BackgroundCefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin with activity against a wide variety of Gram-negative bacteria including carbapenem-resistant strains. We previously reported that CFDC is efficiently transported into Pseudomonas aeruginosa via iron transporter PiuA. In this study, we examined frequency of resistance of P. aeruginosa to CFDC, and investigated the resistance mechanisms of appeared colonies.MethodsFrequency of resistance (FoR) was determined by plating an overnight culture of P. aeruginosa PAO1 on Mueller–Hinton Agar containing 4× or 10×MIC of CFDC or ceftazidime (CAZ). Appeared colonies were analyzed by whole-genome sequencing (WGS) to identify genomic mutations. The mRNA expression was determined by real-time RT-PCR, and pyoverdine production was determined by MALDI-TOF/MS and expression of outer membrane protein was analyzed by SDS–PAGE and proteomic analysis.ResultsThe FoR to CFDC was 2.9 × 10–8 and <7.1 × 10–8, which were lower than those to CAZ (3.1 × 10–7 and 3.4 × 10–8) in the conditions of 4× and 10×MIC, respectively. MIC of CFDC against CFDC-derived mutant increased from 0.5 μg/mL (MIC against PAO1) to 2 μg/mL, and MICs of CAZ did not increase. In the case of CAZ-derived mutant, MICs of CAZ increased from 1 μg/mL (MIC against PAO1) to 16 μg/mL or higher, though MIC of CFDC did not increase, suggesting no cross-resistance between CFDC and CAZ. WGS identified mutations in upstream regions of pvdS (pvdS mutant), which regulates pyoverdine synthesis, or fecI (fecI mutant), which regulates the synthesis of iron transporter FecA contributing to the transport of iron citrate. The pvdS expression and pyoverdine production in the pvdS mutant were more than 4- and 6-fold higher than those in PAO1, respectively. The expression of fecA in the fecI mutant was more than ninefold higher than that in PAO1.ConclusionThe MIC increase of CFDC against P. aeruginosa occurred due to the mutation of iron transporter-related genes. The resistance acquisition risks should be low as the frequency of resistance to CFDC was lower and the MIC increase of CFDC against the mutants was smaller than that of CAZ. In addition, no cross-resistance between CFDC and CAZ was observed.Disclosures A. Ito, Shionogi & Co., Ltd.: Employee, Salary. T. Nishikawa, Shionogi & Co., Ltd.: Employee, Salary. R. Ishii, Shionogi & Co., Ltd.: Employee, Salary. M. Kuroiwa, Shionogi & Co., Ltd.: Employee, Salary. Y. Ishioka, Shionogi & Co., Ltd.: Employee, Salary. N. Kurihara, Shionogi & Co., Ltd.: Employee, Salary. I. Sakikawa, Shionogi & Co., Ltd.: Employee, Salary. T. Ota, Shionogi & Co., Ltd.: Employee, Salary. M. Rokushima, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, SHIONOGI & CO., LTD.: Employee, Salary. T. Sato, SHIONOGI & CO., LTD.: Employee, Salary. Y. Yamano, SHIONOGI & CO., LTD.: Employee, Salary.

Background Adolescent health promotion is important in preventing risk behaviors and improving mental health. Health promotion during adolescence has been shown to contribute to the prevention of late onset of the mental health disease. However, scalable interventions have not been established yet. Objective This study was designed to test the efficacy of two adolescent health promotion interventions: a well-care visit (WCV) with a risk assessment interview and counseling and self-monitoring with a smartphone cognitive behavioral therapy (CBT) app. Our hypothesis was that participants who had received both WCV and the CBT app would have better outcomes than those who had received only WCV or those who had not received any intervention. We conducted a prospective multi-institutional randomized controlled trial. Methods Participants were 217 adolescents aged 13-18 years. They were randomly divided into two intervention groups (WCV group and WCV with CBT app group) and a nonintervention group. WCV comprised a standardized physical examination along with a structured interview and counseling for youth risk assessment, which was designed with reference to the Guideline for Health Supervision of Adolescents of Bright Futures. A smartphone-based CBT program was developed based on the CBT approach. The CBT app comprised a 1-week psychoeducation component and a 1-week self-monitoring component. During the CBT program, participants created several self-monitoring sheets based on the CBT model with five window panels: event, thoughts, feelings, body response, and actions. The primary outcome was the change in scores for depressive symptoms. Secondary outcomes included changes in scores for self-esteem, quality of life, self-monitoring, and an adolescent health promotion scale. These outcomes were evaluated at baseline and at 1, 2, and 4 months after baseline. The exploratory outcome was the presence of suicidal ideation during the observation period. Intervention effects were estimated using mixed effect models. Results In total, 94% (204/217) of the participants completed the 4-month evaluation. Both intervention groups showed a significant effect in the form of reduced scores for depressive symptoms at 1 month in high school students; however, these effects were not observed at 2 and 4 months. The intervention effect was significantly more predominant in those scoring above cutoff for depressive symptoms. There was significantly less suicidal ideation in the intervention groups. As for secondary outcomes, there was significant increase in health promotion scale scores at the 4-month follow-up among junior high school students in the WCV group. Moreover, the CBT app was significantly effective in terms of obtaining self-monitoring skills and reducing depressive symptoms. Conclusions Although adolescent health promotion interventions may have short-term benefits, the frequency of WCV and further revision of the CBT app should be considered to evaluate long-term effectiveness. Trial Registration University Hospital Medical Information Network Clinical Trials Registry UMIN 000036343; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041246

Background Suicide is the leading cause of death among Japanese adolescents. However, knowledge gaps regarding contemporary demographics and factors associated with suicidality among Japanese adolescents are a major concern. This study examined the prevalence of suicidality among Japanese adolescents and investigated associated factors. Methods A population-based questionnaire survey investigating general health was administered to 22,419 adolescents aged 13–18 years. The 29-item questionnaire covered emotional status, family function, cyberbullying, suicidality, and stressors (e.g., relationships with parents/friends, school performance, and sexual identity). We conducted multiple logistic regression analysis to identify factors associated with suicidality in this population. Results The prevalence of suicidal ideation was 21.6% in males and 28.5% in females, and that of attempted suicide was 3.5% in males and 6.6% and in females. Bullying and stress related to family relationships had the strongest associations with suicidality. Exposure to cyberbullying had the highest odds ratio for both junior high (3.1, 95% confidence interval [CI] 2.1–4.4) and high school students (3.6, 95% CI 2.5–5.3). Other factors significantly associated with suicidality were sex, emotional status, and stress about relationships with friends, sexual identity, school records, and academic course. Adolescents accessed a variety of resources to cope with stressors, with the Internet being the most common resource consulted. Conclusions Suicidality is commonly experienced among Japanese adolescents. Although there are many associated risk factors, cyberbullying is of particular concern. Recognition of factors associated with adolescent suicidality will inform further research and suicide prevention efforts for healthcare providers and families.

Background Autism spectrum disorder (ASD) and feeding and eating disorders (FEDs) such as anorexia nervosa (AN) are strongly linked as evidenced by frequent comorbidity and overlapping traits. However, eating and social behaviors are shaped by culture, so it is critical to examine these associations in different populations. Moreover, FEDs are heterogeneous, and there has been no examination of autistic traits in avoidant/restrictive food intake disorder (ARFID). Methods Therefore, we investigated the prevalence of ASD and autistic traits among Japanese children with AN (n = 92) or ARFID (n = 32) from a prospective multicenter cohort study using the Autism Spectrum Quotient Children’s version (AQC) and Children’s Eating Attitudes Test (ChEAT26). Results ASD prevalence was high in both AN and ARFID (16.3 and 12.5%, respectively). The AN group exhibited significantly higher scores on all AQC subscales than an age-matched healthy control (HC) group, but there were no significant correlations between AQC scores and ChEAT26 scores. In the AFRID group, AQC scores did not differ from HCs, but significant correlations were found between total AQC and ChEAT26 scores and between several AQC and ChEAT26 subscales. Conclusions Both the AN and ARFID groups had high prevalence rates of ASD. The AN group showed a significantly higher degree of autistic traits than the HC group; however, no difference was found between the ARFID and HC groups. Clinicians need to be aware of these rates when working with children with ED.