-resistant E. faecalis . Epidemiological investigation suggested that a small-scale outbreak of linezolid-resistant E. faecalis emerged in neurosurgery ICU from March to May of 2013. DiversiLab was a reliable typing tool and a suitable alternative to PFGE because it was as discriminatory as PFGE and better than MLST. [ABSTRACT FROM AUTHOR]