FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

Extracting the latent needs of dementia patients and caregivers from transcribed interviews in japanese: an initial assessment of the availability of morpheme selection as input data with Z-scores in machine learning.

BACKGROUND: Given the increasing number of dementia patients worldwide, a new method was developed for machine learning models to identify the 'latent needs' of patients and caregivers to facilitate patient/public involvement in societal decision making. METHODS: Japanese transcribed interviews with 53 dementia patients and caregivers were used. A new morpheme selection method using Z-scores was developed to identify trends in describing the latent needs. F-measures with and without the new method were compared using three machine learning models. RESULTS: The F-measures with the new method were higher for the support vector machine (SVM) (F-measure of 0.81 with the new method and F-measure of 0.79 without the new method for patients) and Naive Bayes (F-measure of 0.69 with the new method and F-measure of 0.67 without the new method for caregivers and F-measure of 0.75 with the new method and F-measure of 0.73 without the new method for patients). CONCLUSION: A new scheme based on Z-score adaptation for machine learning models was developed to predict the latent needs of dementia patients and their caregivers by extracting data from interviews in Japanese. However, this study alone cannot be used to assign significance to the adaptation of the new method because of no enough size of sample dataset. Such pre-selection with Z-score adaptation from text data in machine learning models should be considered with more modified suitable methods in the near future.

Patient factors impacting localization of popliteal artery before total knee arthroplasty.

PURPOSE: Intraoperative injury to the popliteal artery (PA) should be avoided during total knee arthroplasty (TKA). This study was performed to clarify the preoperative localization of the PA and the patient factors that impact its localization as a preventive measure. METHODS: Ninety-seven patients (110 knees; 18 men, 79 women) with osteoarthritis who underwent primary TKA were retrospectively reviewed. Preoperative sagittal magnetic resonance imaging was used to measure the distance between the PA and the closest point at three levels: the femoral epicondyle (DPF), the tibial articular surface (DPAS), and the posterior tibial cortex (DPT). All variables are expressed in millimeters as median (interquartile range). RESULTS: The median distance was 10.35 (7.90-12.34) mm for DPF, 6.32 (5.12-8.57) mm for DPAS, and 3.76 (2.28-5.26) mm for DPT. Body height and weight showed weak correlations with DPF (r = 0.324, p < 0.001 and r = 0.207, p = 0.03, respectively). DPF was smaller in women [9.82 (7.64-12.23) mm] than in men [11.27 (10.26-12.75) mm] (p = 0.004). A larger flexion angle and range of motion showed a weak negative correlation with DPT (r = - 0.282, p = 0.003 and r = - 0.236, p = 0.016, respectively). Multiple regression analysis revealed that DPF was related to body height (ß = 0.341, p < 0.001) and that DPT was related to the flexion angle (ß = - 0.264, p = 0.005). CONCLUSIONS: Special attention should be paid to women with a small physique on the femoral side and/or patients with a large flexion angle on the tibial side as a strategy to prevent PA-related complications.

Positive effect of total knee arthroplasty on progression of arteriosclerosis evaluated by cardio-ankle vascular index.

INTRODUCTION: Physical function is expected to improve with an increase in physical activity owing to improvement in knee joint pain after total knee arthroplasty (TKA). This study was performed to evaluate the impact of TKA on arteriosclerosis by measuring the cardio-ankle vascular index (CAVI) before and after surgery. MATERIALS AND METHODS: In total, 206 consecutive patients undergoing unilateral TKA were investigated. The CAVI, an index of the overall stiffness of the artery from the origin of the aorta to the ankle, was used to evaluate the degree of arteriosclerosis. The CAVI of the TKA side and non-TKA side was compared before and 1 year after TKA. RESULTS: There were no differences in the CAVI before and after TKA on the TKA side and non-TKA side, although these values should have worsened at 1 year compared with preoperative values. The CAVI, which did not differ between the two sides preoperatively, differed significantly between the two sides postoperatively (p = 0.013). A generalized linear model showed no interaction between each time point and the measured sides in terms of the CAVI. The relationship between the preoperative CAVI and the difference between the preoperative and postoperative CAVI were examined, showing that R = - 0.428 (p < 0.001) for the TKA side and R = - 0.416 (p < 0.001) for the non-TKA side (significant negative correlation). CONCLUSIONS: The lack of significant age-related deterioration over time on both sides suggests that TKA may slow the progression of arteriosclerosis, especially on the operated side. The effect of TKA was found to be greater with a higher CAVI (i.e., more advanced arteriosclerosis).

Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan: Comparison with the first surveillance report.

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 µg/ml (2 µg/ml), 1 µg/ml (0.5 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.125 µg/ml (0.063 µg/ml), 0.125 µg/ml (0.125 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.031 µg/ml (0.031 µg/ml), 0.25 µg/ml (0.125 µg/ml), and 0.016 µg/ml (0.008 µg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.

Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility.

A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be ß-lactamase-producing ampicillin resistant strains, while 20.8% were ß-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were ß-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum ß-lactamase-producing E. coli was 14.3%.

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

Characteristics of hidden blood loss following hybrid total knee arthroplasty.

BACKGROUND: Hidden blood loss (HBL) unrecognized by the usual practice of assessing intraoperative loss and postoperative drainage comprises a considerable proportion of total blood loss (TBL) during primary total knee arthroplasty (TKA). However, HBL has not been adequately investigated in hybrid TKA (uncemented femur, cemented tibia). The purpose of this study was to clarify the amount and influential factors of HBL in hybrid TKA. METHODS: A consecutive series of 151 knees in 137 patients with knee osteoarthritis who underwent hybrid TKA were retrospectively evaluated. We examined the correlations between HBL and various factors of concern for their effects on TBL, including age, sex, body weight (BW), body height, body mass index, operation time, tourniquet time, and visible blood loss (VBL) in three periods (intraoperative: VBL1; until 3 h postoperatively: VBL2; from 3 h to 1 day postoperatively: VBL3). RESULTS: Median (interquartile range) HBL and TBL were 528 (388, 711) mL and 725 (582, 926) mL, respectively. HBL relative to TBL (H/T) was 73%. There were weak correlations between HBL and BW (r = 0.249, p = 0.002) and between HBL and VBL3 (r = -0.261, p = 0.001). Multivariate analyses confirmed a positive correlation between HBL and BW (ß = 0.296, p < 0.001) and a negative correlation between HBL and VBL3 (ß = -0.270, p < 0.001). CONCLUSIONS: Hybrid TKA showed comparable values of HBL and H/T to those reported for cemented TKA. Therefore, management strategies for HBL in hybrid TKA can follow the same protocols used for cemented TKA. High BW and low VBL3 may be predictors of postoperative HBL in hybrid TKA.

Histopathological and immunohistochemical features of proliferative lesions in the pituitary pars distalis of rats.

Pituitary proliferative lesions derived from the endocrine cells of the pars distalis are frequently encountered and adenomas/carcinomas are a common cause of death in standard 2-year carcinogenicity studies using various rat strains, especially Sprague-Dawley. This report describes the immunohistochemical characteristics of pituitary tumors derived from the pars distalis in rats. Prolactin (PRL)-containing tumors are the most common, with PRL/growth hormone (GH) dual positive tumor masses (PRL/GH co-positive tumor masses) being more prevalent than only PRL-positive tumor masses (PRL single-positive tumor masses). GH-containing tumors are relatively numerous and many of these are also PRL/GH co-positive tumor masses. TSH-containing tumors are common in females. PRL-containing tumors have been shown to increase the incidence of hyperlactation in males and mammary adenomas/adenocarcinomas in females, suggesting that these masses are functional tumors.

Morphological analyses of nephrin expression in progressive glomerulonephropathy of common marmosets.

In this study, we focused on nephrin, one of the key molecules within the slit diaphragm of podocytes, as although there have been reports on its expression in humans and rats, their presence in common marmosets has not been reported. We investigated nephrin expression and changes in glomeruli, depending on the development of spontaneous progressive glomerulonephropathy in common marmosets. Nineteen common marmosets at two to ten years of age were evaluated. The kidney was examined by microscopy with hematoxylin and eosin and immunohistochemical staining for nephrin. The lesions were classified into three grades according to a renal lesion grading system reported previously. The nephrin-positive area was measured by morphometric analysis, and the nephrin-positive ratio was calculated. Nephrin expression was observed along the glomerular capillary loop in a continuous linear pattern in renal lesion grades 0 to 2 and either discontinuous linear or coarse granular pattern in grade 3. Nephrin expression tended to decrease significantly depending on the grade of renal lesions. Alteration in nephrin expression has been suggested to play an important role in the progression of renal lesions.

Caregiver self-efficacy and associated factors among caregivers of patients with dementia with Lewy bodies and caregivers of patients with Alzheimer's disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is characterized by neuropsychiatric symptoms, which can be distressing to caregivers. However, little is known about their subjective distress in terms of caregiver self-efficacy. Thus, we examined the differences in caregiver self-efficacy and their associated factors between DLB and Alzheimer's disease (AD) caregivers. METHODS: We conducted a comprehensive questionnaire for DLB and AD caregivers. Caregiver self-efficacy was evaluated using three domains (Self-Efficacy for Obtaining Respite: SE-OR, Self-Efficacy for Responding to Disruptive Patient Behaviours: SE-RDPB, Self-Efficacy for Controlling Upsetting Thoughts about Caregiving: SE-CUT) of the Revised Scale for Caregiving Self-Efficacy (RSCSE). In addition, data on the following features of caregivers were assessed: depression, sleep disturbance, caregiver burden, executive function, loneliness, social support, and distress associated with neuropsychiatric symptoms. The patients were assessed for general cognitive tasks, executive function, and neuropsychiatric symptoms. RESULTS: Compared with AD caregivers, DLB caregivers experienced a significantly higher burden in terms of not only various clinical factors, but also all three domains of caregiver self-efficacy. Among the caregiver-associated factors, different domains were predictors of self-efficacy in DLB and AD caregivers (distress due to sleep disturbances in DLB patients; distress due to delusions in AD patients). Among the patient-associated factors, different domains were also predictors of self-efficacy in DLB and AD caregivers (sleep disturbances in DLB patients; delusions in AD patients). Among both the caregivers and the patients, executive function was a significant predictor of one RSCSE domain (SE-CUT). CONCLUSIONS: A reduction in caregiver self-efficacy may contribute to a severe subjective burden among DLB caregivers. Furthermore, two neuropsychiatric symptoms (delusions and sleep disturbances) affected caregiver self-efficacy differently depending on whether care was being provided to a DLB or AD patient. Understanding the association between specific neuropsychiatric symptoms and caregiver self-efficacy may be useful for conducting interventions for DLB patients.

Immunohistochemical Characteristics of Thymomas and Hyperplastic Lesions in Wistar Hannover Rats.

Previously, we investigated the higher incidence of hyperplastic lesions and thymomas and histopathological resemblance of cortex-medullary structures between thymomas and normal thymuses in Wistar Hannover (WH) rats. Thymomas had pale-staining cell foci (PA) similar to medulla but without lymphocytes. Here, we focused on the differences in cytokeratin (CK) expression in the thymic epithelia of the cortex and medulla and compared the structures of thymomas and normal thymuses. Thymomas, hyperplastic lesions, and normal thymuses obtained from background studies of WH rats were stained with antibodies against CK14, CK18, and CD20. In normal thymuses, the epithelial cells were positive for CK14 in the medulla and subcapsular area and for CK18 in the cortex, B-cells were positive for CD20 in the medulla. In thymomas, the epithelial cells were positive for CK14 in the medullary differentiation (MD) areas and for CK18 in the cortex-like lymphocyte rich and PA, and B-cells were positive for CD20 in the MD areas.

The third national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from complicated urinary tract infection patients.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 41.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.5% and 0.6%, respectively.