Dr. Ryuichiro Abe was a clinical doctor majoring in Intensive Care Medicine and Anesthesiology (Certificated in 2019 and 2018, respectively by Japanese Board). Based on the clinical experiences, he decided to be devoted to basic research for bacteriology. His research interests focus on improving the diagnosis of bacterial infection to treat patients more appropriately and preventing the dissemination of antimicrobial drug resistance.
Doctor of Philosophy, Osaka University (2020)
Board Certification, The Japanese Society of Intensive Care Medicine, Intensive Care Medicine (2019)
Board Certification, Japanese Society of Anesthesiologists, Anesthesiology (2018)
Doctor of Medicine, Osaka University (2011)
Samuel Yang, Postdoctoral Faculty Sponsor
Effects of Ventilatory Settings on Pendelluft Phenomenon During Mechanical Ventilation
2021; 66 (1): 1-10
Pendelluft phenomenon is defined as the displacement of gas from a more recruited nondependent (ND) lung region to a less recruited dependent (D) lung region. This phenomenon may cause lung injury. Thus, a lung model for pendelluft was established, and the effects of ventilatory settings on pendelluft were examined.Two sets of the twin-bellows-type training test lung (TTL) model were utilized. One set of bellows simulated the diaphragm, and the other simulated the lung. One TTL model represented the ND region, and the other represented the D region. The lung bellows were connected to each other and were ventilated with 1 ventilator. The diaphragm bellows were ventilated with 2 synchronized ventilators that regulated pleural pressure levels. We simulated pendelluft by applying different pleural pressure levels to the D and ND bellows. The increment of the tidal volume in the D region from the "no breathing effort" condition was defined as the pendelluft volume. The effects of ventilator settings, such as ventilatory modes, triggering sensitivity, inspiratory pressurization, and inspiratory cycling-off, were examined. The changes in tidal volumes in the D region based on the control settings were compared to assess the severity of pendelluft.The gas flow from the D region to the ND region was found to be essential in pendelluft, but the severity of this phenomenon was not always proportional to gas flows. The severity increased with the increase in the differences in pleural pressure levels between the ND and D regions, and it was amplified by the difference in lung mechanics between the ND and D regions. However, the ventilator settings had minimal effect on the severity of pendelluft.The pendelluft was affected by the heterogeneity of lung mechanics and pleural pressure. Furthermore, a minimal association was observed between the ventilator settings and the severity of pendelluft.
View details for DOI 10.4187/respcare.07880
View details for Web of Science ID 000614253400002
View details for PubMedID 32900913
Enhanced Carbapenem Resistance through Multimerization of Plasmids Carrying Carbapenemase Genes.
The worldwide dissemination of carbapenem-resistant Enterobacteriaceae (CRE) poses a critical human health issue by limiting the range of antibiotics that are usable in the treatment of common bacterial infections. Along with CRE, carbapenem heteroresistance has disseminated worldwide, which is described as different levels of carbapenem resistance within a seemingly isogenic bacterial population. Unstable carbapenem resistance will likely lead to unexpected treatment failure due to the enhanced resistance after initiation of treatment, contradicting antimicrobial susceptibility test results. Porin mutation and tandem amplification of the carbapenemase gene have been reported as mechanisms underlying enhanced carbapenem resistance. In this study, we identified multimerization of plasmids carrying carbapenemase genes, by using Southern blotting, whole-genome sequencing, and quantitative PCR (qPCR) analysis for the CRE isolates obtained in our previous surveillance in Osaka, Japan. Plasmids harboring a carbapenemase gene were multimerized by recA, likely through recombination at two consecutive sets of transposase genes of the IS91 family, thereby producing various plasmids of discrete sizes in a single bacterial cell of an Escherichia coli isolate. This multimerization resulted in increased copy numbers of carbapenemase genes, leading to enhanced gene transcription as well as carbapenem resistance. Prior exposure to meropenem further increased the copy number of carbapenemase genes, readily resulting in enhancement of carbapenem resistance. This mechanism may lead to clinical treatment failure by sifting antimicrobial resistance after the treatment initiation. IMPORTANCE We demonstrated the multimerization of plasmids harboring carbapenemase genes, and multimeric plasmids of various discrete sizes existed in a host bacterial cell of Escherichia coli. Plasmid multimerization along with increased copy numbers of carbapenemase genes resulted in enhanced carbapenemase resistance, which was readily accelerated by an overnight preexposure to meropenem. This mechanism may lead to treatment failure in clinical settings after the initiation of antimicrobial therapy.
View details for DOI 10.1128/mBio.00186-21
View details for PubMedID 34154401
Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant Enterobacteriaceae
2020; 5 (6)
Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6 For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments.IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.
View details for DOI 10.1128/mSystems.00759-20
View details for Web of Science ID 000630974900001
View details for PubMedID 33172969
View details for PubMedCentralID PMC7657596
Genomic characterisation of a novel plasmid carrying bla IMP-6 of carbapenem-resistant Klebsiella pneumoniae isolated in Osaka, Japan
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
2020; 21: 195-199
To analyse plasmids carrying blaIMP-6 in Klebsiella pneumoniae isolates obtained from multicentre carbapenem-resistant Enterobacteriaceae surveillance.Plasmids harbouring blaIMP-6 were characterised by the whole-genome sequencing of four Klebsiella pneumoniae isolates carrying blaIMP-6, and compared with the pKPI-6 plasmid, which is widespread in western Japan, through pulsed-field gel electrophoresis, Southern blotting, bacterial conjugation, and qPCR.Whole-genome sequencing analysis revealed that three of the four isolates carried approximately 50 kbp plasmids similar to the pKPI-6 plasmid; however, one isolate carried a 250 kbp plasmid harbouring blaIMP-6 (pE196_IMP6). So far, all of the reported plasmids carrying blaIMP-6 were similar to the pKPI-6 plasmid, and this plasmid was a novel blaIMP6-carrier. The size and transferability of this plasmid was confirmed by Southern hybridisation and conjugation experiments. It was demonstrated that the generation of plasmid pE196_IMP6 was due to an intramolecular transposition mediated by IS26, and a homologous recombination between plasmids pKPI-6 and pE013 that was obtained from another carbapenem-resistant Enterobacteriaceae isolate in this analysis. As a result of co-integration with pE013, pE196_IMP6 acquired six additional pairs of type II toxin-antitoxin systems that pKPI-6 does not carry. Transcription of all of the toxin-antitoxin systems were confirmed in an isolate carrying pE196_IMP6 by qPCR.This study detected a novel plasmid carrying blaIMP-6, and revealed the origin of this plasmid. Toxin-antitoxin system acquisition could enable pE196_IMP6 maintenance persistently through successions, even without selection pressure by the clinical usage of antimicrobials, generating broad dissemination and longer carbapenem-resistant Enterobacteriaceae colonisation duration in patients.
View details for DOI 10.1016/j.jgar.2019.10.003
View details for Web of Science ID 000544879300036
View details for PubMedID 31627024
In Vitro Efficacy of Meropenem-Cefmetazole Combination Therapy against New Delhi Metallo-beta-lactamase-producing Enterobacteriaceae
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
2020; 55 (3): 105905
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.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.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.In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.
View details for DOI 10.1016/j.ijantimicag.2020.105905
View details for Web of Science ID 000518855500021
View details for PubMedID 31991221
Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant Enterobacteriaceae.
BMC research notes
2019; 12 (1): 740
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates).Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.
View details for DOI 10.1186/s13104-019-4779-x
View details for PubMedID 31706328
View details for PubMedCentralID PMC6842521
First Identification and genomic characterization of multidrug-resistant carbapenemase-producing Enterobacteriaceae clinical isolates in Malawi, Africa
JOURNAL OF MEDICAL MICROBIOLOGY
2019; 68 (12): 1707-1715
Purpose. Carbapenemase-producing Enterobacteriaceae (CPE) have become a global concern and a serious threat to human health due to their resistance to multiple antibiotics. In this study, we identified and characterized CPE for the first time in Malawi, southeastern Africa.Methodology. We investigated the possible presence of carbapenemases among a collection of 200 ceftriaxone-nonsusceptible Gram-negative clinical isolates obtained from five Malawian hospitals between January 2016 and December 2017, using both phenotypic and genotypic tests. Molecular typing of CPE was done by PFGE, multilocus sequence typing (ST) or phylogenetic grouping. Resistant plasmids were characterized by S1 PFGE, Southern blotting and conjugation assays.Results. Out of 200 isolates, we detected 16 (8 %) CPE of which all originated from one referral hospital, Kamuzu Central Hospital, in the Central part of Malawi. Of 16 isolates, seven Klebsiella pneumoniae ST340/CC258 carried blaKPC-2, two Escherichia coli ST636 (phylogroup B2) carried blaNDM-5, six E. coli ST617 (phylogroup A) and one Klebsiella variicola carried blaOXA-48. All carbapenemases were plasmid-encoded, but only blaNDM-5-carrying plasmids could be conjugated. Most isolates co-harboured other β-lactamases and consequently exhibited a wider spectrum of resistance to commonly used antibiotics. We observed indistinguishable genetic profiles between strain types, despite originating from different wards, suggesting acquisition during admission and intra-hospital spread.Conclusion. This report strongly suggests a probable existence of highly resistant various types of CPE organisms in Malawi including KPC-2-producing K. pneumoniae ST340/CC258, a known high-risk epidemic lineage.
View details for DOI 10.1099/jmm.0.001087
View details for Web of Science ID 000500776700003
View details for PubMedID 31661049
Perioperative Enteral Nutrition After Left Ventricular Assist Device Implantation
NUTRITION AND METABOLIC INSIGHTS
2018; 11: 1178638818810393
We assessed what predicts nutritional adequacy at day 14 following implantation of left ventricular assist device (LVAD).We retrospectively reviewed the cases of 97 adult patients who underwent LVAD implantation at our institution from June 2011 to June 2016. We divided the patients into two groups based on the administered enteral nutrition (EN) calories on post-operative day (POD) 14: the EN calories of group SEN (sufficient enteral nutrition) were >80% of their total target calories, or the EN calories of group IEN (insufficient enteral nutrition) were <80% of their total target calories. We compared the two groups in terms of the perioperative factors within 1 week after surgery.Groups SEN and IEN consisted of 53 and 44 patients, respectively. The mean doses of adrenaline and noradrenaline, mean central venous pressure (CVP), duration of nitric oxide administration, and mean residual gastric volume during 1 week after surgery in group SEN were significantly lower than those in group IEN (P < .05). In multivariate analysis, higher CVP during 1 week after surgery was identified as an independent risk factor for delayed EN on POD14 (odds ratio, 1.40; 95% confidence interval, 1.11-1.66; P = .0037). Total bilirubin, occurrence of acute kidney injury, and mixed venous blood saturation during 1 week after surgery were not significant predictors for EN on POD14.Increased CVP within 1 week after LVAD implantation was an independent factor for reduced EN feeding.
View details for DOI 10.1177/1178638818810393
View details for Web of Science ID 000454842100001
View details for PubMedID 30479486
View details for PubMedCentralID PMC6243400
Factors Related to the Severity of Early Postoperative Infection After Heart Transplantation in Patients Surviving Prolonged Mechanical Support Periods: Experience at a Single University
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
2018; 32 (1): 53-59
The authors examined the effect of prolonged support with continuous-flow ventricular assist devices (CF-VADs) and other related factors on the severity of infections within 30 days of heart transplantation (HTx).A retrospective analysis of consecutive HTx procedures.University hospital, between 2010 and 2016.A cohort of 53 heart transplantation recipients (median age, 38.5 yr; interquartile range [IQR], 30.3-49.2 yr; women, 34%).Forty-nine patients required CF-VAD support (median duration, 946 d; IQR, 600-1,132 d).Severity of postoperative infections was categorized as follows: no infection, minor infection (resolved within 14 days), major infection (resolved after >14 days), and severe infection (septic shock). Results were expressed as number (frequency) and median with IQR. Potential risk factors for increased infection severity were expressed as odds ratio (OR) with 95% confidence interval (CI). Postoperatively, no infection, minor infection, major infection, and severe infection occurred in 32 (60.4%), 8 (15.1%), 8 (15.1%), and 5 patients (9.4%), respectively. Active ventricular assist device (VAD)-specific infections at the time of HTx occurred in 37.7% of patients. Moderate-to-severe primary graft dysfunction occurred in 26.4% of the patients. Multivariable analysis indicated that risk factors for increased infection severity included active VAD-specific infection (OR 4.8; 95% CI 2.3-11.2) and moderate-to-severe primary graft dysfunction (OR 8.8; 95% CI 2.1-42.5) but not duration of CF-VAD support (OR 1.0; 95% CI 1.0-1.0).Active VAD-specific infection and poor graft function likely contribute to the severity of early postoperative infections after HTx.
View details for DOI 10.1053/j.jvca.2017.07.004
View details for Web of Science ID 000424730300008
View details for PubMedID 29229257
Right ventricular functional assessment by three-dimensional transesophageal echocardiography is useful for withdrawal from a right ventricular assist device: a case report
JA CLINICAL REPORTS
2017; 3: 40
Right ventricular assist device (RVAD) implantation is one type of surgical treatment used for right heart failure. It is important to assess right ventricular (RV) function precisely when RVAD withdrawal is considered. Although assessment of RV function is difficult due to its complicated shape and contraction pattern, the volumetric analysis method of three-dimensional (3D) transesophageal echocardiography (TEE) has been developed and is useful for this task. We report the case of a 79-year-old man who successfully underwent RVAD withdrawal and evaluation using 3D TEE. 3D TEE had an important role in determining the timing of withdrawal from RVAD in this case.
View details for DOI 10.1186/s40981-017-0112-7
View details for Web of Science ID 000407775200001
View details for PubMedID 29457084
View details for PubMedCentralID PMC5804624
[Comparison of Aortic Valve Replacement Combined with Coronary Artery Bypass Grafting and Transcatheter Aortic Valve Implantation Combined with Off-pump Coronary Artery Bypass Grafting].
Masui. The Japanese journal of anesthesiology
2017; 66 (4): 370-375
The purpose of this study was to compare the perioperative management of aortic valve replacement combined with coronary artery bypass grafting (AVR+CABG) and transcatheter aortic valve implantation combined with off-pump coronary artery bypass grafting (TAVI+OPCAB).A retrospective analysis was performed on patients who had undergone either AVR+CABG or TAVI+OPCAB for AS and CAD in Osaka Univer- sity Medical Hospital from January to October, 2014.AVR+CABG was performed in 11 pa- tients (group A) and TAVI+OPCAB was performed in 4 patients (group T) in this period. The patients in group T was significantly older than the patients in group A. There were no significant differences in other background factors. Procedure time and postoperative mechanical ventilation time were shorter in group T than in group A. Postoperative recovery was signifi- cantly faster in group T than in group A.TAVI+OPCAB is less invasive than AVR+CABG and an effective treatment for high risk patient with AS and CAD.
View details for PubMedID 30382634