Evaluation of long-term pharmacist-led prospective audit and feedback in antimicrobial stewardship: An 8-year study.

BACKGROUND: Limited research has evaluated the long-term outcomes of prospective audit and feedback (PAF) led by pharmacists. We assessed pharmacist-led PAF processes and outcome measures over 8 years. METHODS: This study was conducted at a single public hospital in Japan. Between 2014 and 2021, pharmacists conducted weekday PAFs for hospitalized patients and annually evaluated the process and outcome measures. The endpoints included detection of drug-resistant bacteria, drug susceptibility rates, duration of antimicrobial therapy, and proportion of long-term administration. RESULTS: Among inpatients, methicillin-resistant Staphylococcus aureus significantly decreased from 50.9% in 2014 to 32.8% in 2021 (P < .001). The susceptibility rate of Pseudomonas aeruginosa to meropenem significantly increased from 91.2% in 2014 to 94.4% in 2021 (P < .001) and levofloxacin increased from 84.9% in 2014 to 89.3% in 2021 (P < .001). Antimicrobial therapy duration did not differ significantly between 2014 and 2016, but decreased significantly from 2017 onwards (P < .001), except in 2018. The number of patients receiving intravenous antimicrobials for >10 days decreased significantly between 2014 and 2021 (P < .001). CONCLUSIONS: Long-term continuous PAF interventions by pharmacists contribute to improving and maintaining process and outcome indicators and prevent the spread of drug-resistant bacteria.

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens.

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3-year-old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia.

The structure and binding mode of interleukin-18.

Interleukin-18 (IL-18), a cytokine formerly known as interferon-gamma- (IFN-gamma-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-gamma production, Fas-mediated cytotoxicity and developmental regulation of T-lymphocyte helper type I. We determined the solution structure of IL-18 as a first step toward understanding its receptor activation mechanism. It folds into a beta-trefoil structure that resembles that of IL-1. Extensive mutagenesis revealed the presence of three sites that are important for receptor activation: two serve as binding sites for IL-18 receptor alpha (IL-18Ralpha), located at positions similar to those of IL-1 for IL-1 receptor type I (IL-1RI), whereas the third site may be involved in IL-18 receptor beta (IL-18Rbeta) binding. The structure and mutagenesis data provide a basis for understanding the IL-18-induced heterodimerization of receptor subunits, which is necessary for receptor activation.

Predominant expression of 950delCAG of IL-18R alpha chain cDNA is associated with reduced IFN-gamma production and high serum IgE levels in atopic Japanese children.

BACKGROUND: We previously reported that serum IgE levels were negatively correlated with the amount of IFN-gamma produced by phytohemagglutinin-stimulated or IL-12-stimulated PBMCs and that one of the mechanisms of the pathogenesis of atopy was the reduced IFN-gamma production, which led to upregulated IgE production. OBJECTIVE: IL-18 is also known to be a strong inducer of IFN-gamma production. However, it has not yet been determined whether IL-18 is associated with atopic disease. METHODS: We investigated the response to IL-18 or IL-12 stimulation and the sequence of IL-18 receptor (IL-18R) alpha chain cDNA in 41 nonatopic controls and 39 atopic patients. RESULTS: Serum IgE level was negatively correlated with IFN-gamma production by PBMCs stimulated with IL-18. The IL-18R alpha chain cDNA of atopic patients was sequenced. We identified a 3-base deletion of the IL-18R alpha chain cDNA (950delCAG ), which was generated by alternative splicing, as determined on the basis of genomic sequence data for the IL-18R alpha chain gene. PBMCs with the predominant expression of 950delCAG significantly showed the reduced IFN-gamma production after IL-18 stimulation. There was a significant difference in the expression pattern of the IL-18R alpha chain transcript between the atopic patients and the nonatopic controls. CONCLUSION: According to these results, the dominant expression of the 950delCAG transcript of IL-18R alpha chain cDNA, which was associated with reduced IFN-gamma production by IL-18 stimulation and high serum IgE levels, is predisposition to some atopic diseases.