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Background An audiovisual telesupport system that enables real-time audiovisual communications between 2 long-distance hospitals is one method of telemedicine. The usefulness and safety of radiofrequency catheter ablation (RFCA) using an audiovisual telesupport system has not been well established. Objective The purpose of this study was to evaluate the effectiveness and safety of RFCA using an audiovisual telesupport system. Methods An audiovisual telesupport system using a strictly secured virtual network was established between Kamisu Saiseikai Hospital (operator with 10 years' experience and 800 procedures) and the University of Tsukuba (advisor with >20 years' experience and 8000 procedures). We evaluated 19 initial consecutive patients who underwent RFCA using this system for tachyarrhythmia: 10 with atrial fibrillation (AF), 5 with paroxysmal supraventricular tachycardia (PSVT), 3 with premature ventricular contraction (PVC), and 1 with atrial flutter. Electrophysiological and procedural characteristics were retrospectively assessed. Results Acute success was achieved in all 19 patients without any major complications, with the advisor's audiovisual assistance. Mean procedure time and fluoroscopic time were 161 ± 44 minutes and 24 ± 14 minutes for AF, 110 ± 17 minutes and 28 ± 8 minutes for PVC, and 132 ± 19 minutes and 32 ± 2 minutes for PSVT, respectively. There was no recurrence of clinical arrhythmia in 17 of the 19 patients (89%) during 13 ± 9 month follow-up. Conclusion An audiovisual telesupport system for RFCA is a useful and safe method that enabled the electrophysiologist with limited human resources to make an optimal decision regarding procedural strategy and endpoint with the remote advisor's audiovisual assistance.

The pulse wave transit time (PWTT) is easily measured as the time from the R wave of an electrocardiogram to the arrival of the pulse wave measured by an oxygen saturation monitor at the earlobe. We investigated whether the change of PWTT during exercise testing reflects cardiopulmonary function. Eighty-nine cardiac patients who underwent cardiopulmonary exercise testing (CPX) were enrolled. We analyzed the change of PWTT during exercise and the relationship between the shortening of the PWTT and CPX parameters. PWTT was significantly shortened from rest to peak exercise (204.6 ± 33.6 vs. 145.6 ± 26.4 msec, p < 0.001) in all of the subjects. The patients with heart failure had significantly higher PWTT at peak exercise than the patients without heart failure (152.7 ± 27.1 vs. 140.4 ± 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak exercise showed significant positive correlations with the peak O2 uptake (VO2) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016), and % increase of systolic blood pressure during exercise (r = 0.75, p < 0.001), and a negative correlation with the slope of the increase in ventilation versus the increase in CO2 output (VE-VCO2 slope) (r = - 0.42, p = 0.010) in the patients with heart failure. PWTT was shortened during exercise as the exercise intensity increased. In the patients with heart failure, the shortening of PWTT from rest to peak exercise was smaller in those with lower exercise capacity and those with higher VE-VCO2 slope, an established index known to reflect the severity of heart failure.

Obligate anaerobes exist as resident flora in various sites in humans, but they are also emphasized as endogenous causative microorganism of infections. We performed surveillance to understand the trend of drug susceptibility in obligate anaerobic bacteria in the Kinki area of Japan. In the experiment, we used 156 obligate anaerobe isolates collected from 13 institutions that participated in the Study of Bacterial Resistance Kinki Region of Japan. MALDI Biotyper was used to identify the collected strains, and among the 156 test strains, those that could be identified with an accuracy of Score Value 2.0 or more included 6 genera, 30 species, and 144 strains (Bacteroides spp. 77 strains, Parabacteroides sp. 2 strains, Prevotella spp. 29 strains, Fusobacterium spp. 14 strains, Porphyromonas spp. 2 strains, and Clostridioides difficile 20 strains), and they were assigned as subject strains for drug susceptibility testing. The drug susceptibility test was carried out by broth microdilution method using Kyokuto Opt Panel MP ANA (Kyokuto Pharmaceutical Industrial Co., Ltd., Tokyo, Japan) and judged according to CLSI criteria. As a result, Bacteroides and Parabacteroides species showed good sensitivities to tazobactam-piperacillin, imipenem, metronidazole and chloramphenicol, and low sensitivities to ampicillin, cefoperazone and vancomycin. Prevotella species showed good sensitivities to sulbactam-ampicillin, tazobactam-piperacillin, cefmetazole, imipenem, doripenem and metronidazole. Susceptibility rates to other drugs were slightly different depending on the bacterial species. Both Fusobacterium spp. and Porphyromonas spp. showed high sensitivities to many drugs. C. difficile was highly sensitive to vancomycin and metronidazole, having MIC90s of 0.5 μg/mL and ≤2 μg/mL, respectively.

The spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a serious threat to clinical practice and public health. These bacteria are present both in clinical settings and non-clinical environments. The presence of CPE in food stuffs has been reported, but sporadically so. Here, we screened for CPE in meat, seafood, and vegetable samples from local markets of Yangon, Myanmar. We obtained 27 CPE isolates from 93 food samples and identified 13 as Escherichia coli, six as Klebsiella pneumoniae, seven as Enterobacter cloacae complex, and one as Serratia marcescens. All except the E. cloacae complex harboured the carbapenemase genes blaNDM-1 or blaNDM-5, while all Enterobacter isolates carried the carbapenemase gene blaIMI-1. The blaIMI-1 gene was located in putative mobile elements EcloIMEX-2, -3, or -8. Using multi-locus sequence typing, E. coli, K. pneumoniae, and E. cloacae complex isolates were classified into 10, six, and five different sequence types, respectively. Our results demonstrate that diverse organisms with various carbapenemase genes are widespread in the market foods in Yangon, highlighting the need for promoting proper food hygiene and effective measures to prevent further dissemination.

Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.

Aims The objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long‐term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly. Methods and results Overall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study‐HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All‐cause mortality was compared between the low GNRI (

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings. A large-scale multiclonal VRE outbreak has rarely been reported in Japan due to low VRE prevalence. We evaluated the transmission of vancomycin resistance in a multiclonal VRE outbreak, conducted biological and genomic analyses of VRE isolates, and assessed the implemented infection control measures. In total, 149 patients harboring VanA-type VRE were identified from April 2017 to October 2019, with 153 vancomycin-resistant Enterococcus faecium isolated being grouped into 31 pulsotypes using pulsed-field gel electrophoresis, wherein six sequence types belonged to clonal complex 17. Epidemic clones varied throughout the outbreak; however, they all carried vanA-plasmids (pIHVA). pIHVA is a linear plasmid, carrying a unique structural Tn1546 containing vanA; it moves between different Enterococcus spp. by genetic rearrangements. VRE infection incidence among patients in the “hot spot” ward correlated with the local VRE colonization prevalence. Local prevalence also correlated with vancomycin usage in the ward. Transmission of a novel transferrable vanA-plasmid among Enterococcus spp. resulted in genomic diversity in VRE in a non-endemic setting. The prevalence of VRE colonization and vancomycin usage at the ward level may serve as VRE cross-transmission indicators in non-intensive care units for outbreak control.

Urinary antigen tests are a widely used rapid diagnostic method for Legionella pneumonia. However, conventional urinary antigen tests are unable to detect anything other than Legionella pneumophila serogroup 1. The Ribotest Legionella (Ribotest) can detect all serogroups by using antibodies recognizing L. pneumophila ribosomal protein L7/L12 in addition to the conventional L. pneumophila serogroup 1 lipopolysaccharide. The aim of this study was to evaluate the performance of Ribotest against conventional urinary antigen tests, including the detection of Legionellaceae other than L. pneumophila. We investigated the detection sensitivity of various kits using in-vitro culture-soluble antigen extracts of ATCC strains and 22 clinical isolates collected from multiple medical facilities in the Kinki region of Japan. For L. pneumophila serogroup 1, four kits, including Ribotest, had a detection sensitivity of 105 CFU/mL, with only Check Legionella having a sensitivity of 106 CFU/mL. L. pneumophila non-serogroup 1 and Legionellaceae of other species were undetectable by the four conventional kits, whereas Ribotest could detect them with a sensitivity of 105–108 CFU/mL. The Ribotest was also able to detect other species such as Legionella hackeliae, Legionella feeleii, Legionella anisa, Fluoribacter bozemanae, and Fluoribacter dumoffii, but the detection sensitivity of L. hackeliae and L. feeleii was 108 CFU/mL, which was much lower than that of the other strains. The Ribotest has high potential to be applied as a rapid diagnostic method for pneumonia caused by other species of Legionella and Fluoribacter.

Background Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking. Methods and Results A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102–3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066). Conclusions This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing at medical institutions in Japan without even noticing. Recently, we performed a point prevalence survey for CRE carriage at a medical facility in northern Osaka that demonstrated an unexpectedly high prevalence of blaIMP-6-positive CRE, particularly at long-term care hospitals (LTCH). To identify the risk factors for CRE carriage, we collected clinical data of patients at a representative LTCH. Of 140 patients who were included in this study, 27 (19.3%) were colonized with metallo-beta-lactamase (IMP-6) producers. Pulsed-field gel electrophoresis of the IMP-6 producing Enterobacteriaceae suggested a non-clonal transmission of Escherichia coli, while a clonal spread was shown for Klebsiella pneumoniae. Risk factors for CRE colonization were a longer stay at the hospital stay and a lower independence state, as measured by Norton scales. We propose that a paradigm shift in infection control, inciting a coordinated regional effort to involve LTCHs, should be discussed in the aging society of Japan.

An NDM-5-producing Klebsiella pneumoniae ST147 strain was isolated from a Japanese patient who had not travelled abroad in at least 5 years. Whole-genome sequencing revealed a genomic rearrangement in an FII plasmid harbouring bla NDM-5 due to the replicative transposition of IS26. A hypothetical structure was proposed for its ancestral plasmid, and comparative genomic analysis of the plasmid suggested the dissemination of structurally similar plasmids harbouring bla NDM-5 in Asian and Middle Eastern countries.

Ventilation (VE) increases linearly with the increase of carbon dioxide output (VCO2) during cardiopulmonary exercise testing. VE-VCO2 slope rises in parallel with exercise intensity, reaches a turning point (called the RC point), then steepens because of respiratory compensation for lactic acidosis. While this RC point can be identified universally, it is undetectable in some patients. In this study we evaluated whether the respiratory compensation during exercise testing has clinical significance in cardiac patients. In total, 152 cardiac patients with a respiratory exchange ratio at peak exercise (peak R) of between 1.10 and 1.20 were enrolled. Cardiopulmonary parameters were compared between patients who manifested the RC point (n = 118) and those who did not (n = 34). The peak R did not significantly differ between these two groups. Compared to the patients without the RC point, those with the RC point had a higher oxygen uptake at peak exercise (peak VO2) (20.2 ± 5.3 vs 13.6 ± 3.4 mL/min/kg, p < 0.001), higher anaerobic threshold (AT) (12.4 ± 3.2 vs 9.2 ± 2.3 mL/min/kg, p < 0.001), and lower VE-VCO2 slope (31.7 ± 5.8 vs 37.8 ± 9.6, p = 0.001). Brain natriuretic peptide (BNP) tended to be lower in the patients with the RC point (175.4 ± 364.7 vs 327.9 ± 381.1 pg/mL, p = 0.067). Peak VO2, the marker of cardiopulmonary function, was found to be the independent predictor of the presence of the RC point. The present findings suggest that the phenomenon of respiratory compensation during heavy exercise indicates better cardiopulmonary function in cardiac patients within a prescribed range of effort.

We describe a rare case of Propionibacterium acnes native-valve endocarditis that silently progressed in a 67-year-old man with hybrid dialysis. The patient was scheduled for kidney transplantation, and pre-operative investigation incidentally detected a vegetative structure at his native mitral valve that had increased in size. He underwent cardiac surgery and P. acnes was detected in cultures of a resected cardiac valve specimen and blood. This case highlights that P. acnes can silently cause infective endocarditis in a native-valve, and that physicians should consider the possibility of infection when P. acnes is isolated in blood cultures.

Cardiac patients often experience nocturnal and daytime oscillatory breathing (OB). OB noted at rest sometimes becomes unclear or even disappears during exercise. We evaluated the physiological significance of OB by comparing the clinical characteristics of cardiac patients who manifested OB only at rest (group A), only during exercise (group B), and both at rest and during exercise (group C).Among 3,432 cardiac patients who underwent cardiopulmonary exercise testing (CPX), 114, 94, and 65 patients were identified as group A, B, and C, respectively. Left ventricular ejection function was 57 ± 17% in group A, 49 ± 20% in group B, and 41 ± 21% in group C (P < 0.05 for all comparisons among the 3 groups). The level of brain natriuretic peptide (BNP) was significantly higher in group C than in groups A and B. The peak VO2 was lower and the VE-VCO2 slope was higher in groups B and C than in group A.The present findings suggest that cardiac function is more impaired in cardiac patients who manifest OB both at rest and during exercise than in cardiac patients who manifest OB only at rest or only during exercise.

Carbapenemase-producing Enterobacteriaceae (CPE) are increasing worldwide. Rapid and accurate detection of CPE is necessary for appropriate antimicrobial treatment and hospital infection control. However, CPE contains some strains that are difficult to detect depending on genotype and MIC value of carbapenem, and a detection method has not been established. The recently reported modified carbapenem inactivation method (mCIM) has been developed in CLSI M100-S27 as a phenotypic technique for detecting carbapenemase activity. In the present study, we examined mCIM as a new CPE detection method using 207 Enterobacteriaceae isolates in comparison with the three existing screening methods of modified Hodge test, Carba NP test and carbapenem inactivation method and evaluated its performance. Consequently, both the sensitivity and specificity of mCIM were 100%, indicating better results than the conventional screening methods. The mCIM is a useful tool for microbiology laboratories due to its simplicity, clear criteria, cost-effectiveness and availability at any laboratory.

Corynebacterium striatum, generally considered an opportunistic organism in humans, has recently been known to develop high-level daptomycin resistance (HLDR) shortly after drug exposure. To date, however, only several such clinical isolates have been described in the literature and clinical background of the resistant pathogen remains to be elucidated. Here, we report a case involving a C. striatum strain with HLDR harboring novel nucleotide mutations, together with a review of the relevant literature. To the best of our knowledge, this is the first well-investigated clinical report from Japan including a genetic investigation. Considering the rapid emergence of HLDR C. striatum in vitro experiment, there could be a number of underreporting cases. Scrupulous attention is required when administering daptomycin for the treatment of C. striatum infections, even if the organism has initially exhibited susceptibility.

Pasteurella multocida, a zoonotic pathogen in humans, is known to be associated with skin and soft tissue infections following animal bites, but rarely causes visceral infections. We report a case of P. multocida-associated multiple intrapelvic abscesses in a young woman with uterine cervical cancer. A 29-year-old unmarried woman was referred to us because of prolonged high fever accompanying abdominal pain with muscular guarding. She had a domestic cat but denied of any bites or scratches before that. Computed tomography demonstrated ascites and multiple abscesses around her uterus. Her condition did not improve with an initial treatment with flomoxef, clindamycin, and azithromycin. Further, we performed percutaneous pus drainage and switched the antimicrobial therapy to a combination of piperacillin/tazobactam and minocycline for 10 days. Although P. multocida was isolated from vaginal culture, no organisms were isolated from the pus culture. However, further investigation with specimen-direct 16S rDNA analysis diagnosed P. multocida as possibly a single pathogen responsible for the intrapelvic infection. After taking oral levofloxacin for two weeks, no recurrence was reported. Although P. multocida is known as an animal-related pathogen, it can transmit to humans without apparent bites or scratches. The present case illustrates that P. multocida can cause intrapelvic abscess as a result of ascending genital infection.

Controlling nutritional status (CONUT) uses 2 biochemical parameters (serum albumin and cholesterol level), and 1 immune parameter (total lymphocyte count) to assess nutritional status. This study examined if CONUT could predict the short-term prognosis of heart failure (HF) patients.A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (n = 838) were enrolled (298 men, 71.7 ± 13.6 years). Blood samples were collected at admission, and nutritional status was assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe degree of undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. The logarithmically transformed plasma brain natriuretic peptide (log BNP) concentration was significantly higher in the moderate-severe nutritional disturbance group (2.92 ± 0.42) compared to the normal group (2.72 ± 0.45, P < 0.01). CONUT scores were significantly higher in the in-hospital death patients [4 (3-8), n = 14] compared with patients who were discharged following symptom alleviation [3 (1-5), n = 446, P < 0.05]. With the exception of transferred HF patients (n = 22), logistic regression analysis that incorporated the CONUT score and the log BNP, showed that a higher CONUT score (P = 0.019) and higher log BNP (P = 0.009) were predictors of in-hospital death, and the median duration of hospital stay was 20 days.Our results demonstrate the usefulness of CONUT scores as predictors of short-term prognosis in hospitalized HF patients.

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported to be lower in Japan than in many other countries. However, extensive surveillance for CRE carriage has not been performed in Japan.To investigate the prevalence of CRE carriage in Japan among convalescent patients considered to be at high risk of being CRE carriers using an improved selective culture medium.A cross-sectional survey was conducted in 22 acute care hospitals (ACHs) and 21 long-term care hospitals (LTCHs) in northern Osaka from December 2015 to January 2016. Patients who used incontinence aids, an enteral feeding tube or a urinary catheter were enrolled. Faecal specimens were examined using the newly developed M-ECC for imipenemase (IMP)-producing CRE, which is the most prevalent form of CRE in Japan. The positive isolates were analysed by polymerase chain reaction and sequencing. Risk factors associated with carriage were analysed by logistic regression.Among 1507 patients, 184 (12.2%) carried CRE. The percentage of positive patients was significantly higher in LTCHs (14.9%) than in ACHs (3.6%) (P0.001). Risk factors for CRE carriage were longer hospital stay [odds ratio (OR) 2.59; 95% confidence interval (CI) 1.87-3.60], enteral feeding (OR 3.03, 95% CI 2.08-4.42) and antibiotic exposure (OR 2.00, 95% CI 1.40-2.87). Among the 233 CRE isolates identified, 223 were IMP producers; the remaining isolates did not produce carbapenemase.This is the first Japanese report to demonstrate the significant spread of CRE in both ACHs and LTCHs using an improved selective medium. A coordinated regional approach may help to prevent further spread.

Clinical impact of changes of renal function (RF) in heart failure (HF) hospitalization is controversial. This study aimed to clarify whether clinical impact of changes of RF during HF hospitalization depends on the intrinsic RF. In 786 hospitalized HF patients, RF were classified into 3 grades based on estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) at discharge; ≥ 60 (n = 243)

The spread of carbapenemase-producing Enterobacteriaceae (CPE), contributing to widespread carbapenem resistance, has become a global concern. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring bla(NDM-5) and IncX3 plasmids harboring bla(NDM-4) or bla(NDM-7) were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. In contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring bla(NDM-1), including IncFIB, IncFII, IncL/M, and IncA/C(2), among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of bla(NDM)-harboring plasmids among CPE isolates in Myanmar, contributing to a better understanding of their molecular epidemiology and dissemination in a setting of endemicity.

Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types—IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (

Rationale: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. Patient concerns: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. Diagnosis: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. Interventions: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. Outcomes: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. Lessons: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.

Background Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. Conclusions DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.

Six Klebsiella pneumoniae clinical isolates resistant to various cephalosporins and cephamycins were identified in a Japanese general hospital, a tertiary care hospital, between November 2009 and April 2010. All K. pneumoniae isolates carried blaGES-4 and blaSHV-1, while 2 K. pneumoniae isolates also harbored blaCTX-M-15. The pulsed-field gel electrophoresis patterns revealed that these 6 K. pneumoniae isolates were almost identical, suggesting their clonal relatedness. Plasmid profiles and conjugation assays revealed that these blaGES-4 genes were located on similar conjugative plasmids. These data indicate that nosocomial spread caused by K. pneumoniae isolates producing blaGES-4 carbapenemase occurred at a Japanese general hospital. K. pneumoniae isolate harboring blaGES-4 is rarely reported in Japan, and, to the best of our knowledge, this is the second report of K. pneumoniae isolates harboring blaGES-4 that occurred nosocomial spread in Japan.

Aims Left ventricular diastolic dysfunction (LVDD) has prognostic significance in heart failure (HF). We aimed to assess the impact of LVDD grade stratified by the updated 2016 echocardiographic algorithm (DD2016) on post-discharge outcomes in patients admitted for acute HF and compare with the previous 2009 algorithm (DD2009). Methods and results The study included 481 patients hospitalized for acute decompensated HF. Comprehensive echocardiography and LVDD evaluation were performed just before hospital discharge. The primary endpoint was a composite of cardiovascular death and readmission for HF. The concordance between DD2016 and DD2009 was moderate (κ = 0.44, P Conclusion Despite simplification of the algorithm for LVDD evaluation, the prognostic value of DD2016 for post-discharge cardiovascular events in HF patients was maintained and not compromised in comparison with DD2009.

Background Limited treatment options complicate management of infections with New Delhi metallo-β-lactamase (NDM)-producing organisms. The efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) was assessed against NDM-producing Enterobacteriaceae. Materials and Methods Twelve Escherichia coli clinical isolates harbouring blaNDM-1 and a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT) and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies and whole-genome sequence analysis were used to determine the antimicrobial resistance mechanisms. Results MICs of MEM, ERT and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 µg/mL, respectively. In the checkerboard assay, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared with that of MEM alone. The time-kill study revealed a bactericidal effect in 4 of 13 isolates at 24 h. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination; this was not observed in single antibiotic conditions. Kinetic studies indicated CMZ was a better antagonist for NDM-1 than ERT. Whole-genome sequence analysis did not reveal any explainable differences between isolates susceptible and those non-susceptible to combination therapy. Conclusion In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.

Rationale: Daptomycin (DAP) is a key drug for treating severe Staphylococcus infections. The emergence of DAP non-susceptible Staphylococcus aureus has been widely recognized in clinical situations, although the clinical status of DAP non-susceptible coagulase-negative Staphylococcus (CoNS) infections is unclear. We encountered 2 cases of cardiovascular device infections that were associated with DAP non-susceptible CoNS. Patient concerns: The first case involved a 60-year-old woman with a pump pocket infection in a left ventricular assist device. DAP non-susceptible Staphylococcus capitis subsp. ureolyticus was isolated from a blood culture after treatment using vancomycin (10 days) and DAP (6 days). The second case involved a 71-year-old man with an aortic graft infection. DAP non-susceptible S capitis subsp. ureolyticus was detected in pus after treatment using vancomycin (2 weeks) and DAP (1 week) without complete removal and debridement. Diagnosis: Cardiovascular device infections caused by DAP non-susceptible CoNS. Interventions and outcomes: Whole genome sequencing of these strains revealed multiple mutations in genes that are related to DAP-non-susceptibility in S aureus, which created amino acid substitutions in mprF, dltAB, dltD, rpoC, yycG, cls2, pgsA, and vraSR. To the very best of our knowledge, the substitution patterns were not identical to those previously reported in DAP non-susceptibile S aureus. Lessons: Clinicians should be cautious regarding the emergence of DAP non-susceptible CoNS, especially in cases with implanted prosthetic devices, inadequate debridement, and prior usage of vancomycin and DAP. Further studies are needed to understand the relevance of these genetic changes and DAP-non-susceptibility in CoNS strains.

Background: Although 2-dimensional strain analyses based on speckle tracking echocardiography have been used to detect myocardial deformation, the prognostic impact of 2-dimensional strain is unclear in patients with acute decompensated heart failure (HF). We investigated whether left ventricular and right ventricular (RV) strain parameters assessed by speckle tracking echocardiography provide incremental prognostic information in hospitalized patients because of acute decompensated HF. Methods and Results: Six hundred eighteen patients (age, 72±13 years; 38% women; ejection fraction, 46±16%) hospitalized for acute decompensated HF underwent clinical and echocardiographic evaluation just before discharge. We performed strain analyses of left ventricular global longitudinal strain and left ventricular global circumferential strain. We also analyzed RV longitudinal strain only from the free wall (RV-fwLS) and from all segments of the RV global longitudinal strain wall by using Tomtec software. The primary composite end point was cardiovascular death and readmission for HF. There were 34.8% cardiac events during a median follow-up of 427 days. In multivariate Cox models, among echocardiographic parameters, only impaired RV-fwLS (≥−13.1%; hazard ratio, 1.51; 95% CI, 1.12–2.04; P =0.01) was independently associated with cardiac events. Adding RV-fwLS to clinical risk evaluation (age, New York Heart Association class III/IV, blood urea nitrogen, and brain natriuretic peptide) markedly improved prognostic utility and consequently increased net reclassification improvement by 0.30 ( P =0.01). Conclusions: RV-fwLS is an independent predictor of cardiac events in acute decompensated HF and provides greater prognostic power than standard echocardiographic parameters.

Blood culture is the most critical examination for diagnosing bacterial infections. The longer the blood culture incubation period, the higher the chances of identifying bacterial strains. However, unnecessary extension of the incubation period can burden the capacity of the instrument and merely result in the detection of contaminant bacteria having no clinical significance. This study aimed to optimize the blood culture incubation period using the currently available continuous-monitoring automated blood culture instrument. This was a 2-year retrospective study performed at Osaka University Hospital (January 1, 2016 to December 31, 2017). The BD BACTEC™ FX blood culture system (Becton Dickinson, Sparks, MD, USA) and BD BACTEC™ Plus series blood culture bottles were used. All blood cultures were incubated for more than 12 consecutive days. We reviewed the clinical data of cases that tested positive between 6 and 12 days of incubation. During the study period, 14,822 sets of blood culture were drawn. Of 1751 sets testing positive, 95.7% (1665 sets) became positive within 5 days of incubation. The overall contamination rate (false positives) after 6 days of incubation was 80.2% (69/86 sets). Based on the positive blood culture results, antimicrobials were changed in 7.0% (6/86) of the sets, and a diagnosis of infectious disease was made in only one case. There was no death associated with the extended blood culture results. In conclusion, the clinical impact of extended blood culture incubation for 6 days or more was limited, and a routine extension of the incubation period might be unnecessary.

Background Soluble ST2 (sST2) is a marker of inflammation and fibrosis, which is a significant predictor of prognosis of heart failure (HF), independent of brain natriuretic peptide (BNP). This study aimed to clarify how sST2 associates with clinical outcome through investigations of clinical correlates and mode of death in patients with heart failure with preserved ejection fraction (HFpEF). Methods A total 191 patients with acute decompensated HF and EF ≥50% were prospectively enrolled. Echocardiographic and laboratory data including sST2 were obtained in pre-discharge stable condition. Results Serum sST2 level showed significant positive correlations with C-reactive protein and pentraxin3 levels, and negative correlations with body mass index, albumin, and hemoglobin. Serum sST2 level was significantly higher in patients with all-cause death and non-cardiovascular (CV) death compared to those without events, whereas there was no significant difference in sST2 level between patients with and without CV death. On the other hand, BNP level was significantly higher in patients with all-cause death and CV death compared to those without events. Cox regression analyses adjusted for age and sex revealed that sST2 was a significant predictor of non-CV death, whereas BNP was a significant predictor of CV death. Conclusions Serum sST2 level was associated with non-CV death showing significant correlations with systemic factors including malnutrition and inflammation, while BNP was associated with CV death.

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

Gram-negative fusiform rods were detected in a blood culture obtained from a 63-year-old man who had been hospitalized for a long duration for severe heart failure. Although the organism could not be identified using a conventional method, it was finally identified as a bacterium of the Capnocytophaga ochracea group based on the results of biochemical testing, 16S rRNA sequencing and a matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Although neutropenic patients with poor oral hygiene are exclusively vulnerable to Capnocytophaga bacteremia, this case was unique because such predisposing conditions were not noted. A multi-centered investigation is warranted for a better understanding of this clinically rare, but potentially pathogenic organism.

A 57-year-old woman with severe bronchiectasis frequently received antibiotics, including penicillin, for acute exacerbations due to Pasteurella multocida. Although the bacteria showed a decrease in antibiotic susceptibility, her symptoms and X-ray findings became stable, and severe exacerbations were not observed for the last few years after a low-dose erythromycin treatment was started. The development of a respiratory infection with Pasteurella multocida is relatively uncommon, but it can be controlled by immunomodulation which is associated with long-term macrolide therapy.

Desulfovibrio spp. are sulfate-reducing, anaerobic bacteria that are ubiquitously found in the environment. These organisms infrequently cause human infections, and the clinical characteristics of infection with Desulfovibrio spp. remain unclear. Here, we describe a case of Desulfovibrio desulfuricans bacteremia in an 88-year-old Japanese man with a past medical history of thoracic endovascular aortic repair (TEVAR). His chief complaint was hemoptysis for 2 weeks. A chest contrast-enhanced computed tomography demonstrated an enlarged thoracic aortic aneurysm surrounded by a ring-enhanced lesion, recognized as mediastinal abscess. Gram-negative spiral bacilli were detected in anaerobic blood culture. These bacteria could not be identified using conventional methods, but by analyzing a full base sequence of 16S rDNA, they were identified as D. desulfuricans subsp. desulfuricans. The patient underwent an emergent re-TEVAR, and the infection subsided after being treated with tazobactam/piperacillin and clindamycin, followed by metronidazole. A literature review of previous cases of D. desulfuricans bacteremia suggested that the pathogen was derived from bacterial translocation from the intestine in most cases. Desulfovibrio infection is presumably underestimated due to its infrequency, indolent growth, and difficulty in identification. Desulfovibrio spp. should be suspected when spiral rods are observed in anaerobic culture, and molecular analysis is required for accurate species-level differentiation of the pathogens. To better understand the pathogenicity of these fastidious organisms, further cases based on the exact bacterial identification should be investigated.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced among children in Japan in 2010. There are no long-term multicenter surveillance studies of antimicrobial resistance in S. pneumoniae before and after the introduction of PCV7. Therefore, we examined chronological trends in antimicrobial resistance among 4534 strains of S. pneumoniae isolated from both children and adults in the Kinki region of Japan during 2001–2015. High-level penicillin and third-generation cephalosporin resistance in S. pneumoniae increased among both children and adults during the period before the introduction of PCV7 (2001–2010). Besides penicillin and cephalosporin, pneumococcal carbapenem and macrolide resistance increased among children. The rate of resistance to these antibiotics was higher among children than among adults. The introduction of PCV7 decreased the rate of non-susceptibility to β-lactam antibiotics and the rate of multidrug resistant S. pneumoniae among children, but not among adults.

The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1), IncX3 plasmids harboring blaNDM-4 (n = 2) or blaNDM-7 (n = 1), IncFII plasmids harboring blaNDM-4 (n = 1) or blaNDM-5 (n = 3), and a multireplicon F plasmid harboring blaNDM-5 (n = 1). Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.

Background Identification of carbapenemase-producing Enterobacteriaceae (CPE) in faecal specimens is challenging. This fact is particularly critical because low-level carbapenem-resistant organisms such as IMP-producing CPE are most prevalent in Japan. We developed a modified selective medium more suitable for IMP-type CPE. Methods Fifteen reference CPE strains producing different types of β-lactamases were used to evaluate the commercially available CHROMagar KPC and chromID CARBA as well as the newly prepared MC-ECC medium (CHROMagar ECC supplemented with meropenem, cloxacillin, and ZnSO4) and M-ECC medium (CHROMagar ECC supplemented with meropenem and ZnSO4). A total of 1035 clinical samples were then examined to detect CPE using chromID CARBA and M-ECC medium. Results All tested strains producing NDM-, KPC-, and OXA-48-carbapenemases were successfully cultured in the media employed. Although most of the IMP-positive strains did not grow in CHROMagar KPC, chromID CARBA, or MC-ECC, all tested strains grew on M-ECC. When faecal samples were applied to the media, M-ECC medium allowed the best growth of IMP-type CPE with a significantly higher sensitivity (99.3%) than that of chromID CARBA (13.9%). Conclusions M-ECC medium was determined as the most favourable selective medium for the detection of IMP-type CPE as well as other types of CPE. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2312-1) contains supplementary material, which is available to authorized users.

The objective of the study was to clarify whether controlling nutritional status (CONUT) is useful for predicting the long-term prognosis of patients hospitalized with heart failure (HF). A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (N = 838) were enrolled (298 men, 71.7 ± 13.6 years). At admission, blood samples were collected and nutritional status assessed using CONUT. CONUT scores were defined as follows: 0–1, normal; 2–4, light; 5–8, moderate; and 9–12, severe undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. In the follow-up period [median 541.5 (range 354–786) days], 109 deaths were observed. A Kaplan–Meier analysis revealed that all-cause deaths occurred more frequently in HF patients with nutritional disturbances [n = 93 (26.4%)] than in those with normal nutrition [n = 16 (12.3%); log-rank p

Identifying transmission route of antimicrobial-resistant pathogen is essential for appropriate infection control strategy in healthcare facilities. We report the utility of single-nucleotide variation analysis in tracing nosocomial transmission of antimicrobial-resistant pathogens by describing a pseudo-outbreak case of carbapenem-resistant Klebsiella pneumoniae. The present case highlights that infection control strategy should encompass pathological dissection rooms, neglected but potentially highly contaminated places in hospitals.

Background Overshoot phenomena of the gas exchange ratio (R:VCO2/VO2), ventilatory equivalent for O2 (VE/VO2), and end-tidal O2 pressure (PETO2) are commonly observed during recovery from maximal cardiopulmonary exercise testing (CPX). We investigated the clinical significance of the overshoots of these indices by comparing their magnitudes between healthy subjects and cardiac patients with left ventricular dysfunction. Methods In total, 121 subjects (73 healthy subjects and 48 cardiac patients with left ventricular ejection fraction Results The overshoot phenomena of R, VE/VO2, and PETO2 were observed in all the subjects. The magnitudes of the R (21.4 ± 12.4% vs. 29.3 ± 10.0%, p Conclusions We concluded that the overshoots of R, VE/VO2, and PETO2 during recovery from maximal exercise reflect the natural cardiopulmonary adaptation after exercise and are more prominent in subjects with better cardiopulmonary function.

Clostridium difficile generally causes enterocolitis by producing pathogenic toxins, while extraintestinal infections with C. difficile are extremely rare. Here we report the first documented case of an infective thoracic aortic aneurysm caused by nontoxic C. difficile that occurred after vascular interventions including endovascular aortic repair. The present case illustrates that endovascular interventions may expose patients to the rare infection by yielding the ischemic intestinal tract as an entry site for the pathogen into the bloodstream and providing an anaerobic environment inside the thrombosed aneurysm.

Roseomonas species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of Roseomonas mucosa bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be R. mucosa. The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of Roseomonas bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of Roseomonas bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory. Keywords: Bloodstream infection, Febrile neutropenia, Roseomonas mucosa

We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail.