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Rapid diagnostic tests (RDTs) significantly impact disease treatment strategy. In Japan, information on the use of RDTs for patients with COVID-19 is limited. Here, we aimed to investigate the RDT implementation rate, pathogen detection rate, and clinical characteristics of patients positive for other pathogens by using COVIREGIJP, a national registry of hospitalized patients with COVID-19.A total of 42,309 COVID-19 patients were included. For immunochromatographic testing, influenza was the most common (n = 2881 [6.8%]), followed by Mycoplasma pneumoniae (n = 2129 [5%]) and group A streptococcus (GAS) (n = 372 [0.9%]). Urine antigen testing was performed for 5524 (13.1%) patients for S. pneumoniae and for 5326 patients (12.6%) for L. pneumophila.The completion rate of M. pneumonia loop-mediated isothermal amplification (LAMP) testing was low (n = 97 [0.2%]). FilmArray RP was performed in 372 (0.9%) patients; 1.2% (36/2881) of patients were positive for influenza, 0.9% (2/223) for the respiratory syncytial virus (RSV), 9.6% (205/2129) for M. pneumoniae, and 7.3% (27/372) for GAS. The positivity rate for urine antigen testing was 3.3% (183/5524) for S. pneumoniae and 0.2% (13/5326) for L. pneumophila. The positivity rate for LAMP test was 5.2% (5/97) for M. pneumoniae. Five of 372 patients (1.3%) had positive FilmArray RP, with human enterovirus being the most frequently detected (1.3%, 5/ 372).The characteristics of patients with and without RDTs submission and positive and negative results differed for each pathogen. RDTs remain an important diagnostic tool in patients with COVID-19 in whom coinfection with other pathogens needs to be tested based on clinical evaluation.

Anterior nasal sampling (AN) might be more convenient for patients than NP sampling to diagnose coronavirus disease. This study investigated the feasibility of rapid antigen tests for AN sampling, and the factors affecting the test accuracy.This single-center prospective study evaluated one qualitative (ESP) and two quantitative (LUMI and LUMI-P) rapid antigen tests using AN and NP swabs. Symptomatic patients aged 20 years or older, who were considered eligible for reverse-transcription quantitative polymerase chain reaction using NP samples within 9 days of onset were recruited. Sensitivity, specificity, and positive and negative concordance rates between AN and NP samples were assessed for the rapid antigen tests. We investigated the characteristics that affected the concordance between AN and NP sampling results.A total of 128 cases were recruited, including 28 positive samples and 96 negative samples. The sensitivity and specificity of AN samples using ESP were 0.81 and 1.00, while those of NP samples were 0.94 and 1.00. The sensitivity of AN and NP samples was 0.91 and 0.97, respectively, and specificity was 1.00, for both LUMI and LUMI-P. The positive concordance rates of AN to NP sampling were 0.87, 0.94, and 0.85 for ESP, LUMI, and LUMI-P, respectively. No factor had a significant effect on the concordance between the sampling methods.ESP, LUMI, and LUMI-P showed practical diagnostic accuracy for AN sampling compared to NP sampling. There was no significant factor affecting the concordance between AN and NP sampling for these rapid antigen tests.

Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited.A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19.During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84]).Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods.

Background This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. Methods Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. Results A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5–64.9%; mean age: 35.3–37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: −0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. Conclusions Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. Clinical Trials Registration Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350)

Antimicrobial resistance (AMR) is a major threat to global health requiring continuous development of new antimicrobial agents. Antimicrobial research and development (RD) should be promoted in the pharmaceutical industry and academia to ensure sustainable patient access to new treatment options and reduce the global AMR burden.This review describes the historical challenges in novel antimicrobial drug development in Japan, current national efforts to promote the development, and proposals to effectively manage future AMR pandemics. Literature searches were performed in the PubMed database (from inception to January 2022).RD activities in the antimicrobial space in Japan have been insufficient due to multiple factors, including unfavorable cost-profit balance and differences in regulatory requirements between Japan and Western countries. However, the situation is improving with the implementation of the Japanese AMR action plan, drug RD programs led by the Japan Agency for Medical Research and Development, and efforts of regulatory agencies in the United States, Europe, and Japan in aligning and expediting the clinical development process. Further actions during the interpandemic period will strengthen antimicrobial RD, including international and interdisciplinary collaboration, continued funding and investment with the national government's leadership, and fostering of new-generation academic research leaders.

Information regarding the clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in children under the Omicron variant predominant period is still limited.A nationwide retrospective cohort study was conducted. Pediatric COVID-19 patients (18 years of age) hospitalized between August 1, 2021 and March 31, 2022 were enrolled. Epidemiological and clinical characteristics between the Delta variant predominant period (August 1 to December 31, 2021) and the Omicron variant predominant period (January 1 to March 31, 2022) were compared.During the study period, 458 cases in the Delta predominant period and 389 cases in the Omicron predominant period were identified. Median age was younger (6.0 vs. 8.0 years, P = 0.004) and underlying diseases were more common (n = 65, 16.7% vs. n = 53, 11.6%) in the Omicron predominant period than those in the Delta variant predominant era. For clinical manifestations, fever ≥38.0 °C at 2 to13 years old, sore throat at ≥ 13 years, and seizures at 2 to13 years old were more commonly observed, and dysgeusia and olfactory dysfunction at ≥ 6 years old were less commonly observed in the Omicron variant predominant period. The number of patients requiring noninvasive oxygen support was higher in the Omicron predominant period than that in the Delta predominant period; however, intensive care unit admission rates were similar and no patients died in both periods.In the Omicron variant predominant period, more pediatric COVID-19 patients experienced fever and seizures, although the overall outcomes were still favorable.

Reimbursements for pharmacist interventions and infectious disease teams have recently been introduced in Japan. Arbekacin (ABK) is used to treat pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus, and therapeutic drug monitoring (TDM) is recommended. This study aimed to clarify the trend in TDM implementation for ABK over time and the factors associated with TDM implementation using a claims database.Data of patients aged ≥15 years who received ABK for ≥3 consecutive days between 2010 and 2019 were extracted from a large Japanese medical claims database. The proportion of reimbursements claimed for TDM, pharmacist interventions, and the setup of infectious disease teams for each year were calculated. The factors associated with TDM implementation were identified using multivariate logistic regression analysis.The proportion of TDM implementation for ABK increased by 9.1% from 2010 to 2019, but it remained less than 40% throughout this period. The proportion of TDM implementation was higher in patients who claimed reimbursements for pharmacist interventions than in patients who did not. Logistic regression analysis showed that the stationing of pharmacists in wards and long-term ABK treatment were significantly associated with TDM implementation.From 2010 to 2019, the proportion of TDM implementation for ABK was significantly low. Moreover, the factors associated with TDM implementation were clarified. An environment wherein pharmacists can help implement TDM for patients receiving ABK would be beneficial.

Pathogens and Global Health, 117(2), pp.101-103; 2023

Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza.The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted.Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors.Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989).

This study investigated the impact of the COVID-19 pandemic on antimicrobial use (AU) trends in Japan in 2020 and explored its potential effects on appropriate AU. Using nationwide antimicrobial sales data, we examined the annual and monthly trends in AU from 2016-2020 according to the AWaRe classification (Access and Watch categories) and administration route (oral and injectable). To analyze the possible impact of the COVID-19 pandemic on AU, seasonal autoregressive integrated moving average (SARIMA) models were used to predict AU in 2020 (based on the trends from 2016-2019) under the assumption that the pandemic did not occur. We observed a substantial reduction in AU in 2020 compared with preceding years. In addition, the reductions in AU for total antimicrobials and Watch category antimicrobials were greater than predicted regardless of administration route. These results suggest that the COVID-19 pandemic contributed to the observed reductions in AU, but it is also possible that the changes reflect recent efforts to improve AU. Continued AU surveillance and research are needed to optimize prescribing practices through appropriate antimicrobial stewardship.

Background Post-artemisinin delayed hemolysis (PADH) is a serious complication in patients who recover from severe malaria after receiving artemisinin-based combined therapy (ACT), including artemether-lumefantrine. In Japan, among the antimalarial drugs recommended by the World Health Organization (WHO) guideline for severe malaria, intravenous quinine gluconate is available only in 29 designated hospitals, and intravenous artesunate is unavailable. Therefore, oral artemether-lumefantrine is occasionally administered as an alternative, even though it may be a suboptimal treatment. In non-endemic settings like Japan, a lack of knowledge of malaria and the side effects, such as post-artemisinin delayed hemolysis caused by the ACT, can have critical consequences. Like our patient, being a primigravida in the early stages of pregnancy is a serious risk factor for severe malaria and must be carefully monitored. Case presentation This report describes a severe case of imported Plasmodium falciparum malaria complicated by fetal loss and prolonged anemia, requiring frequent blood transfusions. The patient was a previously healthy pregnant Japanese female in her 30 s. She developed a high fever 2 days after returning from Nigeria. The patient fulfilled the severe malaria criteria by WHO. On arrival, an abdominal ultrasound incidentally revealed a fetus of 5 week gestational age with a heartbeat in the uterus. Given her pregnancy and the severity of the disease, she was administered intravenous quinine 16 mg/kg as a loading dose. However, the second dose of quinine was not administered due to frequent vomiting and QTc prolongation. We initiated treatment with oral artemether-lumefantrine, and clearance of parasitemia was confirmed by microscopic observation on day 4. Miscarriage was noted on day 6 after admission. Moreover, the patient became feverish again up to 39 °C, and from days 14 to 22, the patient required multiple blood transfusions due to PADH. On day 40, follow-up was discontinued as the hemoglobin level exceeded 10 g/dL. Conclusions In patients who recover from severe malaria after ACT treatment, monitoring the hemoglobin level for at least a month is strongly recommended for prompt identification of PADH. Travelers to malaria-endemic countries, especially primigravida women, should be provided with adequate information on the risk and prevention of infection.

Background Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. Methods This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. Results Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days. Conclusions In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.

Background Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. Methods Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. Results Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. Conclusions Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.

BackgroundEpidemiological data regarding differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination are scarce.MethodsWe repeatedly assessed the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants.ResultsA total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (per 30 days [95% CI]) was slower after 3-dose (25% [23–26]) than 2-dose (36% [35–37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9–22]); 3-dose plus infection (21% [17–25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3-dose, except for sex (lower in female participants) and immunosuppressant use. Antibody waning was faster in older participants, females, and alcohol drinkers after 2-dose, whereas it did not differ after 3-dose across except sex.ConclusionsThe 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection further enhanced its durability. The antibody levels at a given time point and waning speed after 2-dose differed across background factors; however, these differences mostly diminished after 3-dose.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Clinical features of COVID-19 are diverse, and a useful tool for predicting clinical outcomes based on clinical characteristics of COVID-19 is needed. This study examined the laboratory values and trends that influence mortality in hospitalised COVID-19 patients. Data on hospitalised patients enrolled in a registry study in Japan (COVID-19 Registry Japan) were obtained. Patients with records on basic information, outcomes, and laboratory data on the day of admission (day 1) and day 8 were included. In-hospital mortality was set as the outcome, and associated factors were identified by multivariate analysis using the stepwise method. A total of 8860 hospitalised patients were included. The group with lactate dehydrogenase (LDH) levels >222 IU/L on day 8 had a higher mortality rate compared to the group with LDH levels ≤222 IU/L. Similar results were observed in subgroups formed by age, body mass index (BMI), underlying disease, and mutation type, except for those aged

Several commercial nucleic acid amplification tests (NAAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. We used six kits available in Japan in 13 NAAT-positive specimens with crossing point values >36 and 7 NAAT-negative specimens from patients with coronavirus disease (COVID-19); their results were compared. Specimens positive in ≥2 assays were considered true positive and examined for concordance with specimen results. The SARS-CoV-2 Detection Kit -Multi- (Toyobo M) (Toyobo, Osaka, Japan) using extracted RNA had the highest concordance (κ 1.00). This was followed by the cobas® SARS-CoV-2 (Cobas) (Roche, Basel, Switzerland) (κ 0.79). There was a weak correlation between number of negative results for each kit and days between onset and testing (Spearman rank correlation: ρ= 0.44; p

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in the stool samples of patients with coronavirus disease 2019 (COVID-19), and this virus can be transmitted via the oral-fecal route. However, there are only few reports on the viral load in the stool samples. In this pilot study, we aimed to evaluate the clinical characteristics and viral load of SARS-CoV-2 in the stool samples of 13 patients with confirmed COVID-19 using pepper mild mottle virus as a control, which has been proposed as a potential marker of human feces contamination in the environmental water bodies. SARS-CoV-2 RNA was detected in the stool samples of four patients (31%), and among them, three exhibited symptoms of diarrhea. One patient who suffered from long-term diarrhea (22 days) exhibited highest level of viral RNA in the stool sample (8.28 log10 copies/g). However, we could not harvest SARS-CoV-2 from the stool sample of any patient, even after culturing with VeroE6/TMPRESS2 cells for four weeks. Our results suggest that SARS-CoV-2 RNA can be detected in the stool samples of patients with COVID-19 suffering from diarrhea. However, further studies elucidating the relationship between SARS-CoV-2 viral load in the stool samples and symptoms of diarrhea in large cohorts and upon adjusting other causative factors and virus infectivity are still warranted.

Background Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. Methods A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score–matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. Results During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21–23.069] and 3.871 [1.201–12.477], respectively). Conclusions Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.

Introduction In response to global outbreaks of infectious diseases, the need for support from organizations such as the World Health Organization Global Outbreak Alert and Response Network (GOARN) is increasing. Identifying the obstacles and support needs for applicants could increase GOARN deployments from Japan. Methods This cross-sectional study involved a web-based, self-administered questionnaire survey targeting Japanese participants in the GOARN Tier 1.5 training workshop, held in Tokyo in December 2019. Results All 47 Japanese participants in the workshop responded to the survey. Most responders were male and in their 30s and 40s. Participants specialized in case management (42.6%), infection prevention and control (25.6%), epidemiology and surveillance (19.1%). Only two participants (4.6%) had experienced a GOARN deployment. Their motivations for joining the GOARN training workshop were “Desire to be part of an international emerging infectious disease response team” (44.6%), “Interest in making an international contribution” (19.1%), and “Interest in working for the Japanese government in the field of international infectious diseases” (14.9%). Obstacles to GOARN deployments were “Making time for deployments” (45.7%) and “Lack of required professional skills and knowledge” (40.4%). The support needs for GOARN deployments constituted “Periodic simulation training” (51.1%), “Financial support during deployments” (44.7%), and “Technical support for deployments” (40.4%). Conclusions Our study revealed the obstacles and support needs of Japanese candidates for GOARN deployment. Making time and upskilling for GOARN deployment were the main obstacles. More practical training (like GOARN Tier 2.0) with other supports are needed. The national framework is desirable to realize these supports.

To describe the trend of cumulative incidence of coronavirus disease 19 (COVID-19) and undiagnosed cases over the pandemic through the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants among healthcare workers in Tokyo, we analysed data of repeated serological surveys and in-house COVID-19 registry among the staff of National Center for Global Health and Medicine. Participants were asked to donate venous blood and complete a survey questionnaire about COVID-19 diagnosis and vaccine. Positive serology was defined as being positive on Roche or Abbott assay against SARS-CoV-2 nucleocapsid protein, and cumulative infection was defined as either being seropositive or having a history of COVID-19. Cumulative infection has increased from 2.0% in June 2021 (pre-Delta) to 5.3% in December 2021 (post-Delta). After the emergence of the Omicron, it has increased substantially during 2022 (16.9% in June and 39.0% in December). As of December 2022, 30% of those who were infected in the past were not aware of their infection. Results indicate that SARS-CoV-2 infection has rapidly expanded during the Omicron-variant epidemic among healthcare workers in Tokyo and that a sizable number of infections were undiagnosed.

Background While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. Methods We describe incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected 3 matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the 2 groups. Results No COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and participants had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. Conclusions Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant outbreak. The result points to the importance of infection-control measures in the post-vaccination era, irrespective of immunogenicity profile.

Secretory dimeric immunoglobulin A (IgA) plays an important role in preventing the invasion of foreign objects by its neutralizing activity on mucosal surfaces, while monomeric serum IgA is thought to relate to the phagocytic immune system activation. Here, we report that individuals with the novel coronavirus disease (COVID-19) developed both systemic neutralizing IgG (nIgG) and IgA (nIgA) active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

This study aimed to clarify the relationship between carbapenem consumption and clinical outcome using the diagnosis procedure combination (DPC) payment system database (2020) published by the Ministry of Health, Labour, and Welfare of Japan. This study divided 5316 medical facilities subject to aggregation into five facilities and calculated the median values, including facility characteristics, clinical outcomes, and carbapenem consumption. Next, a correlation analysis was performed between carbapenem consumption and clinical outcome, as well as a multiple regression analysis between carbapenem consumption as the dependent variable and clinical outcome, bed size, and proportion of patients by disease as independent variables. Additionally, three clinical outcomes available from the DPC payment system database were selected, including cure, readmission within 4 weeks, and the average length of stay. This study revealed no relationship between carbapenem consumption and clinical outcome in university hospitals and university hospital-equivalent community hospitals; however, a relationship was suggested in the community, DPC-prepared, and non-DPC hospitals. University hospitals and university hospital-equivalent community hospitals with a high consumption of carbapenems may need to reconsider the classification because of the limited number of facilities in this classification.

We analyzed 2462 episodes of suspected catheter-related bloodstream infection (CRBSI). The sensitivity, specificity, and positive and negative predictive values for detecting Candida CRBSI by gram staining of catheter tips were 66.1%, 99.4%, 84.4%, and 98.4%, respectively. Gram staining may be useful for the early detection of Candida CRBSI.

Background Neutralizing antibody therapy such as casirivimab/imdevimab is known to significantly reduce the viral load of SARS-CoV-2, but there is limited study on the clinical prognosis of neutralizing antibody therapy, especially in Asia, and the dynamics of cytokines is unknown worldwide. Several cytokines have been investigated as biomarkers to predict oxygen demand, among which CCL17 and INF3 have received approved and covered by the national health insurance in Japan. Methods Between July 2021 - December 2021, patient’s demographic, laboratory, radiological findings, prognosis, and cytokine kinetics (IFN-λ3, CCL17) at National Center for Global Health and Medicine, Tokyo, Japan, were analyzed using medical charts and serum samples. Univariate analysis was performed using Fisher's exact probability test and Mann-Whitney U test to evaluate the clinical characteristics of the group with oxygen demand compared with those of the group without oxygen demand. Results Thirty-four patients were analyzed. The median age of the cohort was 57.5 years (IQR 52.8-67.3), and 25 (73.5%) were male. Eight patients (23.5%) had been fully vaccinated and three patients (8.8%) had been vaccinated once. The severity of disease before casirivimab/imdevimab was asymptomatic in two (5.9%), mild in 12 (35.3%), moderate in 20 (58.8%) cases. Of the 17 cases in which mutant strains were identified, 16 were delta strains. The IFN-λ3 level (pg/mL) before casirivimab/imdevimab was significantly higher (7.6 vs. 17.2, p = 0.005), while the CCL17 level (pg/mL) was significantly lower (148.8 vs. 64.2, p = 0.036) in the group with oxygen demand during the therapeutic course compared to those in the group without oxygen demand. After casirivimab/imdevimab was administered, the IFN-λ3 level decreased to a median of 0.0 (IQR 0.0-0.3), while the CCL17 level increased to median of 220.3 (IQR 135.8-304.8), with no statistically significant differences between both groups (Figure 1). None of the patients became seriously ill. Figure 1A and 1B show the changing of the cytokine dynamics in COVID-19 patients who were treated with casirivimab/imdevimab on IFN-λ3 level and CCL17 level, respectively. Conclusion There was a statistically significant difference between IFN-λ3 and CCL17 levels before casirivimab/imdevimab in both groups. Our results suggest that casirivimab/immudevimab may improve the clinical prognosis for COVID-19 patients with delta strains. Disclosures All Authors: No reported disclosures.

Background Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (VO). Oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, but data on pyogenic VO are scarce. Methods This retrospective study included adult patients treated with oral cephalexin as the completing treatment for pyogenic VO with bacteremia due to MSSA at the National Center for Global Health and Medicine Hospital, Japan from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing the improvement in symptoms and laboratory and imaging results after intravenous (IV) administration of antimicrobial agents and after oral cephalexin treatment, using a 5-point scale (Table). A score of 4 or 5 indicated treatment success. Results This study included 15 patients (8 [53%] females), with median age 75 years (interquartile range [IQR], 67.5–80.5), median body weight 57.0 kg (IQR, 45.5–62.5), and median Charlson comorbidity index score 2 (IQR, 0–4). Ten patients (67%) had lesions in the lumbar spine. Six patients had lesions at multiple sites (cervical and thoracic, n=1; cervical and lumbar, n=2; thoracic and lumbar, n=1; and lumbar and sacral, n=2). Twelve patients (80%) had spinal abscesses and four (27%) had remote abscesses, but none had concomitant endocarditis. In 11 patients with normal renal function, 1,500–2,000 mg/day of cephalexin was administered. Surgical intervention was performed in five cases (33%). The median duration of IV antibiotics, cephalexin, and total treatment was 36 (IQR, 32–61; range, 21–86), 29 (IQR, 19–82; range, 8–251), and 86 (IQR, 59–125; range, 37–337) days, respectively. Majority patients (≥80%) received either cefazolin or ceftriaxone as IV therapy. Two patients used oral antimicrobials other than cephalexin outside of the cephalexin treatment period. Treatment success rate after cephalexin therapy was 87%. None of the patients had recurrence during a median follow-up of 119 days (IQR, 48.5-350). Conclusion In patients with bacteremic VO due to MSSA, completing treatment with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective IV antimicrobial therapy is provided. Disclosures All Authors: No reported disclosures.

Background Pharmacists play an important role in infection control and antimicrobial stewardship teams in hospitals and the community. The need for education on antimicrobial resistance (AMR) and clinical infectious diseases (CID) is increasing. However, the status of Japanese pharmaceutical education on CID and AMR is unclear. Methods We conducted a nationwide cross-sectional survey of pharmaceutical department in Japanese universities between February and March 2022. Data on the following were collected using questionnaires: 1) basic information; 2) number of faculty members with experience in CID; 3) lecture times for CID and AMR; 4) self-evaluation of CID and AMR education; and 5) the most important issues in CID and AMR education. Descriptive analyses were conducted. Results Among the 74 participating universities, 44 (59.5%) universities responded. The median number [IQR] of faculties of infectious disease education was 7 [4–12], and clinical faculties was 3 [1–6]. Twenty-seven (62.8%) of the universities had faculties with clinical experience in infectious diseases. Lectures time for CID and AMR varied among the universities. Respondents indicated that CID and AMR lectures were insufficient, compared to microbiology basic lectures. Additionally, insufficient lecture time and specialists were the most common responses as the most important issues in CID and AMR education. University background and questions regarding CID and AMR lectures (N=44) Boxplot of lectures time for clinical infectious disease and antimicrobial resistance education Self-evaluation of clinical infectious disease and antimicrobial resistance education Conclusion This study revealed that educational status and resources for CID and AMR education varied widely, and that practical lectures on CID and AMR may be insufficient. We suggest that the entire core curriculum and resources, including the number of faculties, needs to be examined and improved. The most important issues in clinical infectious disease and antimicrobial resistance education. Disclosures All Authors: No reported disclosures.

Background Japan has one of the most aging societies in the world. Urinary tract infection (UTI) is a common disease in the elderly, and the incidence of hospitalization owing to UTI is increasing with the aging population. Here, we examined the length of hospital stay, differences in the Barthel index (BI), activities of daily living score (ADLs) at admission and discharge, and medical costs of UTI in elderly patients. Methods We retrospectively included hospitalized UTI patients in our center between January 1, 2013 and March 31, 2019. The inclusion criteria were as follows: (1) urine culture positive for Escherichia coli (over 104 colony forming units/mL) within 48 h of admission, and (2) the presence of at least one of the following: fever ≥ 38°C, costovertebral angle tenderness, suprapubic tenderness, and dysuria at the time of admission. We classified the enrolled patients into four groups according to age: young adults (20–64 years), pre-old (65–74 years), old (75–84 years), and super-old (≥ 85 years). Patient characteristics were compared across groups using the Mann–Whitney U test, Fisher’s exact test, and Kruskal-Wallis test. The Bonferroni corrected P < 0.05 was considered statistically significant. Results This study enrolled 393 cases, including 112 (28.4%) young adults, 72 (18.3%) pre-old, 130 (33.2%) old, and 79 (20.1%) super-old. The lengths of hospital stay were 10.8, 17.9, 17.2, and 21.6 days in young adults, pre-old, old, and super-old, respectively (P < 0.05). Differences in the BI were 1.2, 4.2, 5.2, and 5.2 in young adults, pre-old, old, and super-old, respectively (P < 0.05). However, no significant differences in these values were noted among the pre-old, old, and super-old groups. The medical costs were 6,054, 8,310, 10,129, and 12,577-USD (1USD = 128 yen) in young adults, pre-old, old, and super-old, respectively (P < 0.05). Nevertheless, a comparison of the medical costs per day showed no significant differences among the groups. Conclusion UTI in elderly patients were associated with ADLs decline, longer hospital stays, and higher medical costs than those in younger patients; however, no significant differences were found among those aged ≥ 65 years. Disclosures Sho Saito, MD, PhD, DAIICHI SANKYO: Grant/Research Support|EVEC: Grant/Research Support|EVEC: Patents obtained through collaborative research|SHIONOGI: Grant/Research Support|Takeda: Advisor/Consultant.

Background Two years have passed since the global outbreak of COVID-19 began. Vaccines and many therapeutic agents have now been developed, and treatment is being conducted in accordance with guidelines. In general, it takes a long time for guidelines to be established, as a large amount of clinical data is required. Therefore, in the early and middle stages of an epidemic, treatment is often based on experience at individual centers. This study focuses on two drugs, Favipiravir and Steroid, and investigates how trends in drug use changed in different regions. Methods We compared the proportion of drug administered patients in the COVID-19 Registry Japan (COVIREGI-JP). Data from four COVID-19 epidemic waves, from January 2020 to June 2021, were included for the analysis. To compare regional trends, 10 categories were used based on existing classifications. In addition, Tokyo and Osaka were accounted for separately, for a total of 12 regions. Severity of each case was divided into mild, moderate 1, moderate 2 and severe based on the condition on admission, and the proportion of Favipiravir or Steroid administered cases was calculated for moderate 2 and severe cases. Results Favipiravir was administered to more than 50-100% of patients in the first wave. Thereafter, it declined nationwide, with sharp falls in Tokyo (34.9%, 16.5% and 4.3%) and Osaka (48.8%, 41.8% and 8.0%). In Hokkaido, on the other hand, 82.4%, 53.7% and 59.8% of the cases still continued to receive Favipiravir. In the first wave, Steroid was administered to 20-40% of cases. The proportion gradually increased, with 50-80% in the second wave, and 85.5% in Tokyo, 93.4% in Osaka and 90.2% in Hokkaido in the fourth wave, the majority of cases. Changes over time in the proportions of cases treated with Favipiravir and Steroid in each region. The top four and middle four panels show the proportion of cases treated with Favipiravir and Steroid, respectively. The lower epi-curve shows the number of COVID-19 cases in Japan. Conclusion We confirmed that the more effective treatment was rapidly spreading throughout the country. More information is available in areas with a large number of cases, such as Tokyo and Osaka, and in facilities that see a large number of cases. On the other hand, it may be difficult for smaller facilities or facilities that do not see many COVID-19 cases. Information from registry studies would be useful in making more effective treatments available earlier and more widely. We believe that further use of COVIREGI-JP would promote standardization of treatment. Disclosures All Authors: No reported disclosures.

Introduction The automated quantitative antigen test (QAT), which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is suitable for mass screening. However, its diagnostic capability differentiated by time from onset and potential contribution to infectivity assessment have not been fully investigated. Methods A retrospective, observational study using nasopharyngeal swab specimens from coronavirus disease (COVID-19) inpatients was conducted using LumipulseⓇ SARS-CoV-2 antigen test. Diagnostic accuracy was examined for the early (up to 10 days after onset) and late (over 10 days after onset) stages. Time-course QAT changes and reverse‐transcription quantitative polymerase chain reaction tests results were displayed as locally estimated scatterplot smoothing curve, and receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cutoff value for differentiating the early and late stages. Results We obtained 100 specimens from 68 COVID-19 patients, including 51 early-stage and 49 late-stage specimens. QAT sensitivity and specificity were 0.82 (0.72–0.90) and 0.95 (0.75–0.99) for all periods, 0.93 (0.82–0.98) and 1.00 (0.39–1.00) for the early stage, and 0.66 (0.48–0.82) and 0.93 (0.69–0.99) for the late stage, respectively. The ROC analysis indicated an ideal cutoff value of 6.93 pg/mL for distinguishing early-from late-stage specimens. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting the late stage were 0.76 (0.61–0.87), 0.76 (0.63–0.87), 0.76 (0.61–0.87), and 0.76 (0.63–0.87). Conclusions QAT has favorable diagnostic accuracy in the early COVID-19 stages. In addition, an appropriate cutoff point can potentially facilitate rapid identification of noncontagious patients.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Introduction Many articles have reported that the coronavirus disease 2019 (COVID-19) causes coagulation abnormalities and pulmonary thrombosis, contributing to a poorer prognosis. The study aimed to evaluate whether pre-admission anticoagulation and antiplatelet therapy prevented severe COVID-19 illness or not. Materials and methods We conducted a study to determine whether taking antiplatelet or anticoagulation agents before admission affected the severity on admission using a large nationwide cohort of hospitalized COVID-19 patients in Japan. We analyzed a large nationwide cohort of hospitalized COVID-19 patients in Japan from February 9 to July 31, 2020. Results and conclusion A total of 4265 patients from 342 facilities in Japan were included. Their use was associated with a slight reduction in the disease severity on admission in a propensity score-matched analysis which controlled for underlying diseases. However, this difference was not statistically significant.

Background The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. Methods A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18–64, 65–74, 75–89, and ≥90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: Results The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged ≥90 years at very high risk. The mortality rates of patients aged ≥75 years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. Conclusions The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients ≥75 years old at very high risk.

Background Infection prevention and control (IPC) measures in Japan are facilitated by a financial incentive process at the national level, where facilities are categorized into three groups (Tier 1, Tier 2, or no financial incentive). However, its impact on IPC at the facility level using a validated tool has not been measured. Methods A nationwide cross-sectional study was conducted from August 2019 to January 2020 to evaluate the situation of IPC programs in Japan, using the global IPC Assessment Framework (IPCAF) developed by the World Health Organization. Combined with the information on the national financial incentive system, the demographics of facilities and each IPCAF item were descriptively analyzed. IPCAF scores were analyzed according to the facility level of care and the national financial incentive system for IPC facility status, using Dunn-Bonferroni and Mann–Whitney U tests. Results Fifty-nine facilities in Japan responded to the IPCAF survey: 34 private facilities (57.6%) and 25 public facilities (42.4%). Of these, 11 (18.6%), 29 (49.2%), and 19 (32.3%) were primary, secondary, and tertiary care facilities, respectively. According to the national financial incentive system for IPC, 45 (76.3%), 11 (18.6%), and three (5.1%) facilities were categorized as Tier 1, Tier 2, and no financial incentive system, respectively. Based on the IPCAF total score, more than half of the facilities were categorized as “Advanced” (n = 31, 55.3%), followed by “Intermediate” (n = 21, 37.5%). The IPCAF total score increased as the facility level of care increased, while no statistically significant difference was identified between the secondary and tertiary care facilities (p = 0.79). There was a significant difference between Tier 1 and Tier 2 for all core components and total scores. Core components 5 (multimodal strategies for implementation of IPC interventions) and 6 (monitoring/audit of IPC and feedback) were characteristically low in Japan with a median score of 65.0 (interquartile range 40.0–85.0) and 67.5 (interquartile range 52.5–87.5), respectively. Conclusions The national financial incentive system was associated with IPC programs at facility level in Japan. The current financial incentive system does not emphasize the multimodal strategy or cover monitoring/audit, and an additional systematic approach may be required to further promote IPC for more practical healthcare-associated infection prevention.

Background: Increased γ-glutamyl transpeptidase (GGT) levels can deplete plasma glutathione, which in turn impairs immune regulation; however, evidence on GGT levels and post-vaccine immunogenicity is lacking. Objective: To examine the association between GGT and SARS-CoV-2 spike IgG antibodies. Methods: Participants were 1479 medical staff (aged 21 to 75 years) who received a SARS-CoV-2 antibody test after their second vaccine and whose GGT levels were measured before the vaccine rollout. Elevated and highly elevated GGT levels were defined as 51–80 and ≥81 U/L, respectively. Multivariable linear regression was used to calculate the means of SARS-CoV-2 spike IgG. Results: In a basic model, both elevated and highly elevated GGT levels were associated with significantly lower antibody titers. The ratio of mean (95% CI) was 0.83 (0.72–0.97) and 0.69 (0.57–0.84) for elevated and highly elevated GGT levels, respectively. However, these associations were largely attenuated after additional adjustment for potential confounders. An inverse association between GGT levels and antibody titers was found in women [0.70 (0.51–0.97)], normal-weight adults [0.71 (0.51–0.98)], and non-drinkers [0.73 (0.46–1.14)] but not in men, overweight adults, and alcohol drinkers. Conclusions: Circulating GGT concentrations were associated with the humoral immune response after COVID-19 vaccination, but this relationship could be ascribed to confounders such as sex, BMI, and alcohol drinking rather than GGT per se.

To compare the characteristics and clinical course of patients with coronavirus disease (COVID-19) according to the healthcare level of the admitted hospital, to provide an insight into determining the appropriate level of care for each patient.This retrospective, observational study utilized data from the COVID-19 Registry Japan (COVIREGI-JP), the largest Japanese registry of hospitalized patients with COVID-19. Datasets were obtained from reports filed as of May 31, 2022.A total of 59,707 patients (2004 in the primary care group, 41,420 in the secondary care group, and 16,283 in the tertiary care group) from 585 facilities were included in the analysis. Patients with established risk factors for severe disease, such as old age and the presence of comorbidities, were treated at higher care facilities and had poorer initial conditions and in-hospital clinical course, as well as higher mortality. Analysis of the fatality rates for each complication suggested that patients with complications requiring procedures (e.g. pleural effusions, myocardial ischemia, and arrhythmia) may have better survival rates in facilities with specialist availability. The number of deaths and severe COVID-19 cases in this study were notably less than those reported overseas.Our results showed that more difficult COVID-19 cases with poor outcomes were treated at higher care level facilities in Japan. Attending to possible complications may be useful for selecting an appropriate treatment hospital. Healthcare providers need to maintain a broad perspective on the distribution of medical resources.

This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic ARSCoV- 2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], –2.42 [1.42]; P = 0.0712) and 250 mg (–2.81 [1.21]; P = 0.0083) versus placebo (–1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by –1.4 to –1.5 log10 copies/ mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350)., Antimicrobial Agents and Chemotherapy, 66(10), art. no. e0069722; 2022

Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and conditions in AMR policy advocacy. It also aims to identify AMR implementation conditions where AMR national policies are adopted and, to a certain extent, formulated and implemented. This study adopts qualitative research methodology and applies the Grounded Theory Framework to identify thematic findings from interviews conducted in China, Japan, Norway, the United Kingdom (UK), and the United States of America (US). It was identified that AMR policy protagonists are critical to filtering AMR issues and identifying policies “fit to prioritize” and “fit to implement”. They have helped move policy prioritization needles in the UK and the US and engaged in diplomatic efforts in the UK. In these cases, no clientelism was considered. In the US, protagonists who talked to the right decision-makers in the right office at the right time both moved AMR issues from individuals to institutional agenda and from social norms to policy agenda. To conclude, there are three thematic policy conditions that are significant to AMR policy advocacy and implementation: committed personal championship, institutionalization of policies, and social norms facilitate AMR policy advocacy and implementation.

Background Polymyxin E (colistin) is a last-resort antibiotic to treat infections caused by carbapenemase-producing Enterobacteriaceae (CPE). However, reports of CPEs resistant to colistin have been increasing, and the mcr genes are emerging as resistance mechanisms. Among them, plasmid-mediate mcr-9 is known to be associated with colistin resistance, whereas reports on chromosomal mcr-9 and its association with colistin resistance in humans are few. Case presentation We identified Enterobacter asburiae harboring mcr-9 and blaIMP-60 in the pleural fluid of a patient with empyema. The long-read sequencing technique revealed that these genes were located on its chromosome. Despite the lack of exposure to colistin, the organism showed microcolonies in the inhibition circle in the E-test and disk diffusion test. Antibiotic susceptibility testing by broth microdilution confirmed its resistance to colistin. Conclusion Our case report showed that mcr-9 can be present not only on plasmids but also on the chromosome in E. asburiae, and that the presence of mcr-9 on its chromosome may influence its susceptibility to colistin.

We investigated epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergent evacuation from Wuhan, China to Japan under the COVID-19 outbreak in 2020. A total of 12 of 14 returnees (median age [range]: 49.5 years [29-65 years]; 9 men [75%]) were confirmed COVID-19. The proportions of returnees with COVID-19 were 12/566 (2.1%) in the 1-3 flights and 2/263 (0.8%) in the 4-5 flights. Six patients were asymptomatic on admission, while three patients developed symptoms thereafter. None reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients contacted with an individual confirmed or suspected to have COVID-19, respectively. Most patients resided in hotels in the center of Wuhan city, taking taxis and trains to work and supermarkets. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk may have been necessary to prevent infection. In addition, forced social distancing due to lockdown might contribute to the lower infection rates in Flights 4 and 5, compared to Flights 1-3.