本田 仁

Background/Objectives: Japan's COVID-19 vaccination campaign achieved high coverage by 2022, yet limited national-level data has hindered evaluations of vaccine effectiveness. This study analyzed the impact of vaccines on infection outcomes while considering socioeconomic and behavioral factors in the Japanese population. Methods: A total of 19,482 individuals aged 16-81 years, who participated in both the 2021 (baseline) and 2022 (follow-up) waves of an Internet-based survey, were analyzed. Vaccine intake during the follow-up period (0/1/2+ doses) served as the exposure, while outcomes included COVID-19 diagnosis, hospitalization, and receipt of oxygenation/ventilation. Adjusted prevalence ratios (APRs) were calculated using Poisson regression models, controlling for baseline characteristics such as vaccination status, infection history, underlying medical conditions, socioeconomic factors, and preventive behaviors. Results: Overall, 81.6% of respondents received at least 1 dose of COVID-19 vaccine during the follow-up period. Among those without COVID-19 history at baseline (N = 19,182), 10.9% were diagnosed with COVID-19 in the past year, and 6.6% in the past 2 months. Respondents who received 1 or 2+ doses had lower diagnosis rates (APR = 0.76 and 0.43, respectively). For the past 2 months, only those with 2+ doses showed a significant reduction (APR = 0.51). Among 1999 diagnosed cases, those with 1 or 2+ doses showed lower hospitalization and oxygenation/ventilation likelihoods, though these differences were not statistically significant. Conclusions: The results supported the protective effect of COVID-19 vaccines against infection. Continued research is essential to further clarify the complex influence of vaccination, individual characteristics, and preventive behaviors on COVID-19 morbidity at the population level.

BACKGROUND: The present study aimed to investigate the association between the duration of anti-coronavirus disease 2019 (COVID-19) public health measures and the quality of life (QOL) and mental health of the Japanese public. METHODS: The present, nationwide, questionnaire-based, cross-sectional study was conducted in September 2021. The cumulative duration in days of anti-COVID-19 public health measures was calculated for each prefecture in the year prior to the survey, and multilevel linear regression analysis was used to determine the association between the duration of these measures and any impairment of QOL or mental health as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) and the Kessler scale (K6). RESULTS: The study included 28 118 participants from all 47 prefectures. The median duration of public health measures of all prefectures was 179 days. Long-term duration of the measures (181-365 days) was not independently associated with low EQ-5D-5L (P = 0.128) or high K6 (P = 0.179) scores after adjusting for potential confounders (Graphical Abstract). CONCLUSIONS: Prolongation of the measures may not be associated with a deterioration in the QOL or mental health of the Japanese public. Nevertheless, it may be necessary to reconsider long-term public health measures given the potential they may have to cause collateral damage, such as socioeconomic one.

BACKGROUND: Few interventional studies of catheter-associated urinary tract infection (CAUTI) have been conducted to optimize indwelling urinary catheter (IUC) use in Japan. METHODS: The nurse-led, before-after study was conducted at a tertiary care center from June 2018 through May 2022. The intervention included 1) the provision of appropriate indications for IUC use, 2) prospective feedback to the primary care providers by ward nurses on unnecessary/inappropriate IUC use with two, separate interventional phases, the first involving intensive care units (ICU) only, the second involving ICU and general wards, and 3) proactive feedback by Infectious diseases physicians in the Infection Control department to the primary care providers regarding IUC discontinuation upon discharge from the ICU. RESULTS: During the first phase involving the implementation of the intervention only in the ICU, the indwelling urinary catheter-device utilization ratio (IUC-DUR) trend in the general wards decreased by 1.5 % (P = 0.01). However, the addition of the intervention to the general wards in the second phase led to a 2 % increase in the trend (P = 0.010). The CAUTI incidence in neither the ICU nor the general wards changed significantly. CONCLUSIONS: Although providing feedback on IUC removal at discharge from the ICU and appropriate indications for urinary catheter insertion can reduce inappropriate urinary catheter use, the nurse-led intervention alone was inadequate for reducing the CAUTI incidence.

During the COVID-19 pandemic, people often modified their behaviors and performed individual infection control practices despite the uncertain effectiveness of these in preventing COVID-19. A cross-sectional study using a nationwide internet survey (Japan COVID-19 Society Internet Survey) was conducted from September 2022 through October 2022. The questionnaire consisted of individual-level social distancing behaviors and infection prevention measures, and COVID-19 vaccination status. A multivariate logistic regression was performed to determine factors associated with the diagnosis of COVID-19 in the last 2 months of the survey date. In total, 19,296 respondents were selected for the primary analysis. Of 19,296 respondents, those with COVID-19 diagnosed in the last 2 months were 1,909 (9.9%). Factors independently associated with a recent history of COVID-19 were meeting colleagues in person ≧ 1 per week (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.36-2.19, P < .001). The response of "never or rarely" to the question of taking out (ie, dining in) foods was marginally associated with a recent history of COVID-19 (aOR 1.27, 95% CI 0.99-1.63, P = .06). Most individual, infection prevention practices and behavioral modifications during the omicron variant phase of the pandemic did not substantially impact COVID-19 prevention in the community.

INTRODUCTION: Even during the endemic phase of the COVID-19 pandemic, the impact of persistent symptoms on patients and healthcare systems remains significant. Thus, a more comprehensive understanding of these symptoms is essential. METHODS: Using data from the Japan Society and New Tobacco Internet Survey conducted in February 2023, this cross-sectional study investigated the prevalence of, and changes in, persistent COVID-19 symptoms. RESULTS: In total, 21,108 individuals responded to the survey. Of these, 29.1 % (6143) had a history of COVID-19. Our analysis found that arm/leg/joint pain (adjusted odds ratio [aOR]: 1.17; 95 % confidence interval [95 % CI]: 1.03-1.33), back pain (aOR: 1.13; 95 % CI: 1.01-1.27), chest pain (aOR: 1.53; 95 % CI: 1.20-1.96), malaise (aOR: 1.14; 95 % CI: 1.02-1.28), loss of taste (aOR: 2.55; 95 % CI: 1.75-3.72), loss of smell (aOR: 2.33; 95 % CI: 1.67-3.26), memory impairment (aOR: 1.27; 95 % CI: 1.04-1.56), and cough (aOR: 1.72; 95 % CI: 1.38-2.13) were independently associated with a history of COVID-19 contracted more than two months but less than six months previously. Further, back pain (aOR: 1.24; 95 % CI: 1.04-1.47) and loss of taste (aOR: 2.28; 95 % CI: 1.24-4.21) showed independent association with COVID-19 contracted more than 12 months previously. CONCLUSIONS: Various symptoms were independently associated with a history of COVID-19. While most patients tend to recover within a year after contracting COVID-19, certain symptoms, such as back pain and loss of taste, persist longer than a year, underscoring public health concerns and emphasizing the need for health care services to support patients suffering from persistent symptoms.

OBJECTIVE: The days of therapy (DOT) metric, used to estimate antimicrobial consumption, has some limitations. Days of antibiotic spectrum coverage (DASC), a novel metric, overcomes these limitations. We examined the difference between these 2 metrics of inpatient intravenous antimicrobial consumption in assessing antimicrobial stewardship efficacy and antimicrobial resistance using vector autoregressive (VAR) models with time-series analysis. METHODS: Differences between DOT and DASC were investigated at a tertiary-care center over 8 years using VAR models with 3 variables in the following order: (1) the monthly proportion of prospective audit and feedback (PAF) acceptance as an index of antimicrobial stewardship efficacy; (2) monthly DOT and DASC adjusted by 1,000 days present as indices of antimicrobial consumption; and (3) the monthly incidence of 5 organisms as an index of antimicrobial resistance. RESULTS: The Granger causality test, which evaluates whether incorporating lagged variables can help predict other variables, showed that PAF activity contributed to DOT and DASC, which, in turn, contributed to the incidence of drug-resistant P. aeruginosa. Notably, only DASC helped predict the incidence of drug-resistant Enterobacterales. Another VAR analysis demonstrated that a high proportion of PAF acceptance was accompanied by decreased DASC in a given month, whereas increased DASC was accompanied by an increased incidence of drug-resistant Enterobacterales, unlike with DOT. CONCLUSIONS: The VAR models of PAF activity, antimicrobial consumption, and antimicrobial resistance suggested that DASC may more accurately reflect the impact of PAF on antimicrobial consumption and be superior to DOT for predicting the incidence of drug-resistant Enterobacterales.

BACKGROUND: Clinical details of long COVID are still not well understood because of potential confounding with a wide range of pre-existing comorbidities. METHODS: The present study used datasets from a nation-wide, cross-sectional, online survey. We determined which prolonged symptoms were more likely to be associated with post-COVID condition after adjusting for a wide range of comorbidities and baseline characteristics. This study also used EuroQol 5 dimensions 5-levels (EQ-5D-5L) and Somatic Symptom Scale-8 to assess health-related quality of life (QOL) and somatic symptoms in individuals with a previous history of COVID-19, defined as the diagnosis of COVID-19 made at least 2 months prior to the online survey. RESULTS: In total, 19,784 respondents were included for analysis; of these, 2,397 (12.1%) had a previous history of COVID-19. The absolute difference of adjusted prevalence of symptoms attributed to prolonged symptoms after COVID-19 ranged from -0.4 % to +2.0 %. Headache (adjusted odds ratio [aOR]: 1.22; 95% confidence interval [95% CI]:1.07-1.39), chest discomfort (aOR:1.34, 95% CI:1.01-1.77), dysgeusia (aOR: 2.05, 95% CI: 1.39-3.04), and dysosmia (aOR: 1.96, 95% CI: 1.35-2.84) were independently associated with a previous history of COVID-19. Individuals with a history of COVID-19 had lower health-related QOL scores. CONCLUSION: After adjusting for potential comorbidities and confounders, clinical symptoms, such as headache, chest discomfort, dysgeusia, and dysosmia, were found to be independently associated with a history of COVID-19, which was diagnosed two or more months previously. These protracted symptoms may have impacted QOL and the overall somatic symptom burden in subjects with a previous history of COVID-19.

BACKGROUND: The characteristics and risk factors of post-COVID-19 condition affecting health-related quality of life and the symptom burden are unclear. METHODS: The present, cross-sectional study used the JASTIS (Japan Society and New Tobacco Internet Survey) database. EQ-5D-5L and Somatic Symptom Scale-8 were used to assess health-related quality of life and somatic symptoms, respectively. The participants were classified into a no-COVID-19, COVID-19 not requiring oxygen therapy or COVID-19 requiring oxygen therapy group. First, the entire cohort was analyzed. Then, sensitivity analysis was performed after excluding patients in the no-COVID-19 group with a history of close contact with individuals known to have the disease. FINDINGS: In total, 30130 individuals (mean age: 47.8; females: 51.2%), including 539 and 805 with COVID-19 requiring and not requiring oxygen therapy, respectively, participated. The analysis of the entire cohort as well as the sensitivity analysis demonstrated that individuals with a history of COVID-19 had significantly lower EQ-5D-5L and significantly higher SSS-8 scores than those with no COVID-19 history. The group requiring oxygen therapy was associated with significantly lower EQ-5D-5L and higher SSS-8 scores than the group not requiring oxygen therapy. Propensity-score matching confirmed these results. Furthermore, two or more COVID-19 vaccinations were independently associated with high EQ-5D-5L and low SSS-8 scores (P < 0.001). CONCLUSIONS: The participants with a COVID-19 history, especially those with severe disease, had a significantly higher somatic symptom burden. Analysis after adjusting for potential confounders found that their quality-of-life was also severely affected. Vaccination is crucial to addressing these symptoms, especially in high-risk patients.

We evaluated the impact of discontinuing universal preadmission screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) on the occurrence of nosocomial clusters of coronavirus disease 2019 (COVID-19) during the SARS-CoV-2 o (omicron) variant period. No increasing trend in nosocomial clusters was observed during community-based surges before and after discontinuation. This finding supports the safety of the practice change.

BACKGROUND: Antimicrobial resistance (AMR) is a global threat with the potential to cause a significant healthcare burden. In 2016, the Japanese government issued the national action plan for AMR (NAP). Since the issuance of this plan, several studies on antimicrobial stewardship programs (ASP) have been published in Japan. We therefore performed the present systematic review of these studies to elucidate the current state of ASP and the impact of the NAP. METHODS: Medline (PubMed) and EMBASE were searched for studies published between January 2016 and the end of September 2021. ROBINS-I was used to assess the risk of bias in interventional studies, and the Newcastle-Ottawa Scale was used to assess the quality of cohort, case-control, and cross-sectional studies. RESULTS: Eighty studies, including 30 (37.5 %) interventional studies, 15 (18.8 %) database-oriented studies, and nine (11.3 %) analytical studies (one case-control study, six cohort studies, and two cross-sectional studies), were included. All the interventional studies were before-after trials, and interrupted time series analysis was commonly used to assess changes in antimicrobial consumption per intervention. Five database-related studies demonstrated decreasing antimicrobial consumption after the issuance of the NAP. CONCLUSION: Several ASP studies were published after the issuance of the NAP, suggesting that the latter promoted research into ASP. A few, database-related studies showed a positive impact of the NAP on antimicrobial consumption. However, more high-quality studies, especially interventional studies using an appropriate methodology and standardized data collection, continue to be necessary.

Objective: Infectious diseases (ID) consultation has contributed to improving outcomes in hospitalized patients. However, the timing of signing off on ID consultation varies, depending on the consulting ID physician. We studied the descriptive epidemiology of treatment-related adverse events (ADEs) occurring after the ID physician has signed off on consultation and the epidemiology and predictors of nonadherence to ID recommendations in the post-sign-off period. Methods: This retrospective cohort study was conducted at a Japanese tertiary-care center. All patients who received ID consultation between January and December 2019 and treatment recommendations for a confirmed or suspected infectious disease were included. The incidence of any treatment-related ADE after signing off, nonadherence to the final ID recommendations, and factors associated with nonadherence to the ID recommendations were identified. Results: In total, 367 patients receiving ID consultation were included. The incidence of post-sign-off events during index hospitalization was 59 (16.1%) of 367, with antimicrobial-associated ADEs accounting for 26 events (44.1%) and HAIs accounting for 13 events (22.0%). After excluding patients who discontinued treatment, nonadherence to ID recommendations was identified in 55 (15.7%) of 351 patients. Newly acquired HAIs during the index hospitalization after signing off on ID consultation was an independent risk factor for nonadherence to ID recommendations (adjusted odds ratio, 3.78; 95% confidence interval, 1.14-12.52). Conclusions: Post-sign-off events were common and led to nonadherence to ID recommendations during the post-sign-off period. Because this nonadherence occurs for various reasons, patients may require continued attention after signing off to ensure their safety.

We evaluated the impact of carbapenem shortage on antimicrobial practice and patient outcome at a tertiary care center. During the shortage, hospital antimicrobial practice could be safely managed through additional antimicrobial stewardship measures including treatment guidance and mandatory preauthorization. Antimicrobial shortage may present a unique opportunity for promoting antimicrobial stewardship.

OBJECTIVE: To evaluate antibiotic prescribing behavior (APB) among physicians with various specialties in five Asian countries. DESIGN: Survey of antibiotics prescribing behavior in three stages (initial, on-treatment, and de-escalation stages). METHODS: Participants included internists, infectious diseases (ID) specialists, hematologists, intensivists, and surgeons. Participants' characteristics, patterns of APB, and perceptions of antimicrobial stewardship were collected. A multivariate analysis was conducted to evaluate factors associated with appropriate APB. RESULTS: There were 367 participants. The survey response rate was 82.5% (367/445). For the initial stage, different specialties had different choices for empiric treatment. For the on-treatment stage, if the patient does not respond to empiric treatment, most respondents will step up to broader-spectrum antibiotics (273/367: 74.39%). For the de-escalation stage, the rate of de-escalation was 10%-60% depending on the specialty. Most respondents would de-escalate antibiotics based on guidelines (250/367: 68.12%). De-escalation was mostly reported by ID specialists (66/106: 62.26%). Respondents who reported that they performed laboratory investigations prior to empirical antibiotic prescriptions (aOR = 2.83) were associated with appropriate use, while respondents who reported ID consultation were associated with appropriate antibiotic management for infections not responding to empiric treatment (aOR = 40.87); adherence with national guidelines (aOR = 2.57) was associated with reported successful carbapenem de-escalation. CONCLUSION: This study highlights the variation in practices and gaps in appropriate APB on three stages of antibiotic prescription among different specialties. Education on appropriate investigation, partnership with ID specialist, and availability and adherence with national guidelines are critical to help guide appropriate APB among different specialties.

The incidence of seasonal infections due to respiratory viruses other than severe acute respiratory coronavirus virus 2 (SARS-CoV-2) has declined due to heightened public infection prevention measures against coronavirus disease 2019 (COVID-19). We describe an outbreak of human coronavirus OC43 infection that occurred at a long-term care facility and whose clinical features were indistinguishable from COVID-19.

COVID-19 is a viral infection and does not require antibiotics. The study aimed to elucidate a prescribing pattern of antibiotics for COVID-19. A nationwide cross-sectional study was conducted in Japan. The Diagnosis and Procedure Combinations (DPC) data was used to collect information, covering 25% of all acute care hospitals in the country. In 140,439 COVID-19 patients, 18,550 (13.21%) patients received antibiotics. Antibiotics were prescribed more often in inpatients (10,809 out of 66,912, 16.15%) than outpatients (7741 out of 73,527, 10.53%) (p < 0.001). Outpatient prescription was significantly associated with older patients (odds ratio [OR], 4.66; 95% confidence interval [CI] 4.41-4.93) and a greater Charlson index (OR with one-point index increase, 1.22; 95% CI 1.21-1.23). Inpatient prescription was significantly associated with older patients (OR 2.10; 95% CI 2.01-2.21), male gender (OR 1.12, 95% CI 1.07-1.18), a greater Charlson index (OR with one-point increase, 1.06; 95% CI 1.05-1.07), requirement of oxygen therapy (OR 3.44; 95% CI 3.28-3.60) and mechanical ventilation (OR 15.09; 95% CI 13.60-16.74). The most frequently prescribed antibiotic among outpatients was cefazolin, while that among inpatients was ceftriaxone. Antibiotic prescription is relatively low for acute COVID-19 in Japan. Antibiotic prescription was associated with older age, multi-morbidity, severe disease, and winter season.

Background: Some patients receive the diagnosis of bloodstream infection (BSI) after discharge from the emergency room (ER). Because the safety of discharging patients after a blood culture collection is unknown, the present study aimed to investigate the prevalence, outcomes, and factors associated with BSI diagnosed after ER discharge. Methods: This monocentric, case-control study compared patients who received a BSI diagnosis after ER discharge with those who were admitted for BSI. Factors associated with ER discharge after a blood culture collection were identified using multivariate logistic regression analysis. Results: Between January 2014 and December 2020, 5.5% (142/2575) of patients with BSI visiting the ER were initially discharged. This occurred more commonly during the coronavirus disease 2019 (COVID-19) pandemic in 2020. On multivariate analysis, factors independently associated with the discharge of patients with BSI were the absence of hypotension (adjusted odds ratio [aOR], 15.71 [95% confidence interval {CI}, 3.45-71.63]), absence of altered mental status in the ER (aOR, 8.99 [95% CI, 3.49-23.14]), unknown origin at ER discharge (aOR, 4.60 [95% CI, 2.43-8.72]), and low C-reactive protein (aOR, 3.60 [95% CI, 2.19-5.93]). No difference in 28-day mortality was observed between the groups. Conclusions: BSI is occasionally diagnosed after ER discharge. The prevalence of BSI diagnosed after ER discharge may have increased during the COVID-19 pandemic. Normal vital signs, unknown origin at ER discharge, and low C-reactive protein were important considerations leading to the discharge of these patients.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critically ill patients requiring endotracheal intubation and mechanical ventilation. Recently, the emergence of multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species, has complicated the selection of appropriate antimicrobials and contributed to treatment failure. Although novel antimicrobials are crucial to treating VAP caused by these multidrug-resistant organisms, knowledge of how to optimize their efficacy while minimizing the development of resistance should be a requirement for their use. RECENT FINDINGS: Several studies have assessed the efficacy of novel antimicrobials against multidrug-resistant organisms, but high-quality studies focusing on optimal dosing, infusion time and duration of therapy in patients with VAP are still lacking. Antimicrobial and diagnostic stewardship should be combined to optimize the use of these novel agents. SUMMARY: Improvements in diagnostic tests, stewardship practices and a better understanding of dosing, infusion time, duration of treatment and the effects of combining various antimicrobials should help optimize the use of novel antimicrobials for VAP and maximize clinical outcomes while minimizing the development of resistance.

Nocardia species cause a broad spectrum of infections, especially in immunocompromised patients. Given its relative rarity, data on the prognosis and distribution of nocardiosis from a large cohort are scarce. The present study aimed to scrutinize the clinical features and outcomes of nocardiosis in Japan, including 1-year mortality and microbiological data. The present multicentric, retrospective cohort study enrolled patients aged ≥18 years with nocardiosis diagnosed between January 2010 and December 2017 and recorded their clinical and microbiological characteristics. Factors associated with 1-year mortality were also determined using Cox proportional hazard analysis. In total, 317 patients were identified at 89 hospitals. Almost half (155/317, 48.9%) were receiving immunosuppressive agents, and 51 had disseminated nocardiosis (51/317, 16.1%). The 1-year all-cause mortality rate was 29.4% (80/272; lost to follow-up, n = 45). The most frequently isolated species was Nocardia farcinica (79/317, 24.9%) followed by the Nocardia nova complex (61/317, 19.2%). Selected antimicrobial agents were generally effective, with linezolid (100% susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. In Cox proportional hazard analysis, factors independently associated with 1-year mortality were a Charlson comorbidity index score of ≥5 (adjusted hazard ratio [aHR], 3.61; 95% confidence interval [CI], 1.95 to 6.71, P < 0.001) and disseminated nocardiosis (aHR, 1.79; 95%CI, 1.01 to 3.18, P = 0.047). The presence of advanced comorbidities and disseminated infection, rather than variations in antimicrobial therapy or Nocardia species, was independently associated with 1-year mortality.

Antimicrobial use during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary-care center was analyzed using interrupted time-series analysis. Among intravenous antimicrobials, the use of azithromycin and third-generation cephalosporins significantly decreased during the current pandemic. Similarly, the use of oral antimicrobials, including azithromycin and fluoroquinolones, also decreased.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccine may hold the key to ending the pandemic, but vaccine hesitancy is hindering the vaccination of healthcare personnel (HCP). We examined their perceptions of the COVID-19 vaccine and implemented an intervention to increase vaccination uptake. DESIGN: Before-and-after trial. PARTICIPANTS AND SETTING: Healthcare personnel at a 790-bed tertiary-care center in Tokyo, Japan. INTERVENTIONS: A prevaccination questionnaire was administered to HCP to examine their perceptions of the COVID-19 vaccine. A multifaceted intervention was then implemented involving (1) distribution of informational leaflets to all HCP, (2) hospital-wide announcements encouraging vaccination, (3) a mandatory lecture, (4) an educational session about the vaccine for pregnant or breastfeeding HCP, and (5) allergy testing for HCP at risk of allergic reactions to the vaccine. A postvaccination survey was also performed. RESULTS: Of 1,575 HCP eligible for enrollment, 1,224 (77.7%) responded to the questionnaire, 533 (43.5%) expressed willingness to be vaccinated, 593 (48.4%) were uncertain, and 98 (8.0%) expressed unwillingness to be vaccinated. The latter 2 groups were concerned about the vaccine's safety rather than its efficacy. After the intervention, the overall vaccination rate reached 89.7% (1,413 of 1,575), and 88.9% (614 of 691) of the prevaccination survey respondents answered "unwilling" to or "unsure" about eventually receiving a vaccination. In the postvaccination questionnaire, factors contributing to increased COVID-19 vaccination included information and endorsement of vaccination at the medical center (274 of 1,037, 26.4%). CONCLUSIONS: This multifaceted intervention increased COVID-19 vaccinations among HCP at a Japanese hospital. Frequent support and provision of information were crucial for increasing the vaccination rate and may be applicable to the general population as well.

OBJECTIVES: In Japan, most tuberculosis (TB) cases occur among individuals aged 65 years or older. However, data on in-hospital adverse events (AEs) associated with TB management, especially in high-income nations with an ageing population, are scarce. The present study aimed to scrutinize the current TB unit practices, incidence of in-hospital AEs, and predictors of in-hospital mortality. METHODS: This retrospective cohort study was conducted at a tertiary care centre in Tokyo, Japan from 2012 to 2017. Inpatients with the diagnosis of TB and aged > 18 years were included. Quality of in-hospital care and factors associated with in-hospital mortality were investigated using multivariate logistic regression analysis. RESULTS: In total, 448 patients were enrolled. The in-hospital mortality rate was 16.7% (75/448). Miliary/disseminated TB was common (59/448, 13.2%), especially in those who died (17/75, 22.7%). Factors independently associated with in-hospital mortality were a low Karnofsky performance status score on admission (score: 40-10, adjusted odds ratio [aOR]: 25.65, 95% confidence interval [CI]: 5.63-116.92 and score: 70-50, aOR: 9.47, 95% CI: 2.07-43.3), age over 89 years (aOR: 3.68, 95% CI: 1.08-12.46), Charlson Comorbidity Index > 5 (aOR: 3.56, 95% CI: 1.37-9.21), development of any healthcare-associated infection (HAI) (aOR: 2.95, 95% CI: 1.35-6.41), and development of any drug-related AE leading to discontinuation of antituberculosis agents (seven patients were unable to resume treatment with antituberculosis agents prior to death) (aOR: 2.29, 95% CI: 1.02-5.11). CONCLUSIONS: In-hospital AEs (i.e., HAIs and drug-related AEs), as well as patient-related variables, were associated with in-hospital mortality among TB patients.

<title>Abstract</title>A questionnaire was distributed to hospitals in Tokyo (N = 38) regarding their preparedness against and in-facility transmission of coronavirus disease 2019 (COVID-19). As of May 31, 2020, 284 HCP had contracted COVID-19, and in-facility COVID-19 transmission occurred at 13 hospitals, negatively impacting hospital functions and patient care.

Background: The present study assessed the impact of time-out on vancomycin use and compared the strategy's efficacy when led by pharmacists versus infectious disease (ID) physicians at a tertiary care center. Methods: Time-out, consisting of a telephone call to inpatient providers and documentation of vancomycin use >72 hours, was performed by ID physicians and clinical pharmacists in the Departments of Medicine and Surgery/Critical Care. Patients in the Department of Medicine were assigned to the clinical pharmacist-led arm, and patients in the Department of Surgery/Critical Care were assigned to the ID physician-led arm in the initial, 6-month phase and were switched in the second, 6-month phase. The primary outcome was the change in weekly days of therapy (DOT) per 1000 patient-days (PD), and vancomycin use was compared using interrupted time-series analysis. Results: Of 587 patients receiving vancomycin, 132 participated, with 79 and 53 enrolled in the first and second phases, respectively. Overall, vancomycin use decreased, although the difference was statistically nonsignificant (change in slope, -0.25 weekly DOT per 1000 PD; 95% confidence interval [CI], -0.68 to 0.18; P = .24). The weekly vancomycin DOT per 1000 PD remained unchanged during phase 1 but decreased significantly in phase 2 (change in slope, -0.49; 95% CI, -0.84 to -0.14; P = .007). Antimicrobial use decreased significantly in the surgery/critical care patients in the pharmacist-led arm (change in slope, -0.77; 95% CI, -1.33 to -0.22; P = .007). Conclusions: Vancomycin time-out was moderately effective, and clinical pharmacist-led time-out with surgery/critical care patients substantially reduced vancomycin use.

BACKGROUND: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. METHODS: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. FINDINGS: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference -1·7 [-9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [-6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI -7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. INTERPRETATION: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. FUNDING: Sanofi and Regeneron Pharmaceuticals.

The frequent prescription of antimicrobials, such as at discharge from the emergency department, calls for optimizing this practice through modifying physicians' prescribing behavior. A 1-year, multifaceted intervention implemented in an emergency department decreased the mean monthly antimicrobial prescription rate at discharge and increased the proportion of appropriate prescriptions.

INTRODUCTION: Clusters of novel coronavirus infectious disease of 2019 (COVID-19) have spread to become a global pandemic imposing a significant burden on healthcare systems. The lack of an effective treatment and the emergence of varied and complicated clinical courses in certain populations have rendered treatment of patients hospitalized for COVID-19 difficult. METHODS: Tokyo Metropolitan Tama Medical Center, a public tertiary acute care center located in Tokyo, the epicenter of COVID-19 in Japan, has been admitting patients with COVID-19 since February 2020. The present, retrospective, case-series study aimed to investigate the clinical course and outcomes of patients with COVID-19 hospitalized at the study institution. RESULTS: In total, 101 patients with COVID-19 were admitted to our hospital to receive inpatient care. Eleven patients (10.9%) received ECMO, and nine patients (8.9%) died during hospitalization after COVID-19 was diagnosed. A history of smoking and obesity were most commonly encountered among patients with a complicated clinical course. Most patients who died requested to be transferred to advanced palliative care in the early course of their hospitalization. CONCLUSIONS: Our experience of caring for these patients demonstrated a relatively lower mortality rate and higher survival rate in those with extracorporeal membrane oxygenation placement than previous reports from other countries and underscored the importance of proactive, advanced care planning in the early course of hospitalization.

The Ministry of Health, Labour and Welfare has published the Manual of Antimicrobial Stewardship (1st edition) in June 2017 to improve the prescribing practice of antimicrobials for immunocompetent adult and pediatric (both school-aged and older children) patients. Due to the increasing demand for further promoting outpatient antimicrobial stewardship, we conducted a literature and national guideline review to identify the area of need. The results of our review revealed a high antimicrobial prescription rate in the Japanese pediatric population. Furthermore, although the Japanese clinical guidelines/guidance covered the fields of almost all infectious diseases, no system exists to estimate the incidence and treatment patterns of important infectious diseases such as asymptomatic bacteriuria, skin and soft tissue infections, and dental practices in Japan. Therefore, addressing the issues of both establishing surveillance systems and the implementation of guidelines/guidance can be the next step to promote further outpatient antimicrobial stewardship.

<title>Abstract</title> The coronavirus disease 2019 (COVID-19) pandemic has influenced current infection control practices in the healthcare setting. We surveyed 74 hospitals in Japan regarding changes in their infection control practices or policies between 2020 and the present. We found that the current hospital infection control practices for COVID-19 are adequate.

Abstract Purulent mastitis due to Streptococcus pneumoniae is extremely rare and is thought to be transmitted to the mother from the respiratory tract of the child during breastfeeding. We report herein a case of a 37-year-old, pregnant, Japanese patient in her third trimester with systemic lupus erythematosus (SLE) who presented with bacteremic pneumococcal mastitis despite the absence of lactation. Previous studies suggested that a marked susceptibility to S. pneumoniae among patients with SLE may play an important role in the development of severe infections due to this organism. Clinicians should be aware of this susceptibility and the importance of pneumococcal vaccination for patients with SLE.

The shortage of antimicrobials poses a global health threat. In Japan, for instance, the current, critical shortage of cefazolin, a first-line agent for the treatment of common infectious diseases and surgical antimicrobial prophylaxis, has had a substantial impact on inpatient care. A shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, with the unintended consequence of militating against antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. Although there is global awareness of the shortage of crucial antimicrobials, action to resolve this problem, especially with a view to preventing antimicrobial resistance and promoting antimicrobial stewardship, has been slow, possibly due to the failure to appreciate the urgency of the dilemma. A comprehensive plan for stabilizing antimicrobial access and international collaboration to secure a continuous supply of essential antimicrobials are urgently needed.

Background: Postprescription review and feedback (PPRF) is one of the most common strategies in antimicrobial stewardship program (ASP) intervention. However, disagreements between the prescribers and ASP personnel can occur. The aim of the present study was to identify the factors associated with nonadherence to PPRF intervention. Methods: The present retrospective nested case-control study was performed at a tertiary care center, which has been conducting a once-weekly PPRF for carbapenems and piperacillin/tazobactam since 2014. Nonadherence to ASP recommendations was defined as the failure of the primary care team to modify or stop antimicrobial therapy 72 hours after the issuance of PPRF recommendations. Factors associated with nonadherence to PPRF intervention were identified using multivariate logistic regression analysis. Results: In total, 2466 instances of PPRF in 1714 cases between April 2014 and September 2019 were found. The nonadherence rate was 5.9%, and 44 cases were found in which carbapenems or piperacillin/tazobactam continued to be used against PPRF recommendations. Factors associated with nonadherence to PPRF recommendations were a previous history of hospitalization within 90 days (adjusted odds ratio [aOR], 2.62; 95% confidence interval [CI], 1.18-5.81) and a rapidly fatal McCabe score at the time of PPRF intervention (aOR, 2.87; 95% CI, 1.18-6.98). A review of the narrative comments in the electronic medical records indicated that common reasons for nonadherence were "the patient was sick" (n = 12; 27.3%) and "the antimicrobial seemed to be clinically effective" (n = 9; 20.5%). Conclusions: Nonadherence to PPRF recommendations was relatively uncommon at the study institution. However, patients with a severe disease condition frequently continued to receive broad-spectrum antimicrobials against PPRF recommendations. Understanding physicians' cognitive process in nonadherence to ASP recommendations and ASP interventions targeting medical subspecialties caring for severely ill patients is needed to improve ASP.

BACKGROUND: Our goal was to evaluate the 5-year sustainability of a multimodal intervention that included a prize to the hospital with the highest overall hand hygiene adherence rates among health care workers. METHODS: We conducted an observational study in 3 Japanese tertiary care hospitals using unobtrusive direct observation of physician and nurse hand hygiene adherence. Observations were performed by a trained observer on inpatient medical, surgical, intensive care, and emergency units. The primary outcome was hand hygiene adherence rates before patient contact. Secondary outcomes were health care worker survey responses to a World Health Organization (WHO) questionnaire on hand hygiene practices. RESULTS: Hand hygiene adherence rates had improved significantly after the introduction of a multimodal intervention (based on principles recommend by the WHO) in 2012 and 2013 (from 18.0% pre-intervention to 32.7% 6 months post-intervention; P < .001). No significant changes were found in hand hygiene adherence in these hospitals 5 years after the original intervention (31.9% 5 years after intervention; P = .53); however, substantial variability in hand hygiene adherence by unit and health care worker type was noted. CONCLUSIONS: A multimodal hand hygiene initiative achieved sustained improvement in hand hygiene adherence in 3 Japanese hospitals 5 years after the original intervention.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.