上原 由紀

BACKGROUND Fermented foods, such as yogurt, are often considered healthy; however, there have been numerous reported cases of bacteremia associated with their consumption. In this report, we present a case of Bacillus subtilis var. natto (B. subtilis var. natto) bacteremia related to the consumption of natto, a traditional Japanese food made from fermented soybeans. We also conducted a literature review on B. subtilis bacteremia. CASE REPORT We report the case of a 41-year-old woman who presented with fever, had a medical history of congenital liver fibrosis, and experienced recurrent B. subtilis var. natto bacteremia along with acute cholangitis. Although she discontinued eating natto, she developed pyogenic thrombophlebitis due to B. subtilis var. natto. We successfully treated her with meropenem and an anti-coagulant. To investigate the management and prognosis of B. subtilis var. natto bacteremia, we conducted a literature review of B. subtilis intra-abdominal infection. We identified 17 papers describing 30 cases of B. subtilis intra-abdominal infection, 4 cases of which were caused by B. subtilis var. natto; the median age of the patients was 71 years (range, 15-96 years), 14 patients (47%) were female, and 3 patients (10%) died. From our findings, our case was the only one of recurrent B. subtilis var. natto infection. Even after patients discontinue eating natto, they should be carefully monitored. CONCLUSIONS Due to advancements in PCR identification techniques, case reports of infections caused by B. subtilis var. natto are increasing.

We report three cases of Clostridium butyricum bacteremia associated with taking C. butyricum-related probiotics. We performed a literature review and found 11 cases of C. butyricum bacteremia including our cases. Nine cases related to probiotics. We should consider that probiotics may infect clinically unstable patients.

Although infection with the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 is extremely rare in Japan, the uniquely evolved clone ΨUSA300 has been reported in Japan. An outbreak of a distinct USA300 clone was recently reported in an HIV/AIDS referral hospital in Tokyo. The present study investigated the evolutionary origin and genetic diversity of USA300-related clones causing regional outbreaks among people living with HIV (PLWHIV) in Tokyo. MRSA isolates collected from PLWHIV in an HIV/AIDS referral center in Tokyo were subjected to whole-genome sequencing and their genetic features were compared with those of previously described USA300 MRSA genomes. Of the 28 MRSAs isolated in 2016-2019, 23 (82.1%) were identified as USA300, with 22 (95.6%) of the latter identified as ΨUSA300. Although the genomic structure of ΨUSA300 was identical to the structures of reference USA300 strains, one clade (cluster A) was found to have acquired 29 previously identified lineage-specific mutations in a stepwise manner. The estimated divergence dates of ΨUSA300 and Cluster A were 2009 and 2012, respectively. These findings suggested that the ΨUSA300 clone had spread among PLWHIVs in Tokyo in the early 2010s, with stepwise acquisition of lineage-specific nonsynonymous mutations.

Abstract In this multi-center prospective test-negative case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent COVID-19 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared to no vaccination (65% and 76%) and moderate compared to monovalent vaccines administered over half a year before (46% combined).

A 38-year-old female with systemic lupus erythematosus (SLE) initiated belimumab treatment. One month later, she presented with a reddish painful swelling on her right lower leg. She was treated with ceftriaxone and vancomycin. However, novel erythematous papules and indurated nodules appeared on both her lower legs. Skin biopsy revealed microabscess formation with mixed cell granuloma surrounded by inflammatory cell infiltration within the dermis with subcutaneous fat tissue. A large number of acid-fast bacilli were observed with Ziehl-Neelsen staining. DNA sequencing of both the hsp65 and the 16S rRNA sequences showed a 100% match with the corresponding region of Mycobacterium haemophilum. Mycobacterial culture revealed satellite growth enhancement on Middlebrook 7H11 agar plates around a paper strip containing hemin. She was treated with levofloxacin, rifabutin, and ethambutol. Within 13 months, her cutaneous lesions improved markedly without any side effects. The B cell-targeted biologic belimumab, a fully humanized IgG1γ monoclonal antibody that inactivates B lymphocyte stimulator, has been considered to be beneficial for active SLE. However, this therapy could increase the risk for the development of biologic therapy-associated mycobacterial infections, both tuberculosis and nontuberculous mycobacteria infections.

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.

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.

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.

Three isolates of the Enterobacter cloacae complex harboring mcr-9, a member of the colistin resistance mcr gene family encoded on plasmids, were susceptible to colistin, with MICs of 0.125 to 0.5 μg/mL in standard broth microdilution (BMD) tests using cation-adjusted Mueller-Hinton broth (CA-MHB) in accordance with European Committee on Antimicrobial Susceptibility Testing guidelines. In contrast, their MICs for colistin were significantly higher (4 to 128 μg/mL) when BMD tests were performed using brain-heart infusion (BHI) medium, Luria-Bertani (LB) broth, tryptic soy broth (TSB), or CA-MHB supplemented with casein, tryptonen or peptone. Colistin significantly induced mcr-9 expression in a dose-dependent manner when these mcr-9-positive isolates were cultured in BHI or CA-MHB supplemented with peptone/casein. Pretreatment of mcr-9-positive isolates and Escherichia coli DH5α harboring mcr-9 with colistin significantly increased their survival rates against LL-37, a human antimicrobial peptide. Electrospray ionization time-of-flight mass spectrometry analysis showed that a lipid A moiety of lipopolysaccharide was partially modified by phosphoethanolamine in E. coli DH5α harboring mcr-9 when treated with colistin. Of 93 clinical isolates of Enterobacteriaceae, only the mcr-9-positive isolates showed MICs to colistin that were at least 32 times higher in BHI than in CA-MHB. These mcr-9-positive isolates grew on a modified BHI agar, MCR9-JU, containing 3 μg/mL colistin. These results suggest that the BMD method using BHI is useful when performed together with the BMD method using CA-MHB to detect mcr-9-positive isolates and that MCR9-JU agar is useful in screening for Enterobacteriaceae isolates harboring mcr-9 and other colistin-resistant isolates.

A ψUSA300 clone of MRSA, a derivative of USA300, is uniquely found in Japan and has 12-bp deletion on ccrB2 in type IVa staphylococcal cassette chromosome mec element. We hereby present the complete genome of ψUSA300 strain JICS127.

BACKGROUND: The relative burden of COVID-19 has been less severe in Japan. One reason for this may be the uniquely strict restrictions imposed upon bars/restaurants. To assess if this approach was appropriately targeting high-risk individuals, we examined behavioral factors associated with SARS-CoV-2 infection in the community. METHODS: This multicenter case-control study involved individuals receiving SARS-CoV-2 testing in June-August 2021. Behavioral exposures in the past 2 weeks were collected via questionnaire. SARS-CoV-2 PCR-positive individuals were cases, while PCR-negative individuals were controls. RESULTS: The analysis included 778 individuals (266 [34.2%] positives; median age [interquartile range] 33 [27-43] years). Attending three or more social gatherings was associated with SARS-CoV-2 infection (adjusted odds ratio [aOR] 2.00 [95% CI 1.31-3.05]). Attending gatherings with alcohol (aOR 2.29 [1.53-3.42]), at bars/restaurants (aOR 1.55 [1.04-2.30]), outdoors/at parks (aOR 2.87 [1.01-8.13]), at night (aOR 2.07 [1.40-3.04]), five or more people (aOR 1.81 [1.00-3.30]), 2 hours or longer (aOR 1.76 [1.14-2.71]), not wearing a mask during gatherings (aOR 4.18 [2.29-7.64]), and cloth mask use (aOR 1.77 [1.11-2.83]) were associated with infection. Going to karaoke (aOR 2.53 [1.25-5.09]) and to a gym (aOR 1.87 [1.11-3.16]) were also associated with infection. Factors not associated with infection included visiting a cafe with others, ordering takeout, using food delivery services, eating out by oneself, and work/school/travel-related exposures including teleworking. CONCLUSIONS: We identified multiple behavioral factors associated with SARS-CoV-2 infection, many of which were in line with the policy/risk communication implemented in Japan. Rapid assessment of risk factors can inform decision making.

BACKGROUND: Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

We describe a domestic case of retropharyngeal abscess (RPA) in a child caused by a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate that was genetically proven to be the USA300 clone (sequence type [ST]8-SCCmec IVa-Panton-Valentine leukocidin [PVL]). USA300 generally has a PVL gene, an epidemiologic association with severe and recurrent skin and soft tissue infection, and is the leading cause of RPA in the United States. A 1-year-old previously healthy girl visited the emergency department with fever, sore throat, and a difficulty in moving her neck. The patient had no recent medical exposure or history of travel abroad. Enhanced computed tomography revealed a bulky low-density area with ring enhancement in the retropharyngeal and right parapharyngeal spaces. MRSA was isolated from pus obtained from surgical drainage, and antibiotics were continued for a total of 21 days. MRSA was analyzed by whole genome sequencing and compared with representative USA300 isolates. The strain was typed as ST8-t9829-SCCmec IVa with PVL and arginine catabolic mobile element, and its sequence was 99.8% identical to USA300 isolates. The present case supports the possibility that USA300 is potentially spreading in the Japanese community and raises the possibility of USA300 invasive infections without a clear route of infection.

BACKGROUND We aimed to identify the risk factors for Stenotrophomonas maltophilia infection in patients with COVID-19. CASE REPORT Case 1. A 52-year-old COVID-19-positive woman with systemic lupus erythematosus was administered remdesivir (RDV) and methylprednisolone (mPSL) 1000 mg/day for 3 days, and subsequently administered baricitinib and ceftriaxone. Following respiratory deterioration, she was transferred to the Intensive Care Unit (ICU) and the antibiotics were switched to meropenem (MEPM). Blood and sputum cultures were positive for S. maltophilia. Administration of trimethoprim-sulfamethoxazole (TMP-SMX) showed clinical improvement. Case 2. An 80-year-old COVID-19-positive man was treated with RDV, dexamethasone, and baricitinib. Owing to severe hypoxia, he was transferred to the ICU and MEPM was administered. Sputum culture was positive for S. maltophilia. TMP-SMX administration temporarily improved his symptoms; however, he died from COVID-19-associated invasive aspergillosis. Case 3. A 48-year-old COVID-19-positive man who was mechanically intubated was transferred to our hospital and treated with RDV, mPSL, and piperacillin/tazobactam. Sputum culture revealed S. maltophilia; treatment with TMP-SMX improved his respiratory status. Case 4. An 80-year-old COVID-19-positive man was treated with RDV and dexamethasone. Owing to severe hypoxemia, he was transferred to the ICU and the antibiotics were switched to MEPM. Sputum culture revealed S. maltophilia. Administration of TMX-SMX improved his respiratory status. CONCLUSIONS Isolation of S. maltophilia in respiratory specimens of patients with COVID-19 should prompt clinicians to administer treatment for S. maltophilia-associated pneumonia in ICU-admitted patients who have been intubated, have been administered broad-spectrum antibiotics, or have immunocompromised status.

BACKGROUND We report a case of diffuse alveolar hemorrhage (DAH) caused by Legionella pneumophila serogroup (SG) 1 and review the existing literature to identify risk factors and determine the prognosis of patients with Legionella pneumonia-associated DAH. CASE REPORT A 44-year-old woman was admitted to our hospital following the presentation of dyspnea for a few days. Chest computed tomography (CT) findings revealed "crazy-paving" pattern in the right upper lobe implicating DAH and consolidation in the lower lobe. Analysis of the bronchoalveolar lavage (BAL) fluid revealed DAH, with further analyses identifying L. pneumophila SG 1 as the causative agent. The patient was successfully treated with levofloxacin and a red blood cell transfusion and discharged on the 32nd day of hospitalization. A literature review of 6 reported cases (including our case) of Legionella pneumonia-associated DAH revealed that the median age of patients with DAH was 59 years (range, 44-75 years), involving female patients in 4 cases (67%) and the use of immunosuppressive drugs in 2 cases (33%). Three cases were BAL Legionella polymerase chain reaction (PCR)-positive and 4 cases were diagnosed using a urinary Legionella antigen test (one case was simultaneously PCR-positive). These infections were caused by L. pneumophila SG 1 in three cases and SG 3 in one case. Mechanical ventilation was used in 5 cases (83%) and one patient had an unfavorable prognosis. Steroids for DAH were used in 5 cases (83%), and 2 cases responded to this treatment. CONCLUSIONS Our case highlights that clinicians should be aware of Legionella spp. as a cause of DAH in an immunocompetent host with "crazy-paving" pattern on chest CT, and perform a urinary antigen test and BAL PCR for diagnosis.

Faropenem (FRPM) is active against extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, but evidence for its efficacy is lacking. This study determined the correlation between the susceptibility by disk diffusion method and the MIC of FRPM for third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, and the effectiveness of FRPM for the treatment of urinary tract infection (UTI) caused by these two bacteria in a retrospective cohort analysis. Of the 48 third-generation cephalosporin-resistant clinical isolates tested, 44 isolates produced ESBL, and 8 isolates produced AmpC, including 4 isolates produced both ESBL and AmpC. Thirty-seven isolates had an FRPM MIC of ≤1 mg/L, and seven had an FRPM MIC of 2 mg/L. An FRPM MIC of >2 mg/L was observed with four isolates. In a retrospective cohort analysis, 63 patients with UTI treated with FRPM were identified. All isolates of ESBL-producing E. coli (n = 54) and K. pneumoniae (n = 9) treated with FRPM showed disk diffusion zone diameters larger than 16.0 mm (estimated MIC, 2.2 mg/L). All patients completed the scheduled treatment courses with FRPM, but 28- and 90-day relapses happened in 10 patients (16%) and 16 patients (25%), respectively. No significant risk factors for the 28- and 90-day relapses were found. FRPM can be used according to disk diffusion susceptibility testing in UTI. Further investigations are necessary to assess the clinical breakpoint of FRPM for ESBL-producing Enterobacterales and the candidates most likely to benefit from using FRPM.

BACKGROUND: Effectiveness of restricting healthcare providers (HCPs) from working based on the coronavirus disease 2019 (COVID-19)-like symptoms should be evaluated. METHODS: A total of 495 HCPs in a tertiary care hospital in Tokyo, Japan, participated in this study between June and July in 2020. Analysis of serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody to identify infected HCPs, questionnaire surveys, and medical record reviews were conducted to evaluate the appropriateness of symptom-based work restriction for 10 days. RESULTS: Five participants (1.0%) were identified as infected. Forty-six participants (9.3%) experienced work restriction and all 5 infected participants (10.8%) restricted working, even though the real-time reverse transcription-polymerase chain reaction was positive only in 4 participants (80.0%). There were no unexpectedly infected participants among those who did not experience work restriction. However, only 46 of 110 HCPs with COVID-19-like symptoms (41.8%) restricted themselves from working. DISCUSSION: Symptom-based work restriction strategy successfully prevented infected HCPs to work, but showed low specificity to identify truly infected HCPs, and their low adherence to the strategy was revealed. CONCLUSIONS: HCPs with COVID-19-like symptoms should restrict working as the first step of infection prevention, but the strategy to identify truly infected HCPs is necessary.

BACKGROUND: Treatment of patients with penicillin-resistant S. pneumoniae (PRSP) is complicated because of the relatively poor blood-brain barrier penetration of effective antimicrobials. Our case: A previously healthy 70-year-old woman, a traveler from China to Japan, was admitted to our hospital with fever and loss of consciousness. She has no history of pneumococcal vaccination. She was diagnosed with bacterial meningitis due to penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae. The patient was successfully treated with a combination therapy of vancomycin (VCM) and levofloxacin (LVFX) and recovered without any neurological sequelae. As the treatment of penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae meningitis remains unclear, we conducted a review of the reported cases of meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae. METHOD: We performed a search using the keywords "penicillin-resistant Streptococcus pneumoniae," "meningitis," and "pneumococcal meningitis". We searched the electronic databases PubMed, Embase, and Ichushi from their inception to March 2020. Subsequently, two authors independently reviewed the resulting database records, retrieved full texts for eligibility assessment, and extracted data from these cases. RESULT: We identified 18 papers describing thirty-five cases of penicillin- and cephalosporin-resistant S. pneumoniae meningitis including our case. The patient's characteristics were; median age: 50 years, men:50%, 85% of cases received combination regimens of antibiotics: Ceftroriaxone (CTRX) plus VCM (20 cases), CTRX plus VCM plus rifampicin (RFP) (two cases), CTRX plus linezolid (one case), fluoroquinolones (two cases), carbapenems (six cases), Thirty-five percent received steroids. Twenty-four percent of patients died. Twenty-six percent of patients complicated neurological sequalae. CONCLUSION: Combination therapy including VCM plus LVFX could be a treatment option.

Female participants had a higher incidence of headache, nausea, myalgia, arthralgia, redness, pruritus, and inoculation site redness and pruritus (p 0.05). Low grade fever, headache, malaise, myalgia, and inoculation site induration and heat were associated with age group (p 0.05).

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2-7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10-17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials.

The risk factors for eosinophilic pneumonia (EP) remain unclear. We investigate the characteristics of patients with daptomycin (DAP)-induced EP and conducted a retrospective observational study. A total of 450 patients aged ≥ 18 years who received DAP (25 DAP with EP, 425 DAP without EP) were included. The median duration from the first DAP administration to EP onset was 18.0 days. Definite, probable, and possible DAP-induced EP were diagnosed in 0, 9, and 16 patients, respectively. The median age (DAP with EP, 72.0 years; DAP without EP, 64.0 years), DAP dosage/body weight (BW) (9.00 vs. 7.50 mg/kg), blood eosinophil count (cells/μL) (419 vs. 96), and the percentage of hemodialyzed patients (40.0% vs. 13.4%) were significantly higher in patients with EP than in patients without EP in the univariate analysis. In separate multivariate logistic regression analyses, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.00-1.05), DAP dosage/BW (OR, 1.61; 95% CI, 1.25-2.07), and hemodialysis (OR, 4.42; 95% CI, 1.86-10.5) were significantly associated with DAP-induced EP. Clinicians may need to consider the potential factors associated with EP, especially in older patients, patients on hemodialysis, or patients who receive > 9.00 mg/kg of DAP.

Staphylococcal cassette chromosome mec (SCCmec) typing was established in the 2000s and has been employed as a tool for the molecular epidemiology of methicillin-resistant Staphylococcus aureus, as well as the evolution investigation of Staphylococcus species. Molecular cloning and the conventional sequencing of SCCmec have been adopted to verify the presence and structure of a novel SCCmec type, while convenient PCR-based SCCmec identification methods have been used in practical settings for many years. In addition, whole-genome sequencing has been widely used, and various SCCmec and similar structures have been recently identified in various species. The current status of the SCCmec types, SCCmec subtypes, rules for nomenclature, and multiple methods for identifying SCCmec types and subtypes were summarized in this review, according to the perspective of the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements.

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.

BACKGROUND: The worldwide spread of carbapenemase-producing Enterobacteriaceae (CPE) has reduced the clinical utility of carbapenems. Plasmids often play an important role in the spread of genes encoding drug-resistance factors, especially in the horizontal transfer of these genes among species of Enterobacteriaceae. This study describes a patient infected with three species of CPE carrying an identical transferrable IncL/M plasmid. METHODS: Clinical isolates of CPE were collected at St. Luke's International Hospital, Tokyo, Japan, from 2015 to 2019. Three species of CPE isolates, Enterobacter cloacae, Klebsiella aerogenes and Serratia marcescens, were isolated from a patient who developed severe gallstone pancreatitis associated with bloodstream infection, with all three isolates producing IMP-1 metallo-β-lactamase. The complete sequences of the plasmids of the three isolates were determined by both MiSeq and MinION. The medical chart of this patient was retrospectively reviewed conducted to obtain relevant clinical information. RESULTS: The three CPE species carried an IncL/M plasmid, pSL264, which was 81,133 bp in size and harbored blaIMP-1. The genetic environment surrounding blaIMP-1 consisted of int1-blaIMP-1-aac(6')-IIc-qacL-qacEdelta1-sul1-istB-IS21. Conjugation experiments showed that S. marcescens could transmit the plasmid to E. cloacae and K. aerogenes. In contrast, pSL264 could not transfer from E. cloacae or K. aerogenes to S. marcescens. CONCLUSION: The IncL/M plasmid pSL264 harboring blaIMP-1 was able to transfer among different species of Enterobacteriaceae in a patient receiving long-term antimicrobial treatment. The worldwide emergence and spread of IncL/M plasmids harboring carbapenemase-encoding genes among species of Enterobacteriaceae is becoming a serious public health hazard.

BACKGROUND: Infections caused by Enterococcus hirae are common in animals, with instances of transmission to humans being rare. Further, few cases have been reported in humans because of the difficulty in identifying the bacteria. Herein, we report a case of pyelonephritis caused by E. hirae bacteremia and conduct a literature review on E. hirae bacteremia. CASE PRESENTATION: A 57-year-old male patient with alcoholic cirrhosis and neurogenic bladder presented with fever and chills that had persisted for 3 days. Physical examination revealed tenderness of the right costovertebral angle. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) of the patient's blood and urine samples revealed the presence of E. hirae, and pyelonephritis was diagnosed. The patient was treated successfully with intravenous ampicillin followed by oral linezolid for a total of three weeks. CONCLUSION: The literature review we conducted revealed that E. hirae bacteremia is frequently reported in urinary tract infections, biliary tract infections, and infective endocarditis and is more likely to occur in patients with diabetes, liver cirrhosis, and chronic kidney disease. However, mortality is not common because of the high antimicrobial susceptibility of E. hirae. With the advancements in MALDI-TOF MS, the number of reports of E. hirae infections has also increased, and clinicians need to consider E. hirae as a possible causative pathogen of urinary tract infections in patients with known risk factors.

BACKGROUND: Entamoeba histolytica (E. histolytica) is rarely identified as a cause of amebic pericarditis. We report a case of amebic pericarditis complicated by cardiac tamponade, in which the diagnosis was missed initially and was made retrospectively by polymerase chain reaction (PCR) testing of a stored sample of pericardial fluid. Furthermore, we performed a systematic review of the literature on amebic pericarditis. CASE PRESENTATION: A 71-year-old Japanese man who had a history of sexual intercourse with several commercial sex workers 4 months previously, presented to our hospital with left chest pain and cough. He was admitted on suspicion of pericarditis. On hospital day 7, he developed cardiac tamponade requiring urgent pericardiocentesis. The patient's symptoms temporarily improved, but 1 month later, he returned with fever and abdominal pain, and multiple liver lesions were found in the right lobe. Polymerase chain reaction of the aspiration fluid of the liver lesion and pericardial and pleural fluid stored from the previous hospitalization were all positive for E. histolytica. Together with the positive serum antibody for E. histolytica, a diagnosis of amebic pericarditis was made. Notably, the diagnosis was missed initially and was made retrospectively by performing PCR testing. The patient improved with metronidazole 750 mg thrice daily for 14 days, followed by paromomycin 500 mg thrice daily for 10 days. CONCLUSIONS: This case suggests that, although only 122 cases of amebic pericarditis have been reported, clinicians should be aware of E. histolytica as a potential causative pathogen. The polymerase chain reaction method was used to detect E. histolytica in the pericardial effusion and was found to be useful for the diagnosis of amebic pericarditis in addition to the positive results for the serum antibody testing for E. histolytica. Because of the high mortality associated with delayed treatment, prompt diagnosis should be made.

OBJECTIVES: Coronavirus disease (COVID-19) blindness, that is, the excessive consideration of the disease in diagnosis, has reportedly led to delayed diagnosis of some diseases. We compared several clinical measures between patients admitted for bacteremia during the two months of the COVID-19 pandemic and those admitted during the same period in 2019. We hypothesized that the pandemic has led to delayed treatment of bacteremia. METHODS: This retrospective observational study compared several measures undertaken for patients who visited the emergency unit in two hospitals between March 1 and May 31, 2020, during the COVID-19 pandemic and whose blood cultures tested positive for bacteremia with those for corresponding patients treated during the same period in 2019. The primary measure was time from consultation to blood culture/antimicrobials. RESULTS: We included 29 eligible patients from 2020 and 26 from 2019. In 2020, the time from consultation to antimicrobial administration was significantly longer than in 2019 (mean [range], 222 [145-309] min vs. 139 [102-179] min, p=0.002). The frequency of chest computed tomography (CT) was significantly higher in 2020 (96.6 vs. 73.1%, p=0.021). Significant differences were not observed in the time to blood culture or chest CT preceding the blood culture between the two periods. CONCLUSIONS: Our findings suggested that due to the COVID-19 epidemic/pandemic, focusing on the exclusion of its infection using CT scans leads to an overall delay in the diagnosis and treatment of bacteremia. Medical providers must be aware of COVID-19 blindness and evaluate patients objectively based on rational criteria and take appropriate action.

BACKGROUND: Despite multi-professional collaboration via consultation being increasingly important given the variety of disease diagnoses and treatment, the key elements as consultants remain unclear. The study aimed to identify the skills and attitudes that are important for consultants from the residents' perspective so that they can be targeted as priority goals in subsequent educational interventions. METHODS: We conducted our research in two phases: a preliminary survey (May 1 to 14, 2020) and a main survey (June 1 to 14, 2020). As a preliminary survey, first-year postgraduate residents at St. Luke's International Hospital in Tokyo, Japan, were first asked an open-ended question about the types of skills and attitudes that are important for consultants. After eliminating duplicate answers, there were 19 skills and attitudes in total. In the main survey with residents who completed their residency training at our institute, from 2014 to 2018 and current residents (2019-2020), we first asked them about their demographic characteristics (gender, years of postgraduate education, and type of specialty). Then, they answered how important each skill and attitude are for consultants. All 19 items were scored on a seven-point Likert scale that ranged from 0 (completely disagree) to 6 (totally agree). Cronbach's alpha confirmed the internal consistency of the questionnaire items. Principal component analysis and exploratory factor analysis were performed. RESULTS: The survey included 107 individuals (61.1 %, 175 potential participants). The median postgraduate years of education was four (interquartile range: 2-5), and 64.5 % were men (n = 69). Seven key elements for consultants were identified and termed Willing CONSULT. These included (1) willingness (willingness to accept consultation requests), (2) contact (easy access to consultants), (3) needs (consideration of consulters' needs), (4) suggestions and support (providing clear recommendations and suggestions, following up on the patients, and supporting the consulters continuously), (5) urgency (considering the situation's urgency and responding appropriately), (6) learning opportunities (providing teaching points), and (7) text (writing medical records). CONCLUSIONS: We propose Willing CONSULT, which are important skills and attitudes for consultants.

＜文献概要＞日本の感染症診療のバイブルともいえる『レジデントのための感染症診療マニュアル』は発行から20年ほど経ち,初版で学んだ自分の研修医時代とはかなり違う常識が広がってきているように感じます.そこで,著者である青木先生,青木先生のもとで学ばれ日本感染症教育研究会(IDATEN)の代表世話人を務めてられている上原先生のお2人に,どういった変化を感じておられるのか,また,感染症の教育がどう変化し,今後さらに改善・成長の余地があるのかを伺えればと思います.

To trace the linkage between Japanese healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) strains in the early 1980s and the 2000s onward, we performed molecular characterizations using mainly whole-genome sequencing. Among the 194 S. aureus strains isolated, 20 mecA-positive MRSA (10.3%), 8 mecA-negative MRSA (4.1%) and 3 mecA-positive methicillin-susceptible S. aureus (MSSA) (1.5%) strains were identified. The most frequent sequence type (ST) was ST30 (n = 11), followed by ST5 (n = 8), ST81 (n = 4), and ST247 (n = 3). Rates of staphylococcal cassette chromosome mec (SCCmec) types I, II, and IV composed 65.2%, 13.0%, and 17.4% of isolates, respectively. Notably, 73.3% of SCCmec type I strains were susceptible to imipenem unlike SCCmec type II strains (0%). ST30-SCCmec I (n = 7) and ST5-SCCmec I (n = 5) predominated, whereas only two strains exhibited imipenem-resistance and were tst-positive ST5-SCCmec II, which is the current Japanese HA-MRSA genotype. All ST30 strains shared the common ancestor strain 55/2053, which caused the global pandemic of Panton-Valentine leukocidin-positive MSSA in Europe and the United States in the 1950s. Conspicuously more heterogeneous, the population of HA-MRSA clones observed in the 1980s, including the ST30-SCCmec I clone, has shifted to the current homogeneous population of imipenem-resistant ST5-SCCmec II clones, probably due to the introduction of new antimicrobials.

BACKGROUND: USA300 produces Panton-Valentin leucocidin (PVL) and is known as a predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in the United States, but it was extremely rare in Japan. We report here an outbreak of USA300 in people with HIV (PWH) in Tokyo, Japan. METHODS: We analyzed the cases of PVL-MRSA infection between 2010 and 2020 and screened for nasal colonization of PVL-MRSA in PWH who visited an HIV/AIDS referral hospital from December 2019 to March 2020. Whole-genome sequencing-based single nucleotide polymorphism (SNP) analysis was performed on these isolates. RESULTS: During the study period, a total of 21 PVL-MRSA infections in 14 patients were identified after 2014. The carriage prevalence was 4.3% (12/277) and PVL-MRSA carriers were more likely to have sexually transmitted infections (STIs) within a year compared with patients who had neither a history of PVL-MRSA infection nor colonization (33.3% [4/12] vs 10.1% [26/258]; P = .03). SNP analysis showed that all 26 isolates were ST8-SCCmecIVa-USA300. Twenty-four isolates were closely related (≤100 SNP differences) and had the nonsynonymous SNPs associated with carbohydrate metabolism and antimicrobial tolerance. CONCLUSIONS: An outbreak of USA300 has been occurring among PWH in Tokyo and a history of STI was a risk of colonization.

Background: Staphylococcus aureus (SA) is the most common causative microorganism in native vertebral osteomyelitis (NVO). Few studies have compared the clinical features of NVO due to SA (SA-NVO) and NVO due to other organisms (NSA-NVO). This study was conducted to validate a predictive score for SA-NVO to facilitate NVO treatment without broad-spectrum antimicrobial agents. Methods: This retrospective study compared the clinical features of patients with SA-NVO and NSA-NVO who were diagnosed from 2004 to 2019. Univariate associations were assessed using χ 2, Fisher's exact, or Mann-Whitney U test. Multivariable analysis was conducted using logistic regression. The optimal age cutoff point was determined by classification and regression tree analysis. Results: Among 155 NVO patients, 98 (63.2%) had a microbiologically confirmed diagnosis: 40 (25.8%) with SA-NVO and 58 (37.4%) with NSA-NVO. Six predictors, either independently associated with SA-NVO or clinically relevant, were used to develop the STAPH prediction score: atopic dermatitis (Skin) (3 points); recent Trauma (2 points); Age < 67 years (1 point); Abscess (1 point); central venous Port catheter (2 points); and History of puncture (2 points). In a receiver operating characteristic analysis, the area under the curve was 0.84 (95% confidence interval, 0.76-0.91). The best cutoff point was 3. A score ≥3 had a sensitivity, specificity, positive predictive value, and negative predictive value of 58%, 84%, 84%, and 73%, respectively. Conclusions: The STAPH score has relatively high specificity for use by clinicians to predict SA as the causative microorganism in patients with NVO until results of a confirmatory culture are available.

A 69-year-old man was brought to our hospital by ambulance with a fever. The translucent pink color of the serum sample suggested severe hemolysis. His blood pressure dropped rapidly, and he later suffered a cardiopulmonary arrest and died approximately 30 h after arriving at our hospital. The day after the patient's death, Clostridium perfringens was detected in the blood culture taken at the time of hospital admission. When serum sample shows translucent pink to red color and bacilli from bacteria is identified in peripheral blood smear, Clostridium perfringens should be considered and appropriate medical treatment should be initiated immediately.

Penicillin-resistant viridans group streptococci (VGS) infections are an emerging issue in infectious diseases. Here, we present a case of mitral valve infective endocarditis caused by highly penicillin-resistant VGS (minimum inhibitory concentration >4 μg/mL), which was successfully treated with daptomycin. Although the clinical efficacy of daptomycin has not been established, it can be an alternative for the treatment of highly resistant VGS endocarditis.

OBJECTIVES: To determine the prevalence of burnout according to job category after the first wave of COVID-19 in Japan and to explore its association with certain factors. METHODS: An online cross-sectional survey of health care workers (HCWs) from June 15 to July 6, 2020, was conducted at a tertiary hospital in Tokyo, Japan. Demographic characteristics, results of the Japanese version of the Maslach Burnout Inventory-General Survey, types of anxiety and stress, changes in life and work after the peak of the pandemic, and types of support aimed at reducing the physical or mental burden, were determined. RESULTS: Of 672 HCWs, 149 (22.6%) met the overall burnout criteria. Burnout was more prevalent in women (OR, 3.11; 95% CI, 1.45-6.67, P = .003), anxiety due to unfamiliarity with personal protective equipment (PPE) (OR, 1.98; 95% CI, 1.20-3.27, P = .007), and decreased sleep duration (OR, 1.96; 95% CI, 1.20-3.20, P = .008). Conversely, participants who felt that the delivery of COVID-19-related information (OR, .608; 95% CI, .371-.996, P = .048) and PPE education opportunities (OR, .484; 95% CI, .236-.993, P = .048) and messages of encouragement at the workplace (OR, .584; 95% CI, .352-.969; p = .037) was helpful experienced less burnout. CONCLUSIONS: There is a need to focus on the above factors to maintain the mental health of HCWs. The delivery of COVID-19-related information and educational interventions for PPE and messages of encouragement at the workplace may be needed to reduce the mental burden.

BACKGROUND: Testicular infarction is a known serious complication associated with epididymitis. It is known to be idiopathic in 70% of cases but the frequency, risk factors, and management are yet to be elucidated. This paper aims to report a case of testicular infarction secondary to pyogenic epididymoorchitis caused by Pseudomonas aeruginosa. CASE PRESENTATION: A 64-year-old male with a past medical history of benign prostate hypertrophy using intermittent self-catheterization and a recent history of culture-negative pyogenic epididymoorchitis treated with oral cefpodoxime was admitted to our hospital due to a 4-week history of fever, right scrotal pain, and swelling. Scrotal ultrasonography showed a hypoechoic testis without testicular torsion. He was diagnosed with testicular infarction and a scrotal abscess due to Pseudomonas aeruginosa, and was treated with cefepime along with transcutaneous drainage. Despite the antimicrobial treatment, he experienced testicular loss with necrotic tissue. Because little is known about the risk factors, clinical characteristics, management, and prognosis of testicular infarction secondary to epididymitis, we performed a systematic review of the literature. CONCLUSION: This is a case of testicular necrosis during the treatment of epididymitis with negative urine culture and detection of Pseudomonas aeruginosa in tissue culture. Clinicians should perform frequent blood flow evaluation to the testis for early urologic intervention.

A 43-year-old man was brought to our hospital with fever. The initial diagnosis was bacterial pneumonia, and ampicillin/sulbactam was administered. However, defervescence was not achieved, and relative bradycardia was observed. Detailed history-taking revealed that the patient had been involved in caring for a wild pigeon before hospitalization. We changed the antimicrobial therapy to minocycline and the patient' s condition improved. Chlamydophila psittaci antibody was subsequently found to be increased four-fold, and psittacosis was diagnosed. This case acts a reminder to clinicians of the importance of both the history of exposure to any birds and vital signs, including relative bradycardia.

当院における院内抗菌薬適正使用チーム(AST)の活動を紹介し、これまでの実績を報告した。適正な薬剤、至適投与時期、至適用量、至適投与期間といった「4R」コンセプトを掲げて薬剤処方の最適化を目指してきた。適正な薬剤:2018年1月、カルバペネムの投与前における血液培養の実施率を高め、5月からその結果を医師にフィードバックした。至適投与時期:2016年、医師と看護師への指導と合わせてバンコマイシンのTDMを実施し、2018年よりAST担当薬剤師のフルタイム勤務体制を導入した。至適用量:セフメタゾールの適正用量について以前のデータとともに医師にフィードバックし、2017年8月に処方オーダリングシステムに改良を加えた。至適投与期間:カルバペネム長期投与中の患者に対してホットラインによる介入を開始し、2016年にチェック回数を10日ごと、さらに2017年には1週ごとに変更した。以上のASTによる介入の結果、血液培養実施率は80%超に高まり、バンコマイシンのTDMはほぼ全例をカバーできるようになった。また、セフメタゾールの用量の適正化が得られ、カルバペネム投与患者に対するチェック回数の増加が認められた。