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Abstract Introduction Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients. Methods This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015–March 2020) to identify IED cases among patients aged ≥ 60 years. IED was defined as a positive E. coli culture in blood or other normally sterile body site (group 1 IED) or positive culture of E. coli in urine with signs of sepsis (group 2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts. Results A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79 years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9 days; non-Asian 95%, mean duration 6.8 days), with frequent admission to intensive care (Asian 35%, mean duration 3.3 days; non-Asian 34%, mean duration 3.5 days), all standardized differences [SD]

This study evaluating the efficacy of coronavirus disease 2019 contact tracing in the hospital setting during the omicron variant era found a high incidence of nosocomial severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission in outbreaks, especially among individuals having close contact with infected persons. Identifying close contacts and outbreaks is essential to prevent nosocomial SARS-CoV-2 transmission.

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

IntroductionThe prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan.MethodsCarbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates.ResultsEleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes.DiscussionThe findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination.

Abstract 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.

BackgroundBoth physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. Although many countries have national influenza surveillance systems, data on nationwide prescription practices of anti-influenza drugs are lacking. Therefore, we aimed to clarify the status of anti-influenza drug use in Japan 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, which drugs they were prescribed, the patients' 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 estimated 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, with men were more likely than women to be prescribed anti-influenza drugs while hospitalized.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.

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.

Abstract 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.

Abstract Background The goals of the National Action Plan on Antimicrobial Resistance (AMR) of Japan include “implementing appropriate infection prevention and control” and “appropriate use of antimicrobials,” which are relevant to healthcare facilities. Specifically, linking efforts between existing infection control teams and antimicrobial stewardship programs was suggested to be important. Previous studies reported that human resources, such as full-time equivalents of infection control practitioners, were related to improvements in antimicrobial stewardship. Methods We posted questionnaires to all teaching hospitals (n = 1017) regarding hospital countermeasures against AMR and infections. To evaluate changes over time, surveys were conducted twice (1st survey: Nov 2016, 2nd survey: Feb 2018). A latent transition analysis (LTA) was performed to identify latent statuses, which refer to underlying subgroups of hospitals, and effects of the number of members in infection control teams per bed on being in the better statuses. Results The number of valid responses was 678 (response rate, 66.7%) for the 1st survey and 559 (55.0%) for the 2nd survey. More than 99% of participating hospitals had infection control teams, with differences in activity among hospitals. Roughly 70% had their own intervention criteria for antibiotics therapies, whereas only about 60 and 50% had criteria established for the use of anti-methicillin-resistant Staphylococcus aureus antibiotics and broad-spectrum antibiotics, respectively. Only 50 and 40% of hospitals conducted surveillance of catheter-associated urinary tract infections and ventilator-associated pneumonia, respectively. Less than 50% of hospitals used maximal barrier precautions for central line catheter insertion. The LTA identified five latent statuses. The membership probability of the most favorable status in the 2nd study period was slightly increased from the 1st study period (23.6 to 25.3%). However, the increase in the least favorable status was higher (26.3 to 31.8%). Results of the LTA did not support a relationship between increasing the number of infection control practitioners per bed, which is reportedly related to improvements in antimicrobial stewardship, and being in more favorable latent statuses. Conclusions Our results suggest the need for more comprehensive antimicrobial stewardship programs and increased surveillance activities for healthcare-associated infections to improve antimicrobial stewardship and infection control in hospitals.

Abstract Background In 2018, the Japanese medical reimbursement system was revised to introduce a fee for the implementation of an antimicrobial stewardship (AS) fee for pediatric patients. The purpose of this study was to evaluate physicians’ prescription behavior following this revision. Methods We conducted a retrospective observational study from January 1, 2017 to September 30, 2018 of pediatric (

Abstract 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. 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.

The threat from antimicrobial resistance (AMR) continues to grow. Japan’s National Action Plan on Antimicrobial Resistance, which was formulated in 2016 and targets six areas, has already had a major impact on the countermeasures implemented against AMR. Particular advances have been made in AMR-related surveillance, and we now know the situation regarding antimicrobial use and antimicrobial-resistant bacteria in the country. Educational and awareness-raising activities for medical professionals and the general public have been actively implemented and seem to have contributed to a gradual move toward an appropriate use of antimicrobials. However, there is still insufficient understanding of the issue among the general public. Determining how to use surveillance results and implementing further awareness-raising activities are crucial to address this. Tasks for the future include both raising awareness and the promotion of AMR research and development and international cooperation. The government’s next Action Plan, which will detail future countermeasures against AMR based on the outcomes of and tasks identified in the current Action Plan, has been delayed due to the COVID-19 pandemic and is urgently awaited.

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

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux.

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.

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 by Toxocara canis or Toxocara 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 against Toxocara excretory-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.

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.

The public health community is faced with the global challenge posed by antimicrobial-resistant bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum b-lactamases (ESBLs)-producing enterobacteriaceae. The need to address this issue prompted the focus of World Health Day 2011, which was entitled “Antimicrobial resistance: no action today, no cure tomorrow.”In today’s world of international travel, the globalization of drug-resistant bacteria is a pressing issue for public health professionals. In the World Health Organization (WHO) Western Pacific Region, as well as other regions in the world, more and more new types of antimicrobial-resistant bacteria have come to the forefront. An important example is New Delhi Metallo-b-lactamase 1 (NDM-1)-carrying enterobacteriaceae, which attracted attention in Europe in 2010 as imported cases associated with health care contact in India and Bangladesh. Although some NDM-1 cases were reported from Australia and Japan,2 no outbreaks were reported in the Western Pacific Region.In this perspective article, we consider four focus areas for countries in the Western Pacific Region to consider when strategizing their response to antimicrobial resistant bacteria.

During an epidemiologic investigation of pandemic influenza (H1N1) 2009 virus infection in May 2009 in Osaka, Japan, we found 3 clusters in which virus transmission occurred during the presymptomatic phase. This finding has public health implications because it indicates that viral transmission in communities cannot be prevented solely by isolating symptomatic case-patients.

Influenza-associated encephalopathy (IAE) is a serious complication of influenza and is reported most frequently in Japan. This paper presents an assessment of the epidemiological characteristics of influenza A (H1N1) 2009-associated encephalopathy in comparison to seasonal IAE, based on Japanese national surveillance data of influenza-like illness (ILI) and IAE during flu seasons from 2004-2005 through 2009-2010. In each season before the pandemic, 34-55 IAE cases (mean 47.8; 95% confidence interval: 36.1-59.4) were reported, and these cases increased drastically to 331 during the 2009 pandemic (6.9-fold the previous seasons). Of the 331 IAE cases, 322 cases were reported as influenza A (H1N1) 2009-associated encephalopathy. The peaks of IAE were consistent with the peaks of the influenza epidemics and pandemics. A total of 570 cases of IAE (seasonal A, 170; seasonal B, 50; influenza A (H1N1) 2009, 322; unknown, 28) were reported over six seasons. The case fatality rate (CFR) ranged from 4.8 to 18.2% before the pandemic seasons and 3.6% in the 2009 pandemic season. The CFR of pandemic-IAE was 3.7%, which is lower than that of influenza A-/B-associated encephalopathy (12.9%, p

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.

The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing bla(CTX-M), bla(SHV), or bla(TEM) were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan.

Introduction: The prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan. Methods: Carbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates. Results: Eleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes. Discussion: The findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination. [ABSTRACT FROM AUTHOR]