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Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.

Background. The global point prevalence survey (Global-PPS) is the standard for the surveillance of prescribed antimicrobials among inpatients and provides data for the development of hospital antimicrobial stewardship programs. Aim. To evaluate the prevalence and quality of antimicrobial prescriptions using the universally standardized Global-PPS protocol in a non-acute care hospital in Saitama Prefecture, Japan. Methods. Antimicrobial prescriptions for inpatients, staying at the hospital overnight, were surveyed on three separate week days in November 2018, January 2019, and May 2019. Information on the prescribed antimicrobials on the survey target day was obtained from the in-hospital pharmacy. Survey data were collected by physicians, based on the extracted information. Patient information was anonymized and entered in the Global-PPS Web application by physicians. We report the antimicrobial use prevalence, the indication for prescription, diagnosis, the most prescribed antimicrobials, and a set of quality indicators related to antimicrobial prescribing. Results. In total, 6.7% of the surveyed inpatients (120/1796) were prescribed antimicrobials on the survey day. Sulfamethoxazole/trimethoprim was the most commonly prescribed, with 20.0% of systemic antibiotic prescriptions (ATC J01). Of all antibiotics for systemic use, up to 58.4% were Watch antibiotics, as defined by the World Health Organization AWaRe classification. The most prescribed group of systemic antibiotics was non-penicillin beta-lactam antibiotics (34.4%), followed by penicillin antibiotics in combination with beta-lactamase inhibitors (25.6%), and sulfonamides with trimethoprim (20.8%). Healthcare-associated infections and medical prophylaxis were the most common indications reported in 69.3% and 26.3% of prescriptions, respectively. The most common diagnosis for systemic antibiotic prescriptions was pneumonia (49.6%). Reasons for antimicrobial prescriptions were indicated in the medical records for 67.1% of prescriptions, and the stop/review date was documented to be 50.3%. Compliance with local guidelines reached 66.7%. Conclusions. This study highlights important challenges related to antimicrobial prescription in a highly specific, non-acute care patient population.

BackgroundBoth physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. We aimed to clarify the status of anti-influenza drug use by analyzing real-world data.MethodsThis retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, their age and sex distribution, drug costs, and regional disparities for the period 2014-2020.ResultsFor 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age. Male were more likely than female to be prescribed anti-influenza drugs for inpatient.ConclusionsBased on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.

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.

Background Spread of vancomycin-resistant Enterococcus (VRE) is a global concern as a significant cause of healthcare-associated infections. A series of VRE faecium (VREf) outbreaks caused by clonal propagation due to interhospital transmission occurred in six general hospitals in Aomori prefecture, Japan. Methods The number of patients with VREf was obtained from thirty seven hospitals participating in the local network of Aomori prefecture. Thirteen hospitals performed active screening tests for VRE. Whole genome sequencing analysis was performed. Results The total number of cases with VREf amounted to 500 in fourteen hospitals in Aomori from Jan 2018 to April 2021. It took more than three years for the frequency of detection of VRE to return to pre-outbreak levels. The duration and size of outbreaks differed between hospitals according to the countermeasures available at each hospital. Whole genome sequencing analysis indicated vanA-type VREf ST1421 for most samples from six hospitals. Conclusions This was the first multi-jurisdictional outbreak of VREf sequence type 1421 in Japan. In addition to strict infection control measures, continuous monitoring of VRE detection in local medical regions and smooth and immediate communication among hospitals are required to prevent VREf outbreaks.

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

Tracheobronchial aspergillosis is a rare but lethal disease with characteristic findings of tracheal plaques and ulcers. It requires appropriate airway management for possible tracheal obstruction with the black mucus plug.

Background Shortages of antimicrobials lead to treatment failures, increase medical costs, and accelerate the development of antimicrobial resistance. We evaluated the effects of the serious cefazolin shortage in 2019 in Japan on the sales, costs, and appropriate use of other antimicrobials. Methods We evaluated monthly defined daily doses/1000 inhabitants/day (DID) values of antimicrobial sales from January 2016 to December 2019 using wholesaler’s sales databases. Using 2016–2018 sales data, we generated a prediction model of DID in 2019 under the assumption that the cefazolin shortage did not occur. We then compared the predicted DID and actual DID. Cefazolin, government-recommended alternatives, and government-not-recommended broad-spectrum alternatives were assessed. Antimicrobial groups according to the AWaRe classification were also assessed to evaluate the effect on appropriate antimicrobial use. In addition, we evaluated changes in costs between 9 months before and after the cefazolin shortage. Results DID values of total antimicrobials increased sharply 1 month before the decrease in cefazolin. Actual DIDs were higher than predicted DIDs for ceftriaxone, flomoxef, clindamycin, cefotiam, piperacillin/tazobactam, and meropenem. Actual DID values were higher than the predicted DID values in the Watch group. The costs of antimicrobials between pre- and post- cefazolin shortage were unchanged. Conclusion The cefazolin shortage brought confusion to the antimicrobial market and led to a setback in the appropriate use of antimicrobials. Early recognition and structures for prompt reactions to antimicrobial shortages are needed. Moreover, development of a system to secure the supply of essential antimicrobials is required.

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Background In 2019, the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases reported nationwide, cross-sectional questionnaire survey data investigating the clinical status of clinic doctors' attitudes to antimicrobial stewardship. This study aimed to identify factors determining clinic doctors’ attitudes concerning antimicrobial prescription for patients with a common cold or bronchitis. Methods In February 2018, 1500 randomly selected community-based medical clinics in Japan were sent a questionnaire. Primary and secondary endpoints were clinic doctors’ attitudes concerning antimicrobial prescription, and antimicrobial medication types prescribed for patients with a common cold or bronchitis, respectively. We used multivariable linear regression analysis to identify factors associated with primary and secondary outcomes. Results We analyzed 269 of 274 responses (response rate, 18.3%). Linear regression analysis was used to identify determinants of proactive attitudes to antimicrobial prescription, including whether clinic doctors encountering patients with upper respiratory symptoms and no underlying illnesses, and diagnosed with a common cold would prescribe antimicrobial medication (β = 0.283, t = 4.279, p = 0.000); whether clinic doctors frequently experienced requests from patients (or their families) with a common cold to prescribe antimicrobial medication (β = 0.389, t = 6.133, p = 0.000), and; clinic doctors' awareness of antimicrobial stewardship in the past year (β = −0.157, t = −2.456, p = 0.015). Determinants of proactive attitudes to prescribing broader-spectrum antimicrobials for patients with a common cold included clinic doctors' attitudes concerning antimicrobial prescription (β = 0.165, t = 2.622, p = 0.009), whether the respondent was a pediatrician (β = −0.288, t = −4.583, p = 0.000), and clinic doctors’ attitudes to antimicrobial prescription (β = 0.262, t = 4.075, p = 0.000) for patients with bronchitis. Conclusion This study identified factors among clinic doctors that determined their attitudes to antimicrobial prescription concerning patients with a common cold or bronchitis. Identification and targeting of clinic doctors who unnecessarily prescribe antimicrobial medication is urgently required to promote antimicrobial stewardship in an outpatient setting.

During a COVID-19 outbreak on the Diamond Princess cruise ship we sampled environmental surfaces after passengers and crew vacated cabins. SARS-CoV-2 RNA was detected in 58 of 601 samples (10%) from case cabins 1–17 days after cabins were vacated but not from noncase cabins. There was no difference in detection proportion between cabins of symptomatic (15%, 28/189; cycle quantification [Cq], 29.79–38.86) and asymptomatic cases (21%, 28/131; Cq, 26.21–38.99). No SARS-CoV-2 virus was isolated from any of the samples. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients may be similar and surfaces could be involved in transmission.

SummaryBackgroundA COVID-19 outbreak occurred in a cruise ship with 3711 passengers and crew in 2020. This study is to test the hypothesis that environmental surfaces played important roles in transmission for SARS-CoV-2 during this outbreak.MethodsWe sampled environmental surfaces including air from common areas in the cruise ship and cabins in which confirmed COVID-19 cases and non-cases had stayed after they left the cabins. We tested the samples for SARS-CoV-2 by rt-PCR and conducted viral isolation.FindingsOf 601 samples tested, SARS-CoV-2 RNA was detected from 58 samples (10%) from case-cabins from which they left 1-17 days before sampling, but not from non-case-cabins. Except for one sample from an air hood in a corridor, SARS-CoV-2 RNA was not detected from samples in common areas. SARS-CoV-2 RNA was not detected from all 14 air samples. RNA was most often detected on the floor around toilet in the bathroom (39%, 13/33, cycle quantification (Cq): 26.21-37.62) and bed pillow (34%, 11/32, Cq: 34.61-38.99). There was no difference in the detection proportion between cabins for symptomatic (15%, 28/189, Cq: 29.79-38.86) and asymptomatic cases (21%, 28/131, Cq: 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples.InterpretationThe environment around the COVID-19 cases was extensively contaminated from SARS-CoV-2 during COVID-19 outbreak in the cruise ship. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients seems to be similar and the environmental surface could involve viral transmission through direct contact.

Background To reduce inappropriate antibiotic use, public health campaigns often provide fear-based information about antimicrobial resistance (AMR). Meta-analyses have found that fear-based campaigns in other contexts are likely to be ineffective unless respondents feel confident they can carry out the recommended behaviour (‘self-efficacy’). This study aimed to test the likely impact of fear-based messages, with and without empowering self-efficacy elements, on patient consultations/antibiotic requests for influenza-like illnesses, using a randomised design. Methods We hypothesised that fear-based messages containing empowering information about self-management without antibiotics would be more effective than fear alone, particularly in a pre-specified subgroup with low AMR awareness. Four thousand respondents from an online panel, representative of UK adults, were randomised to receive three different messages about antibiotic use and AMR, designed to induce fear about AMR to varying degrees. Two messages (one ‘strong-fear’, one ‘mild-fear’) also contained empowering information regarding influenza-like symptoms being easily self-managed without antibiotics. The main outcome measures were self-reported effect of information on likelihood of visiting a doctor and requesting antibiotics, for influenza-like illness, analysed separately according to whether or not the AMR information was ‘very/somewhat new’ to respondents, pre-specified based on a previous (non-randomised) survey. Results The ‘fear-only’ message was ‘very/somewhat new’ to 285/1000 (28.5%) respondents, ‘mild-fear-plus-empowerment’ to 336/1500 (22.4%), and ‘strong-fear-plus-empowerment’ to 388/1500 (25.9%) (p = 0.002). Of those for whom the respective information was ‘very/somewhat new’, only those given the ‘strong-fear-plus-empowerment’ message said they would be less likely to request antibiotics if they visited a doctor for an influenza-like illness (p

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

Background Urinary tract infections (UTI) are common and can have severe consequences. However, there are few recent large-scale studies about them. We aimed to determine the incidence of hospitalization for UTI and to elucidate patient characteristics, clinical practice, and clinical outcomes by drawing on a Japanese nationwide database. Methods This was a retrospective observational study using a national database that covers half the acute care inpatients in Japan. Patients aged ≥ 15 years who were hospitalized for UTI were eligible. We did not include patients with lower UTI such as cystitis. We investigated the annual number of patients hospitalized in Japan, those patients’ characteristics, and risk factors for in-hospital mortality. Results We identified 232,396 eligible patients from 31 million records of discharge between April 2010 and March 2015. The average age was 73.5 years and 64.9% of patients were female. The estimated annual number of hospitalizations because of UTI was 106,508. The incidence was 6.8 per 10,000 for men and 12.4 for women. The median medical care cost was 4250 USD. In-hospital mortality was 4.5%. Risk factors of poor survival included male sex, older age, lower bed capacity, non-academic hospital, admission in winter, higher Charlson Comorbidity Index score, low body mass index, coma on admission, ambulance use, disseminated intravascular coagulation, sepsis, renal failure, heart failure, cerebrovascular diseases, pneumonia, malignancies, use of anti-diabetic drugs, and use of corticosteroid or immunosuppressive drugs. Conclusions We found that older patients of both sexes accounted for a significant proportion of those hospitalized for UTI. The clinical and economic burden of UTI is considerable.

Background In 2017, the Japanese government published an evidence‐based manual describing the appropriate use of antibiotics in outpatient settings to tackle the problem of antimicrobial resistance. To fill the evidence‐practice gap, we developed a clinician‐targeted course aimed at improving clinician skills in the daily clinical practice of treating acute respiratory tract infections (RTIs) based on the manual. The aim of this study was to evaluate the efficacy of the course. Methods This course consisted of lectures using illness scripts and checklists, as well as interactive communication skills training using role‐playing. We performed a vignette‐based evaluation of the changes in the knowledge and attitudes of the course participants toward prescribing antibiotics for nonpneumonia RTIs, using pre‐ and postcourse questionnaires. The questionnaires also included course feedback via the use of a 5‐point Likert scale. Results Thirty‐eight clinicians were included in the analyses, and 90% of these participants had graduated ≥20 years ago. We found statistically significant reductions in the intention to prescribe antibiotics for four of the six nonpneumonia RTI vignettes: acute bronchitis (−47.2%; 95% confidence interval [CI] −66.3 to −28.1%), common cold (−16.2%; 95% CI −30.8 to −1.6%), acute pharyngitis (−27.0%; 95% CI −49.0 to −5.0%), and acute rhinosinusitis (−33.3%; 95% CI −53.3 to −13.3%). The course seemed to be satisfactory for experienced doctors who were the relevant target population of such a workshop. Conclusions The refresher course was helpful for reducing the participants’ intensions to prescribe antibiotics for nonpneumonia RTIs.

There has been scarce evidence about deaths due to blood stream infection (BSI) in Japan so far. The main objective of this study is to understand the epidemiological trend of deaths caused by BSIs due to Staphylococcus aureus and Escherichia coli including Methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FQREC) at national level. We annually estimated the number of BSI caused by S. aureus and E. coli between 2011 and 2017 across Japan using comprehensive data of bacterial culturing and drug susceptibilities collected in Japan Nosocomial Infection Surveillance (JANIS). The number of death was estimated by using BSI mortality obtained from previous studies in Japan. The number of BSI death attributable to S. aureus was estimated to 17,412 in 2011 and 17,157 in 2017, respectively, out of the whole population (126.8 million) in Japan. Among them, cases attributed to MRSA accounted for 5924 (34.0%) in 2011, and decreased to 4224 (24.6%) cases in 2017. On the other hand, the number of BSI death attributable to E. coli was estimated to 9044 in 2011 and increased to 14,016 in 2017. Among them, cases attributed to FQREC accounted for 2045 (22.6%) in 2011 and increased to 3915 (27.9%) cases in 2017. The number of BSI death attributable to MRSA has been decreasing and that attributable to FQREC has been increasing. This study provides the first annual estimate of disease burden of BSI caused by antimicrobial resistant (AMR) bacteria in Japan, and basis for formulating health policy to deal with AMR. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Patients supported by mechanical circulatory support have to wait for longer periods for heart transplantation in Japan. Infective events are a major complication and influence survival. Here, we present the case of a patient with an implantable left ventricular assist device for 6 months who had the complication of ruptured infective common iliac aneurysm. Graft placement with an omental flap was successfully performed via the alternative surgical approach to avoid percutaneous driveline injury. In samples of aortic specimens, 16S ribosomal DNA gene analysis identified Helicobacter cinaedi. Complete removal of the infected tissue and correct pathogen identification may have been relevant to the good clinical course.

In Japan, hospitals' pharmaceutical affairs committees freely select the drugs to be purchased depending on the regulations of each hospital. This system poses a risk of the absence of essential drugs or an excess of similar drugs, and may promote inappropriate use of third-generation cephalosporins (3GCs) and quinolones. Against this backdrop, we researched availability of antibacterial agents in Japanese hospitals. We conducted a questionnaire-based study in eastern Shizuoka Prefecture, Japan. Questionnaires were sent to 33 hospitals that had established an interactive regional partnership on infection control. We analyzed the number of available oral cephalosporins, macrolides, and quinolones in each hospital, and the correlation between the number of total available antibacterial agents and the hospital scale and cephalexin availability. Thirty-one hospitals participated in this study. First-generation cephalosporin (1 GC) was available in only 22.5% of them. In all participating hospitals, 3GCs were available, with more than one 3 GC available in 74.2%. Quinolones were available in all hospitals, and more than one quinolone in 67.7%. The numbers of hospital beds and total available antibacterial agents were positively correlated and hospitals that owned cephalexin available also significantly more often owned other available antibacterial agents. 1 GC were available in only a few hospitals, while multiple 3GCs and quinolones were available in most. This situation may lead to excess use of 3GCs or quinolones in Japan. A low number of available drugs was associated with cephalexin unavailability. Outpatient antimicrobial stewardship may focus not only on the quality of medicine, but also on the prescribing environment.

In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan.

Introduction. This is the first case report of septic abortion due to β-lactamase-negative ampicillin-resistant (BLNAR) non-typeable Haemophilus influenzae infection. In Japan, BLNAR H. influenzae is widespread and has become a clinical concern, especially in paediatrics and otolaryngology, but H. influenzae has not been previously recognized as a causative agent of obstetric or gynaecological infection. Case presentation. A 31-year-old pregnant woman presented at 17 weeks and 6 days of gestation with a high fever; she was admitted with a diagnosis of threatened premature delivery. Despite tocolytic treatment, she aborted spontaneously 2 h after admission and then entered septic shock. BLNAR H. influenzae was detected in both blood and vaginal cultures. Her condition gradually improved after several days of treatment with cefotaxime, and she was ultimately discharged without sequelae or complaints. Conclusion. Although penicillin with a β-lactamase inhibitor is currently recommended for the treatment of septic abortion, this combination will probably lead to treatment failure in the case of BLNAR H. influenzae infection. As this study reveals, H. influenzae can cause septic abortion; hence, future efforts should be undertaken to detect and therapeutically target this pathogen during pregnancy.

Acinetobacter baumannii is generally the most frequently isolated Acinetobacter species. Sequence analysis techniques allow reliable identification of Acinetobacter isolates at the species level. Forty-eight clinical isolates of Acinetobacter spp. were obtained from blood cultures at Tohoku University Hospital. These isolates were identified at the species level by partial sequencing of the RNA polymerase β-subunit ( rpoB ), 16S rRNA, and gyrB genes. Then further characterization was done by using the PCR for detection of OXA-type β-lactamase gene clusters, metallo-β-lactamases, and carO genes. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing were also performed. The most frequent isolate was Acinetobacter soli (27.1%). Six of the 13 A. soli isolates were carbapenem nonsusceptible, and all of these isolates produced IMP-1. PFGE revealed that the 13 A. soli isolates were divided into 8 clusters. This study demonstrated that A. soli accounted for a high proportion of Acinetobacter isolates causing bacteremia at a Japanese tertiary hospital. Non- A. baumannii species were identified more frequently than A. baumannii and carbapenem-nonsusceptible isolates were found among the non- A. baumannii strains. These results emphasize the importance of performing epidemiological investigations of Acinetobacter species.

PurposeInvasive Group G streptococcal infection (iGGS) has increasingly been recognized as a cause of severe disease, mainly among elderly people with chronic illnesses. This study aimed to examine age-related differences in clinical characteristics of iGGS and describe its characteristics among very elderly individuals (≥80 years).MethodsFifty-four iGGS patients for whom detailed clinical information was available were identified from 2002 to 2014 in a tertiary care hospital in Japan. iGGS (n = 54) was compared with invasive Group A (iGAS; n = 17) and B streptococcal infection patients (iGBS; n = 52) based on patient age.ResultsThe incidence of iGGS in our catchment area significantly increased during the study period. The prevalence of iGGS in the very elderly population was higher than that of iGAS or iGBS (pConclusionsThe burden of iGGS has been increasing in our catchment area. Different iGGS-associated clinical characteristics were found in each age group. Unclear and atypical clinical manifestations and syndromes were likely to be observed in very elderly patients. Alcohol drinking and liver cirrhosis may contribute to iGGS even in patients aged

Culture-negative endocarditis remains a diagnostic and therapeutic challenge despite recent medical advances. Streptococcus tigurinus, a novel member of the Streptococcus mitis group, was first identified in Zurich. S. tigurinus possesses virulence determinants and causes invasive infections. We report a case of culture-negative endocarditis with serious complications due to S. tigurinus, which was identified by 16S ribosomal RNA gene sequence analysis of excised valve tissue specimens. This technique is useful for identification of the causative microorganism in patients with culture-negative endocarditis and may facilitate early diagnosis and appropriate antimicrobial treatment.

Background Natural catastrophes increase infectious disease morbidity rates. On March 11, 2011, a 9.0-magnitude earthquake and associated Pacific coast tsunami struck East Japan. The aim of this study was to investigate the characteristics of patients with infectious diseases who needed hospitalization after this disaster. Methods We searched the medical records of 1,577 patients admitted to Tohoku University Hospital in the Sendai area within 1 month (March 11, 2011-April 11, 2011) after the disaster. We examined (1) changes in the rates of hospitalizations for infectious diseases over time and (2) the variety of infectious diseases. Results The number of hospitalized patients with infectious diseases increased after the first week to double that during the same period in 2010. Pneumonia comprised 43% of cases, and 12% consisted of skin and subcutaneous tissue infection, including tetanus. Pneumonia was prevalent in elderly patients (median age, 78 years) with low levels of serum albumin and comorbid conditions, including brain and nervous system disorders. Sputum cultures contained Streptococcus pneumoniae, Moraxella catarrhalis , and Haemophilus influenzae , known pathogens of community-acquired pneumonia in Japan. In addition, 20.5% of patients had positive results for urinary pneumococcal antigen. Conclusions Among hospitalized patients, infectious diseases were significantly increased after the disaster compared with the same period in 2010, with pneumonia being prominent. The analyses suggest that taking appropriate measures for infectious diseases, including pneumonia, may be useful for disaster preparedness and medical response in the future.

On March 11, 2011, the Great East Japan Earthquake – a massive temblor followed by a gigantic tsunami was associated with significant morbidity and mortality. Among many health problems such as trauma, drowning, and mental illnesses, infectious diseases may place significant burden on survivors of such disasters. Wound infections including tetanus, leptospirosis, legionellosis, rickettsiosis, respiratory infections, and diarrheal illness among other infections had been considered to be associated with earthquake and tsunami. Overall, the impact of infectious diseases after the Great East Japan Earthquake was relatively small, with only sporadic outbreaks observed. The incidence of serious infections such as tetanus, legionellosis, and tsunami lung, was also low, considering the overall impact of the earthquake and tsunamiper se. This review discusses the impact of infectious diseases after the Great East Japan Earthquake, and reviews past disaster-related infections as reference.

Background Klebsiella pneumonia is a well-known human pathogen, and recently, a distinct invasive syndrome caused by K. pneumoniae serotypes K1 and K2 has been recognized in Southeast Asia. This syndrome is characterized by primary liver abscess and extrahepatic complications resulting from bacteremic dissemination. We report the first adult case of primary liver abscess caused by the definite K2 serotyped pathogen, with endogenous endophthalmitis in Japan. Case presentation A 64-year-old woman was admitted to a nearby hospital for a high fever and diarrhea. She had visual loss of her right eye, renal dysfunction, and thrombocytopenia within 24 h from admission. She was transferred to our institution. On admission, she had no alteration of mental status and normal vital signs; however, she had almost complete ablepsia of the right eye. Laboratory data showed severe inflammation, liver dysfunction, thrombocytopenia, an increased serum creatinine level, and coagulopathy. Computed tomography showed a low density area in the right lobe of the liver. Invasive liver abscess syndrome probably caused by K. pneumonia was highly suspected and immediately administered broad-spectrum antibiotics for severe sepsis. Concurrently, endogenous endophthalmitis was diagnosed, and we performed vitrectomy on the day of admission. The blood culture showed K. pneumoniae infection. Percutaneous drainage of the liver abscess was also performed. Although she was discharged in a good general condition on day 22, she had complete ablepsia of the right eye. The K2A gene was detected by polymerase chain reaction (PCR), which is consistent with the K2 serotype. PCR was also positive for the virulence-associated gene rmpA. Final diagnosis was invasive liver abscess syndrome caused by K2 serotype K. pneumonia. Conclusions Although the primary liver abscess caused by K. pneumoniae with a hypermucoviscous phenotype is infrequently reported outside Southeast Asia, physicians should recognize this syndrome, and appropriate diagnosis and treatment is essential for saving patients’ lives and preserving organ function, especially for visual acuity.

In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan.

Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused byToxocara canisorToxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA againstToxocaraexcretory-secretory antigen. Only a corticosteroid was used in Case 1, whereas a corticosteroid and albendazole were used in Case 2 as induction therapy. Both patients recovered. Albendazole was also used in Case 1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole.

Background Antimicrobial resistance (AMR) is a threat to global health. To increase public awareness about AMR and encourage the prudent use of antimicrobials is one of the goals of the National Action Plan in Japan. Methods A nationwide online cross-sectional survey was conducted to evaluate the existing knowledge and perception of AMR in Japan, based on the Antimicrobial Resistance Eurobarometer Survey. Participants included Japanese adults aged 20–69 years, who were not medical professionals. Results Among a total of 3,390 participants, about half had taken antibiotics over the past 12 months, and majority of them obtained the antimicrobials from healthcare institutions for the common cold. While 11.7% of the participants kept leftover antibiotics, 23.6% of them have adjusted doses by themselves. About 10% of the participants have requested antibiotics from their doctors, and nearly 30% of them preferred doctors who prescribed antibiotics when had a cold. The common informational sources were TV news and newspapers, and more than 40% of the participants reported receiving some information over the past year. However, approximately 80% of the participants did not know that antibiotics do not kill viruses and that antibiotics are ineffective against cold and flu. Conclusion Not many Japanese have adequate information about antimicrobials and AMR, and many have taken antimicrobials inappropriately. Greater educational interventions are, therefore, necessary to increase public awareness and develop effective countermeasures against AMR in Japan.

Cryptococcal lung disease is usually diagnosed by chest X-ray abnormalities. Although no treatment exists for asymptomatically immunocompetent patients, a case with central nervous system (CNS) involvement as cryptococcus dissemination had a new chest X-ray abnormality during marked eosinophilia diagnosed as pulmonary cryptococcosis by lung biopsy. Eosinophilia may thus be associated with pulmonary cryptococcosis. We had seen reports of disseminated cryptococcosis with eosinophilia, so we conducted lumbar puncture and blood culture, but found no disseminated lesion or CNS involvement. Eosinophilia association with disseminated cryptococcosis has been reported, but not pulmonary cryptococcosis with solitary localized lung lesion with marked eosinophilia, making our case the first, in so far as we know reported of pulmonary cryptococcosis with a solitary localized lung lesion with marked eosinophilia.

Pseudomonas aeruginosa, the leading nosocomial pneumonia pathogen in immunocompromised patients, has Recently become typically presented as slowly progressive ventilator-associated pneumonia. We report two cases of bacteremic pneumonia due to Pseudomonas aeruginosa in non-neutropenic solid-organ cancer. Both subjects had sudden sepsis or septic shock but few respiratory symptoms. Chest radiography showed a diffuse unilateral decrease in permeability, becoming necrotizing pneumonia and lung abscess in 7-10 days. Conventional literature describe fulminant pseudomonas bacteremic pneumonia in non-neutropenic immunocompromised hosts as the initial presentation with septic shock and interstitial lung opacity, leading lung abscess.

Tuberculosis was diagnosed in a person who had stayed in a shelter after the 2011 Great East Japan Earthquake. A contact investigation showed that the prevalence of latent tuberculosis infection among other evacuees at the shelter was 20%. Our report underscores the importance of tuberculosis prevention and control after natural disasters.

We describe 2 post-tsunami outbreaks of influenza A in evacuation centers in Miyagi Prefecture, Japan, in 2011. Although containment of the outbreak was challenging in the evacuation settings, prompt implementation of a systemic approach with a bundle of control measures was important to control the influenza outbreaks.

Susceptible healthcare personnel (HCP) are at high risk for acquiring and transmitting measles, mumps, rubella, and varicella (MMRV). Presumptive evidence of immunity to MMRV is recommended for HCP. The aim of this investigation was to examine the seroprevalence of MMRV in Japanese HCP and the association with history or vaccination in terms of occupational safety. To improve infection control at our hospital, we also assessed their immune status by implementing prevaccination antibody screening and an immunization program with postvaccination serological testing. We implemented seroprevalence surveys on MMRV antibodies among 243 newly and 2,664 previously hired HCP in a Japanese tertiary care hospital. Self-administered questionnaires about history of MMRV and vaccination with or without written documentation were completed for newly hired HCP. Prevaccination and postvaccination serological tests were performed using virus-specific IgG enzyme-linked immunosorbent assays. Indeed, only a few HCP accurately remembered or had written records of their disease or vaccination history. After our immunization program was implemented, the seropositivity rate reached levels as high as ~98% for measles, rubella, and varicella, and increased to ~80% for mumps. Our program was cost-effective, and no severe adverse reactions were reported. The prevaccination antibody screening for HCP would be helpful, given the lack of written vaccination records or documented disease history, and is also useful for the prevention of adverse reactions associated with unnecessary vaccination. It is important for infection control practitioners to comprehend the immune status of HCP against MMRV, and then provide an appropriate immunization program for susceptible HCP.

In cooperation with the Miyagi prefectural government, we conducted a survey of the management of sanitation at evacuation centers and the health of the evacuees by visiting 324 evacuation centers at two weeks after the 2011 Great East Japan Earthquake. The facilities often used as evacuation centers were community centers (36%), schools (32.7%) and Nursing homes (10.2%). It was more difficult to maintain a distance of at least 1 m between evacuees at the evacuation centers with a larger number of residents. At evacuation centers where the water supply was not restored, hygienic handling of food and the hand hygiene of the cooks were less than adequate. Among evacuation centers with ≤50 evacuees, there was a significant difference in the prevalence rate of digestive symptoms between the centers with and without persons in charge of health matters (0.3% vs. 2.1%, respectively, p < 0.001). The following three factors had an important influence on the level of sanitation at evacuation centers and the health of evacuees: 1) the size of the evacuation center, 2) the status of the water supply, and 3) the allocation of persons in charge of health matters. Given that adjusting the number of evacuees to fit the size of the evacuation center and prompt restoration of the water supply are difficult to achieve immediately after an earthquake, promptly placing persons in charge of health matters at evacuation centers is a practicable and effective measure, and allocation of at least one such person per 50 evacuees is desirable.

Over-expression of alpha-phenol-soluble modulins (PSMs) results in high virulence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). The psm-mec gene, located in the mobile genetic element SCCmec-II, suppresses PSMαs production. Fifty-two patients with MRSA bacteraemia were enrolled. MRSA isolates were evaluated with regard to the psm-mec gene sequence, bacterial virulence, and the minimum inhibitory concentration (MIC) of vancomycin and teicoplanin. Fifty-one MRSA isolates were classified as SCCmec-II, and 10 had one point mutation in the psm-mec promoter. We compared clinical characteristics and outcomes between mutant MRSA and wild-type MRSA. Production of PSMα3 in mutant MRSA was significantly increased, but biofilm formation was suppressed. Wild-type MRSA caused more catheter-related bloodstream infections (30/41 vs. 3/10, p 0.0028), whereas mutant MRSA formed more deep abscesses (4/10 vs. 3/41, p 0.035). Bacteraemia caused by mutant MRSA was associated with reduced 30-day mortality (1/10 vs. 13/41, p 0.25), although this difference was not significant. The MIC90 of teicoplanin was higher for wild-type MRSA (1.5 mg/L vs. 1 mg/L), but the MIC of vancomycin was not different between the two groups. The 30-day mortality of MRSA with a high MIC of teicoplanin (≥1.5 mg/L) was higher than that of strains with a lower MIC (≤0.75 mg/L) (6/10 vs. 6/33, p 0.017). Mutation of the psm-mec promoter contributes to virulence of SCCmec-II MRSA, and the product of psm-mec may determine the clinical characteristics of bacteraemia caused by SCCmec-II MRSA, but it does not affect mortality.

The characteristics of active tuberculosis in cancer patients in Japan and the effects of this infection on cancer treatment have not yet been clarified. The records of all consecutive patients with microbiologically documented Mycobacterium tuberculosis infection diagnosed between September 2002 and March 2008 at Shizuoka cancer center (a 557-bed tertiary care cancer center in Japan) were reviewed. There were 24 cancer patients with active tuberculosis during the study period. Of these, 23 had solid-organ tumors, and the most common site of the underlying malignancy was the lung. Most of the patients had pulmonary tuberculosis. Among 15 patients followed up for more than 2 months prior to the diagnosis of pulmonary tuberculosis, 12 had healed scars suggestive of old tuberculosis lesions, as shown by chest imaging obtained at the time of the initial evaluation. Discontinuation of cancer therapy or more than a month's delay in surgery occurred in 10 patients with pulmonary tuberculosis. Development of active tuberculosis can delay cancer treatment in Japanese centers. Cancer patients with scars suggestive of old tuberculosis disease lesions as shown by chest imaging should be screened for active tuberculosis and carefully followed up. In some cases, prophylactic treatment should be considered.

The prevalence of ESBL has been increasing worldwide. In this study, we investigated the molecular characteristics of ESBL among clinical isolates of Escherichia coli from a Japanese tertiary hospital. A total of 71 consecutive and nonduplicate clinical isolates of ESBL-positive E. coli collected at Tohoku University Hospital between January 2008 and March 2011 were studied. The antimicrobial susceptibility profile of these strains was determined. PCR and sequencing were performed to identify genes for β-lactamase (bla(TEM), bla(SHV), bla(OXA-1-like), and bla(CTX-M)) and plasmid-mediated quinolone resistance determinants (PMQR). The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Of the 71 strains, 68 were positive for CTX-M, 28 were positive for TEM, four were positive for OXA-1, and one was positive for SHV. Sequencing revealed that CTX-M-14 was the most prevalent (31/71), followed by CTX-M-27 (21/71) and then CTX-M-15 (9/71). Of the 28 TEM-positive strains, one was TEM-10 and the rest were TEM-1. One SHV-positive strain was SHV-12. The 21 CTX-M-27-producing isolates were divided into 14 unique PFGE types, while the 9 CTX-M-15 producers were divided into 8 types. Based on MLST, 9 CTX-M-14 procedures, 19 CTX-M-27 procedures, and 8 CTX-M-15 producers belonged to ST131. Thirty-five (94.6%) of the 37 ST131 E. coli strains showed resistance to levofloxacin, which was a higher rate than among non-ST131 strains (63.6%). Among ESBL-producing isolates, one, two, and six possessed qnrB, qnrS, qepA, and aac(6')-Ib-cr, respectively. Of the 6 isolates with aac(6')-Ib-cr, 4 carried the CTX-M-15 gene. Our data suggest that CTX-M-15-producing E. coli ST131 has emerged as a worldwide pandemic clone, while CTX-M-27 (a variant of CTX-M-14) is also spreading among E. coli ST131 in Japan.

Natural catastrophes increase infectious disease morbidity rates. On March 11, 2011, a 9.0-magnitude earthquake and associated Pacific coast tsunami struck East Japan. The aim of this study was to investigate the characteristics of patients with infectious diseases who needed hospitalization after this disaster.We searched the medical records of 1,577 patients admitted to Tohoku University Hospital in the Sendai area within 1 month (March 11, 2011-April 11, 2011) after the disaster. We examined (1) changes in the rates of hospitalizations for infectious diseases over time and (2) the variety of infectious diseases.The number of hospitalized patients with infectious diseases increased after the fi rst week to double that during the same period in 2010. Pneumonia comprised 43% of cases, and 12% consisted of skin and subcutaneous tissue infection, including tetanus. Pneumonia was prevalent in elderly patients (median age, 78 years) with low levels of serum albumin and comorbid conditions, including brain and nervous system disorders. Sputum cultures contained Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae , known pathogens of community-acquired pneumonia in Japan. In addition, 20.5% of patients had positive results for urinary pneumococcal antigen.Among hospitalized patients, infectious diseases were significantly increased after the disaster compared with the same period in 2010, with pneumonia being prominent. The analyses suggest that taking appropriate measures for infectious diseases, including pneumonia, may be useful for disaster preparedness and medical response in the future.