研究者業績
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  2. 荒川 宜親

荒川 宜親

アラカワ ヨシチカ  (Yoshichika Arakawa)

基本情報

所属
藤田医科大学 医学部微生物学 客員教授
金城学院大学 薬学部 客員教授
名古屋大学 名古屋大学 医学部／大学院医学系研究科 招へい教員（非常勤講師）
厚生労働省 国立感染症研究所 元部長 名誉所員
東海国立大学機構 名古屋大学 名誉教授
学位
医学博士(1989年3月 名古屋大学)
研究者番号
10212622
J-GLOBAL ID
201101032201306103
Researcher ID
P-5997-2015
researchmap会員ID
6000030043

In the 1980s, I initiated the analyses of a chromosomal genetic region (cps cluster) that is responsible for biosynthesis of K2 capsular polysaccharide in Klebsiella pneumoniae strain Chedid, as well as the characterization of chromosomally encoded β‐lactamase LEN-1 of K. pneumoniae strain LEN-1.  My collaborators and I firstly succeeded in the expression of K2 capsular polysaccharide of strain Chedis in an Escherichia coli K12 by introduction of an about 24-kb chromosomal DNA fragment of Chedid.   We also found that several regulatory proteins, chromosomal RcsA and RcsB, as well as plasmid mediated RmpA2, were involved in the expression of the cps clusters of K. pneumoniae Chedid.

   As for the characterization of β‐lactamase LEN-1 produced by  K. pneumoniae strain LEN-1, we found that the amino acid sequence of LEN-1 showed a very high similarity to the R‐plasmid‐mediated penicillinase TEM‐1 on the amino acid sequence level, and this strongly suggested the origination of TEM‐1 from the chromosomal penicillinases of K. pneumoniae or related bacteria.  

   Moreover, the chromosomal KOXY β‐lactamase (or K1 β‐lactamase) of Klebsiella oxytoca was found to belong to the class A β‐lactamases that include LEN‐1 and TEM‐1, although KOXY can effectively hydrolyze cefoperazone (CPZ) like the chromosomal AmpC type cephalosporinases of various Enterobacteriaceae that can hydrolyze several cephalosporins including CPZ.

   Furthermore, my collaborators and I found plural novel serine‐type β‐lactamases, such as MOX‐1, SHV‐24, TEM‐91, CTX‐M‐64, CMY‐9, CMY‐19, GES‐3, GES‐4, and TLA‐3, mediated by plasmids. Besides these serine‐type β‐lactamases, we also first identified exogenously acquired metallo‐β‐lactamases (MBLs), IMP‐1 and SMB‐1, in imipenem‐resistant Serratia marcescens, and the IMP‐1‐producing S. marcescens TN9106 became the index case for carbapenemase‐producing Enterobacteriaceae (CPE). I developed the sodium mercaptoacetic acid (SMA)‐disk test for the simple identification of MBL‐producing bacteria. We were also the first to identify a variety of plasmid‐mediated 16S ribosomal RNA methyltransferases, RmtA, RmtB, RmtC, and NpmA, from various Gram‐negative bacteria that showed very high levels of resistance to a wide range of aminoglycosides. Furthermore, we first found plasmid‐mediated quinolone efflux pump (QepA) and fosfomycin‐inactivating enzymes, e.g., plasmid-mediated FosA3 of E. coli and chromosomally-encoded FosK in Acinetobacter soli.

   We also characterized the penicillin-reduced susceptible Streptococcus agalactiae (PRGBS) for the first time, together with macrolide‐resistant Mycoplasma pneumoniae, Campylobacter jejuni, and Helicobacter pylori, as well as carbapenem‐resistant Haemophilus influenzae.

   At present, my research group is involved with the researches and developments of inhibitors for MBLs and serine-type carbapenemases to overcome the urgent AMR issues by the support of AMED (Japan Agency for Medical Research and Development).

研究キーワード

 2

研究分野

 3

主要な経歴

 29
もっとみる

学歴

 3

委員歴

 28
もっとみる

受賞

 3

論文

 296
  • Yusuke Ohsaki, Wataru Hayashi, Satomi Saito, Shunsuke Osaka, Yui Taniguchi, Shota Koide, Kumiko Kawamura, Yukiko Nagano, Yoshichika Arakawa, Noriyuki Nagano
    JAPANESE JOURNAL OF INFECTIOUS DISEASES 70(5) 590-592 2017年9月  
    Global spread of the plasmid-mediated colistin resistance gene, mcr-1 poses a challenge to public health because colistin is the last-line-of-defense against severe infections of multidrug-resistant Gram-negative bacteria. In Japan, a few studies have reported the prevalence of mcr-1 among food animal-derived Escherichia coli isolates, but the prevalence of mcr-1 in retail meats is not well known. We report here the first detection of mcr-1 in retail chicken meat. A total of 70 extended-spectrum betalactamase-producing E. coli isolates, recovered from retail chicken meats between August 2015 and June 2016, were screened for mcr-1. We found 1 CTX-M-1 beta-lactamase-producing E. coli isolate belonging to ST1684, phylogroup A. The mcr-1 gene was not located on an Inch plasmid encoding the bla(CTX-M-1) gene. However, whole plasmid sequencing revealed that mcr-1 was located on an IncI2 plasmid. The sequences of the nikB-mcr-1-pap2-ydfA-topB region of the IncI2 plasmid in this study was almost identical to that of the previously described IncI2 plasmid, pECJS-61-63 present in E. coli isolated from pig feces in China, except for containing a synonymous mutation in the mcr-1 gene. Plasmid carrying the mcr-1 gene have not yet been identified in human isolates in Japan. Thus, strict monitoring or surveillance of colistin resistance among Gram-negative bacteria recovered from retail meat of food animals under colistin pressure, and humans, is crucial.
  • Hirotsugu Banno, Kouji Kimura, Yosuke Tanaka, Tsuyoshi Sekizuka, Makoto Kuroda, Wanchun Jin, Jun-ichi Wachino, Keiko Yamada, Keigo Shibayama, Yoshichika Arakawa
    PLOS ONE 12(8) 2017年8月  
    Group B streptococci (GBS; Streptococcus agalactiae) are the leading cause of neonatal invasive diseases and are also important pathogens for elderly adults. Until now, nearly all GBS with reduced penicillin susceptibility (PRGBS) have shown beta-hemolytic activity and grow on sheep blood agar. However, we have previously reported three PRGBS clinical isolates harboring a CylK deletion that form small less hemolytic colonies. In this study, we examined the causes of small, less hemolytic colony formation in these clinical isolates. Isogenic strains were sequenced to identify the mutation related to a small colony size. We identified a 276_277insG nucleic acid insertion in the thiamin pyrophosphokinase (tpk) gene, resulting in premature termination at amino acid 103 in TPK, as a candidate mutation responsible for small colony formation. The recombinant strain Delta tpk, which harbored the 276_277insG insertion in the tpk gene, showed small colony formation. The recombinant strain.cylK, which harbored the G379T substitution in cylK, showed a reduction in hemolytic activity. The phenotypes of both recombinant strains were complemented by the expression of intact TPK or CylK, respectively. Moreover, the use of Rapid ID 32 API and VITEK MS to identify strains as GBS was evaluated clinical isolates and recombinant strains. VITEK MS, but not Rapid ID 32 API, was able to accurately identify the strains as GBS. In conclusion, we determined that mutations in tpk and cylK caused small colonies and reduced hemolytic activity, respectively, and characterized the clinical isolates in detail.
  • Chihiro Norizuki, Jun-ichi Wachino, Masahiro Suzuki, Kumiko Kawamura, Noriyuki Nagano, Kouji Kimura, Yoshichika Arakawa
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 61(6) 2017年6月  
    We investigated the genetic backbones of 14 bla(CTX-M-8)-positive Escherichia coli isolates recovered from human stool samples and chicken meat. All isolates carried IncI1 plasmids with bla(CTX-M-8) (bla(CTX-M-8)/IncI1), and most (9/14) belonged to a specific genetic lineage, namely, plasmid sequence type 113 (pST113). The genetic contexts of the nine bla(CTX-M-8)/IncI1 pST113 plasmids were similar, regardless of the source. These results suggest the probable local transfer of bla(CTX-M-8)/IncI1 between humans and chickens with genetically diverse E. coli.
  • Satomi Saito, Yoshio Koori, Yusuke Ohsakil, Shunsuke Osaka, Kozue Anal, Yukiko Nagano, Yoshichika Arakawa, Noriyuki Nagano
    JAPANESE JOURNAL OF INFECTIOUS DISEASES 70(3) 301-304 2017年5月  
    beta-lactamase genes were detected and characterized from 10 non-typhoidal Salmonella (NTS) clinical isolates resistant to third-generation cephalosporins collected between 2012 and 2014 in Japan. Five strains showed cefotaxime minimum inhibitory concentration (MIC) >= 64 mu g/ml and positive clavulanic acid inhibition results. The bla(CTX-M-2) was detected in 3 strains (serotypes Stanley and Muenchen), whereas bla(TEM-52) (serotype Manhattan) and bla(SHV-12) (serotype Infantis) were each found in 1 strain. bla(CMY-2) was detected in the remaining 5 strains (serotypes Infantis, Rissen, Newport, and Saintpaul) with cefotaxime MICs of 4-32 mu g/ml and positive cloxacillin-and 3-aminophenylboronic acid -based inhibition tests. ISEcp1 was located upstream of the bla(CMY-2) in 4 strains and of the bla(CTX-M-2). in 1 strain. Incompatibility (Inc)A/C, IncP, and IncIl plasmids were present in the strains harboring bla(CMY-2), which were detected predominantly in this study. Acquisition of resistance to third-generation cephalosporins by invasive NTS may limit therapeutic options for severe systemic infections and causing serious public health problems. Though such resistant clinical isolates are still rare in Salmonella species in Japan, our findings reveal the presence of cephem-resistant NTS in food handlers, thus emphasizing the necessity of more systematic nationwide investigations.
  • Yukihiro Hiramatsu, Yusuke Miyaji, Nao Otsuka, Yoshichika Arakawa, Keigo Shibayama, Kazunari Kamachi
    EMERGING INFECTIOUS DISEASES 23(4) 699-701 2017年4月  
    Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014-2016 (8%) was significantly lower than the frequency in 2005-2007 (41%), 2008-2010 (35%), and 2011-2013 (25%). This reduction was closely associated with changes in genotypes.
  • Rina Taniguchi, Kouji Kimura, Akira Miyazaki, Hirotsugu Banno, Wanchun Jin, Keiko Yamada, Jun-ichi Wachino, Yoshichika Arakawa
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 72(3) 941-942 2017年3月  
  • X. -L. Cao, H. Shen, Y. -Y. Xu, X. -J. Xu, Z. -F. Zhang, L. Cheng, J. -H. Chen, Y. Arakawa
    EPIDEMIOLOGY AND INFECTION 145(4) 818-824 2017年3月  
    Fosfomycin has become a therapeutic option in urinary tract infections. We identified 57 fosfomycin-resistant Escherichia coli from 465 urine-derived extended-spectrum beta-lactamase (ESBL)-producing isolates from a Chinese hospital during 2010-2014. Of the 57 fosfomycinresistant isolates, 51 (89.5%) carried fosA3, and one carried fosA1. Divergent pulsed-field gel electrophoresis profiles and multi-locus sequence typing results revealed high clonal diversity in the fosA3-positive isolates. Conjugation experiments showed that the fosA3 genes from 50 isolates were transferable, with IncFII or IncI1 being the most prevalent types of plasmids. The high prevalence of fosA3 was closely associated with that of bla(CTX-M). Horizontal transfer, rather than clonal expansion, might play a central role in dissemination. Such strains may constitute an important reservoir of fosA3 and bla(CTX-M), which may well be readily disseminated to other potential human pathogens. Since most ESBL-producing E. coli have acquired resistance to fluoroquinolones worldwide, further spread of fosA3 in such E. coli isolates should be monitored closely.
  • M. Hayashi, K. Kawamura, M. Matsui, M. Suzuki, S. Suzuki, K. Shibayama, Y. Arakawa
    JOURNAL OF HOSPITAL INFECTION 95(3) 318-323 2017年3月  
    Background: Nosocomial infections caused by Acinetobacter baumannii international clone II (IC II) can cause severe clinical outcomes. Aim: Differential evaluation of bactericidal efficacy of chlorhexidine gluconate (CHX) and benzethonium chloride (BZT) disinfectants against IC II and non-IC II isolates. Methods: Minimum inhibitory concentrations (MICs) of CHX and BZT were determined for 137 A. baumannii IC II, 99 non-IC II and 69 non-baumannii isolates, further classified according to MIC values into disinfectant-reduced susceptible (DRS) and disinfectantsusceptible (DS) groups. Time-kill curves and minimum bactericidal concentrations (MBCs) were evaluated for representative isolates in each group. Results: CHX and BZT MIC(90)s for IC II isolates were 100 and 175 mg/L, respectively, but those for non-IC II and non-baumannii isolates were < 100 mg/L. Nevertheless, time-kill curves indicated that CHX and BZT reduced live bacterial cell number by 5 log(10) for IC II and non-IC II isolates within 30 s when used at 1000 mg/L, comparable to practical use concentrations. CHX MBC at 30 s was 1000 mg/L for IC II and non-IC II isolates, and was not influenced by addition of 3% bovine serum albumin (BSA); BZT MBC at 30 s was 100 mg/L without BSA and increased up to 500 mg/L upon addition of BSA. No significant differences in BSA were found between DRS and DS isolates. Conclusion: CHX and BZT were effective against Acinetobacter spp. including IC II at a concentration of 1000 mg/L and exposure for at least 30 s, but their concentrations should be considered carefully to ensure sufficient effects in both clinical and healthcare settings.(C) 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
  • Kato K, Mizumoto H, Matsubara K, Hata A, Wachino JI, Arakawa Y, Hata D
    Idcases 10 135-137 2017年  
  • Masato Inaba, Naoyuki Matsuda, Hirotsugu Banno, Wanchun Jin, Jun-ichi Wachino, Keiko Yamada, Kouji Kimura, Yoshichika Arakawa
    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 48(6) 680-689 2016年12月  
    The host stress hormone norepinephrine (NE), also called noradrenaline, is reported to augment bacterial growth and pathogenicity, but few studies have focused on the effect of NE on the activity of antimicrobials. The aim of this study was to clarify whether NE affects antimicrobial activity against multidrug-resistant Acinetobacter baumannii (MDR-AB). Time-kill studies of tigecycline (TIG) and colistin (COL) against MDR-AB as well as assays for factors contributing to antibiotic resistance were performed using MDR-AB clinical strains both in the presence and absence of 10 mu M NE. In addition, expression of three efflux pump genes (adeB, adeJ and adeG) in the presence and absence of NE was analysed by quantitative reverse transcription PCR. Viable bacterial cell counts in TIG-supplemented medium containing NE were significantly increased compared with those in medium without NE. In contrast, NE had little influence on viable bacterial cell counts in the presence of COL. NE-supplemented medium resulted in an ca. 2 log increase in growth and in bacterial cell numbers adhering on polyurethane, silicone and polyvinylchloride surfaces. Amounts of biofilm in the presence of NE were ca. 3-fold higher than without NE. Expression of the adeG gene was upregulated 4-6-fold in the presence of NE. In conclusion, NE augmented factors contributing to antibiotic resistance and markedly reduced the in vitro antibacterial activity of TIG against MDR-AB. These findings suggest that NE treatment may contribute to the failure of TIG therapy in patients with MDR-AB infections. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
  • Shinako Fukigai, Makiko Morimoto, Kouji Kimura, Yo Doyama, Akira Miyazaki, Chitose Kamiya, Hirotsugu Banno, Eriko Morishima, Tomohiro Onoda, Noriyuki Nagano, Wanchun Jin, Jun-ichi Wachino, Keiko Yamada, Yoshichika Arakawa
    DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE 85(3) 309-312 2016年7月  
    We evaluated the feasibility and efficacy of a commercially available methicillin-resistant Staphylococcus aureus (MRSA)-selective agar, chromID (TM) MRSA, to detect group B streptococci with reduced penicillin susceptibility (PRGBS) in this study. The results showed 72.4% (21/29) sensitivity and 98.4% (60/61) specificity to detect PRGBS using this method. (C) 2016 Elsevier Inc. All rights reserved
  • Jun-ichi Wachino, Yoshihiro Yamaguchi, Shigetarou Mori, Wanchun Jin, Kouji Kimura, Hiromasa Kurosaki, Yoshichika Arakawa
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 60(7) 4274-4282 2016年7月  
    Metallo-beta-lactamases (MBLs) confer resistance to carbapenems, and their increasing global prevalence is a growing clinical concern. To elucidate the mechanisms by which these enzymes recognize and hydrolyze carbapenems, we solved 1.4 to 1.6 angstrom crystal structures of SMB-1 (Serratia metallo-beta-lactamase 1), a subclass B3 MBL, bound to hydrolyzed carbapenems (doripenem, meropenem, and imipenem). In these structures, SMB-1 interacts mainly with the carbapenem core structure via elements in the active site, including a zinc ion (Zn-2), Q157[113] (where the position in the SMB-1 sequence is in brackets after the BBL number), S221[175], and T223[177]. There is less contact with the carbapenem R2 side chains, strongly indicating that SMB-1 primarily recognizes the carbapenem core structure. This is the first report describing how a subclass B3 MBL recognizes carbapenems. We also solved the crystal structure of SMB-1 in complex with the approved drugs captopril, an inhibitor of the angiotensin-converting enzyme, and 2-mercaptoethanesulfonate, a chemoprotectant. These drugs are inhibitors of SMB-1 with K-i values of 8.9 and 184 mu M, respectively. Like carbapenems, these inhibitors interact with Q157[113] and T223[177] and their thiol groups coordinate the zinc ions in the active site. Taken together, the data indicate that Q157[113], S221[175], T223[177], and the two zinc ions in the active site are key targets in the design of SMB-1 inhibitors with enhanced affinity. The structural data provide a solid foundation for the development of effective inhibitors that would overcome the carbapenem resistance of MBL-producing multidrug-resistant microbes.
  • Yohei Doi, Jun-ichi Wachino, Yoshichika Arakawa
    INFECTIOUS DISEASE CLINICS OF NORTH AMERICA 30(2) 523-+ 2016年6月  
    Aminoglycoside-producing Actinobacteria are known to protect themselves from their own aminoglycoside metabolites by producing 16S ribosomal RNA methyltransferase (16S-RMTase), which prevents them from binding to the 16S rRNA targets. Ten acquired 16S-RMTases have been reported from gram-negative pathogens. Most of them posttranscriptionally methylate residue G1405 of 16S rRNA resulting in high-level resistance to gentamicin, tobramycin, amikacin, and plazomicin. Strains that produce 16S-RMTase are frequently multidrug-resistant or even extensively drug resistant. Although the direct clinical impact of high-level aminoglycoside resistance resulting from production of 16S-RMTase is yet to be determined, ongoing spread of this mechanism will further limit treatment options for multidrug-resistant and extensively drug-resistant gram-negative infections.
  • Nao Otsuka, Kensei Gotoh, Naoko Nishimura, Takao Ozaki, Yukitsugu Nakamura, Kiyohito Haga, Makoto Yamazaki, Fumio Gondaira, Kenji Okada, Yusuke Miyaji, Hiromi Toyoizumi-Ajisaka, Keigo Shibayama, Yoshichika Arakawa, Kazunari Kamachi
    MICROBIOLOGY AND IMMUNOLOGY 60(5) 326-333 2016年5月  
    An ELISA that measures anti-PT IgG antibody has been used widely for the serodiagnosis of pertussis; however, the IgG-based ELISA is inadequate for patients during the acute phase of the disease because of the slow response of anti-PT IgG antibodies. To solve this problem, we developed a novel IgM-capture ELISA that measures serum anti-Bordetella pertussis Vag8 IgM levels for the accurate and early diagnosis of pertussis. First, we confirmed that Vag8 was highly expressed in all B. pertussis isolates tested (n = 30), but little or none in other Bordetella species, and that DTaP vaccines did not induce anti-Vag8 IgG antibodies in mice (i.e. the antibody level could be unaffected by the vaccination). To determine the immune response to Vag8 in B. pertussis infection, anti-Vag8 IgM levels were compared between 38 patients (acute phase of pertussis) and 29 healthy individuals using the anti-Vag8 IgM-capture ELISA. The results revealed that the anti-Vag8 IgM levels were significantly higher in the patients compared with the healthy individuals (P < 0.001). ROC analysis also showed that the anti-Vag8 IgM-capture ELISA has higher diagnostic accuracy (AUC, 0.92) than a commercial anti-PT IgG ELISA kit. Moreover, it was shown that anti-Vag8 IgM antibodies were induced earlier than anti-PT IgG antibodies on sequential patients' sera. These data indicate that our novel anti-Vag8 IgM-capture ELISA is a potentially useful tool for making the accurate and early diagnosis of B. pertussis infection.
  • Hiroe Ohno, Jun-ichi Wachino, Ryoichi Saito, Wanchun Jin, Keiko Yamada, Kouji Kimura, Yoshichika Arakawa
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 60(4) 2580-2581 2016年4月  
  • Kunihiko Nakane, Kumiko Kawamura, Kensuke Goto, Yoshichika Arakawa
    APPLIED AND ENVIRONMENTAL MICROBIOLOGY 82(6) 1818-1827 2016年3月  
    The actual state of intestinal long-term colonization by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in healthy Japanese people remains unclear. Therefore, a total of 4,314 fecal samples were collected from 2,563 food handlers from January 2010 to December 2011. Approximately 0.1 g of each fecal sample was inoculated onto a MacConkey agar plate containing cefotaxime (1 mu g/ml). The bacterial colonies that grew on each plate were checked for ESBL production by the double-disk synergy test, as recommended by the Clinical and Laboratory Standards Institute. The bacterial serotype, antimicrobial susceptibility, pulsotype, sequence type (ST), and ESBL genotype were checked, and the replicon types of plasmids harboring the ESBL gene were also determined after conjugation experiments. ESBL producers were recovered from 70 (3.1%) of 2,230 participants who were checked only once. On the other hand, ESBL producers were isolated at least once from 52 (15.6%) of 333 participants who were checked more than twice, and 13 of the 52 participants carried ESBL producers for from more than 3 months to up to 2 years. Fluoroquinolone (FQ)-resistant E. coli strains harboring bla(CTX-M) were repeatedly recovered from 11 of the 13 carriers of blaCTX-M-harboring E. coli. A genetically related FQ-resistant E. coli O25b: H4-ST131 isolate harboring bla(CTX-M-27) was recovered from 4 of the 13 carriers for more than 6 months. Three FQ-resistant E. coli O1: H6-ST648 isolates that harbored bla(CTX-M-15) or bla(CTX-M-14) were recovered from 3 carriers. Moreover, multiple CTX-M-14-or CTX-M-15-producing E. coli isolates with different serotypes were recovered from 2 respective carriers. These findings predict a provable further spread of ESBL producers in both community and clinical settings.
  • Ai Fujita, Kouji Kimura, Satoru Yokoyama, Wanchun Jin, Jun-ichi Wachino, Keiko Yamada, Hiroyuki Suematsu, Yuka Yamagishi, Hiroshige Mikamo, Yoshichika Arakawa
    PLoS One 10(11) 2015年11月  
    We characterized 12 clinical isolates of Klebsiella oxytoca with the extended-spectrum beta-lactamase (ESBL) phenotype (high minimum inhibitory concentration [MIC] values of ceftriaxone) recovered over 9 months at a university hospital in Japan. To determine the clonality of the isolates, we used pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and PCR analyses to detect bla(RBI), which encodes the beta-lactamase RbiA, OXY-2-4 with overproduce-type promoter. Moreover, we performed the isoelectric focusing (IEF) of beta-lactamases, and the determination of the MICs of beta-lactams including piperacillin/tazobactam for 12 clinical isolates and E. coli HB101 with pKOB23, which contains blaRBI, by the agar dilution method. Finally, we performed the initial screening and phenotypic confirmatory tests for ESBLs. Each of the 12 clinical isolates had an identical PFGE pulsotype and MLST sequence type (ST9). All 12 clinical isolates harbored identical blaRBI. The IEF revealed that the clinical isolate produced only one beta-lactamase. E. coli HB101 (pKOB23) and all 12 isolates demonstrated equally resistance to piperacillin/tazobactam (MICs, > 128 mu g/ml). The phenotypic confirmatory test after the initial screening test for ESBLs can discriminate beta-lactamase RbiA-producing K. oxytoca from beta-lactamase CTX-M-producing K. oxytoca. Twelve clinical isolates of K. oxytoca, which were recovered from an outbreak at one university hospital, had identical genotypes and produced beta-lactamase RbiA that conferred resistance to piperacillin/tazobactam. In order to detect K. oxytoca isolates that produce RbiA to promote research concerning beta-lactamase RbiA-producing K. oxytoca, the phenotypic confirmatory test after the initial screening test for ESBLs would be useful.
  • Kamiya C, Kimura K, Doyama Y, Miyazaki A, Morimoto M, Banno H, Nagano N, Jin W, Wachino J, Yamada K, Arakawa Y
    Diagnostic Microbiology and Infectious Disease 82(4) 269-273-273 2015年  
  • Goto K, Kawamura K, Arakawa Y
    Japanese Journal of Infectious Diseases 68(3) 196-202-202 2015年  
    We evaluated the effects of qnrA on survival of bacteria exposed to a lethal ciprofloxacin (CIP) concentration and development of quinolone resistance through the accumulation of amino acid substitutions in quinolone resistance-determining regions (QRDRs) of GyrA and ParC, targets of quinolones, in Escherichia coli. CIP-susceptible E. coli strains of different O-serotypes (O1, O6, O18, O25b, O74, and O78) were transformed by a recombinant plasmid harboring qnrA, and the parent strains and their transformants were subjected to killing curve assays and adaptation tests. In the killing curve assay at 2 × the minimum inhibitory concentration of CIP, the viable bacterial cell numbers of strains O1, O6, and O25b were maintained at 105–108 CFU/mL after 24-h incubation, while the remaining strains showed a 105-fold reduction in viable cell numbers. In the adaptation test, a Ser83-Leu substitution in the QRDR of GyrA was identified earlier in the parent strains of O25b and O1 than in their transformants, suggesting that the acquisition of qnrA did not necessarily accelerate the rate of accumulation of amino acid substitutions in the QRDR. We confirmed that the presence of qnrA contributed to increased survival of the E. coli strains displaying certain O-serotypes. Further studies are necessary to evaluate the precise effects of qnrA on quinolone resistance acquisition by Enterobacteriaceae.
  • Mura T, Kawamura K, Wachino J, Shibayama K, Arakawa Y
    Diagnostic Microbiology and Infectious Disease 83(1) 25-29 2015年  
  • Umene YD, Wong LK, Satoh T, Yamane K, Matsui M, Riley LW, Arakawa Y, Suzuki S
    Journal of Clinical Microbiology 53(2) 681-686 2015年  
  • Seki T, Kimura K, Reid M.E, Miyazaki A, Banno H, Jin W, Wachino J, Yamada K, Arakawa Y
    Journal of Antimicrobial Chemotherapy 70(10) 2725-2728-2728 2015年  
  • Yamada R, Kimura K, Nagano N, Nagano Y, Suzuki S, Jin W, Wachino J, Yamada K, Shibayama K, Arakawa Y
    Japanese Journal of Infectious Diseases 68(4) 326-329-329 2015年  
    Since Group B Streptococcus (GBS, Streptococcus agalactiae) clinical isolates are believed to be uniformly susceptible to β-lactams, penicillin G has been used as the first-line agent for the prevention and treatment of GBS infections. However, the existence and characteristics of GBS isolates with reduced penicillin susceptibility (PRGBS) have recently been reported in Japan. Moreover, the sequence type (ST) 458 is predominant among the PRGBS in Japan. Although the majority of the PRGBS isolates in Japan have been recovered from respiratory specimens of adults, no information on the genotype of these isolates is available. Therefore, whether ST458 predominates among GBS isolates obtained from such specimens is not known. In this study, we characterized the STs of 38 penicillin-susceptible GBS isolates (PSGBS) recovered from respiratory specimens and compared them to the reported PRGBS STs. ST458, the predominant ST among the PRGBS isolates studied (10/19, 53%), was not found in the PSGBS isolates. Thirty-six PSGBS isolates belonged to the ST1/19/10 group (includes 6 different STs), and the remaining 2 isolates belonged to that of ST23. Further, the PRGBS isolates were divided into the ST1 (3 STs), and ST23 (2 STs) groups. ST458 was not predominant among the PSGBS isolates recovered from respiratory specimens in Japan and may therefore be specific to the PRGBS. Thus, the ST distribution of the PRGBS isolates does not reflect that of the PSGBS.
  • Yamaguchi Y, Matsueda S, Matsunaga K, Takashio N, Toma-Fukai S, Yamagata Y, Shibata N, Wachino J, Shibayama K, Arakawa Y, Kurosaki H
    Biol Pharm Bull 38(1) 96-101 2015年  
  • Kimura K, Nagano N, Arakawa Y
    Journal of Antimicrobial Chemotherapy/ Oxford University Press 70(6) 1601-1603 2015年  
  • Ito R, Shindo Y, Kobayashi D, Ando M, Jin W, Wachino J, Yamada K, Kimura K, Yagi T, Hasegawa Y, Arakawa Y
    Journal Clinical Microbiology/ASM Press 53(3) 879-886 2015年  
  • Jin W, Wachino J, Kimura K, Yamada K, Arakawa Y
    Journal of Antimicrobial Chemotherapy. 70(5) 1331-1337 2015年  
  • Shigetarou Mori, Hyun Kim, Emiko Rimbara, Yoshichika Arakawa, Keigo Shibayama
    Bioscience, biotechnology, and biochemistry 79(2) 236-8 2015年  
    Diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap4A) phosphorylase from Mycobacterium tuberculosis H37Rv (MtAPA) belongs to the histidine triad motif (HIT) superfamily, but is the only member with an alanine residue at position 149 (Ala-149). Enzymatic analysis revealed that the Ala-149 deletion mutant displayed substrate specificity for diadenosine 5',5'''-P(1),P(5)-pentaphosphate and was inactive on Ap4A and other substrates that are utilized by the wild-type enzyme.
  • Suzuki T, Kimura K, Suzuki H, Banno H, Jin W, Wachino J, Yamada K, Arakawa Y
    The Journal of Antimicrobial Chemotherapy/ Oxford University Press 70(4) 1258-1259 2015年  
  • Nagasaka Y, Kimura K, Yamada K, Wachino J, Jin W, Notake S, Yanagisawa H, Arakawa Y
    Microbial Drug Resistance 21(2) 224-233 2015年  
  • Jun-ichi Wachino, Kouji Kimura, Keiko Yamada, Wanchun Jin, Yoshichika Arakawa
    JOURNAL OF CLINICAL MICROBIOLOGY 52(10) 3827-3828 2014年10月  
  • S. Mori, H. Kim, E. Rimbara, Y. Arakawa, K. Shibayama
    FEBS JOURNAL 281 584-585 2014年9月  
  • Hiromitsu Kitanaka, Masa-aki Sasano, Satoru Yokoyama, Masahiro Suzuki, Wanchun Jin, Masami Inayoshi, Mitsuhiro Hori, Jun-ichi Wachino, Kouji Kimura, Keiko Yamada, Yoshichika Arakawa
    Emerg Infect Dis. 20(9) 1574-1576 2014年9月  
  • Mitsuaki Nagasawa, Mitsuo Kaku, Kazunari Kamachi, Keigo Shibayama, Yoshichika Arakawa, Keizo Yamaguchi, Yoshikazu Ishii
    JOURNAL OF INFECTION AND CHEMOTHERAPY 20(9-10) 635-638 2014年9月  
    Using the loop-mediated isothermal amplification (LAMP) method, we developed a rapid assay for detection of 16S rRNA methylase genes (rmtA, rmtB, and armA), and investigated 16S rRNA methylase-producing strains among clinical isolates. Primer Explorer V3 software was used to design the LAMP primers. LAMP primers were prepared for each gene, including two outer primers (F3 and B3), two inner primers (FIP and BIP), and two loop primers (LF and LB). Detection was performed with the Loopamp DNA amplification kit. For all three genes (rmtA, rmtB, and armA), 10(2) copies/tube could be detected with a reaction time of 60 mm. When nine bacterial species (65 strains saved in National Institute of Infectious Diseases) were tested, which had been confirmed to possess rmtA, rmtB, or armA by PCR and DNA sequencing, the genes were detected correctly in these bacteria with no false negative or false positive results. Among 8447 clinical isolates isolated at 36 medical institutions, the LAMP method was conducted for 191 strains that were resistant to aminoglycosides based on the results of antimicrobial susceptibility tests. Eight strains were found to produce 16S rRNA methylase (0.09%), with rmtB being identified in three strains (0.06%) of 4929 isolates of Enterobacteriaceae, rmtA in three strains (0.10%) of 3284 isolates of Pseudomonas aeruginosa, and armA in two strains (0.85%) of 234 isolates of Acinetobacter spp. At present, the incidence of strains possessing 16S rRNA methylase genes is very low in Japan. However, when Gram-negative bacteria showing high resistance to aminoglycosides are isolated by clinical laboratories, it seems very important to investigate the status of 16S rRNA methylase gene-harboring bacilli and monitor their trends among Japanese clinical settings. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
  • Genki Nakamura, Jun-ichi Wachino, Natsumi Sato, Kouji Kimura, Keiko Yamada, Wanchun Jin, Keigo Shibayama, Tetsuya Yagi, Kumiko Kawamura, Yoshichika Arakawa
    JOURNAL OF CLINICAL MICROBIOLOGY 52(9) 3175-3179 2014年9月  
    The number of reports concerning Escherichia coli clinical isolates that produce glutathione S-transferases responsible for fosfomycin resistance (FR-GSTs) has been increasing. We have developed a disk-based potentiation test in which FR-GST producers expand the growth inhibition zone around a Kirby-Bauer disk containing fosfomycin in combination with sodium phosphonoformate (PPF). PPF, an analog of fosfomycin, is a transition-state inhibitor of FosA(PA), a type of FR-GST from Pseudomonas aeruginosa. Considering its mechanism of action, PPF was expected to inhibit a variety of FR-GSTs. In the presence of PPF, zone enlargement around the disk containing fosfomycin was observed for FosA3-, FosA4-, and FosC2-producing E. coli clinical isolates. Moreover, the growth inhibition zone was remarkably enlarged when the Mueller-Hinton (MH) agar plate contained 25 mu g/ml glucose-6-phosphate (G6P). When we retrospectively tested 12 fosfomycin-resistant (MIC, >= 256 mu g/ml) E. coli clinical isolates from our hospital with the potentiation test, 6 FR-GST producers were positive phenotypically by potentiation disk and were positive for FR-GST genes: 5 harbored fosA3 and 1 harbored fosA4. To identify the production of FR-GSTs, we set the provisional cutoff value, 5-mm enlargement, by adding PPF to a fosfomycin disk on the MH agar plates containing G6P. Our disk-based potentiation test reliably identifies FR-GST producers and can be performed easily; therefore, it will be advantageous in epidemiological surveys and infection control of fosfomycin-resistant bacteria in clinical settings.
  • Noriyuki Nagano, Yukiko Nagano, Masami Toyama, Kouji Kimura, Keigo Shibayama, Yoshichika Arakawa
    JOURNAL OF CLINICAL MICROBIOLOGY 52(9) 3406-3410 2014年9月  
    We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTBr PSGBS). The CTBr PSGBS isolates, for which augmented MICs of cefaclor and ceftizoxime were found, shared a T394A substitution in penicillin-binding protein 2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A substitution in the transglycosidase domain of PBP 1A would have no effect on the level of resistance to ceftibuten.
  • Masahiro Suzuki, Eriko Hosoba, Mari Matsui, Yoshichika Arakawa
    JOURNAL OF CLINICAL MICROBIOLOGY 52(8) 2925-2932 2014年8月  
    Antimicrobial resistance issues have become a global health concern. The rapid identification of multidrug-resistant microbes, which depends on microbial genomic information, is essential for overcoming growing antimicrobial resistance challenges. However, genotyping methods, such as multilocus sequence typing (MLST), for identifying international epidemic clones of Acinetobacter baumannii are not easily performed as routine tests in ordinary clinical laboratories. In this study, we aimed to develop a novel genotyping method that can be performed in ordinary microbiology laboratories. Several open reading frames (ORFs) specific to certain bacterial genetic lineages or species, together with their unique distribution patterns on the chromosomes showing a good correlation with the results of MLST, were selected in A. baumannii and other Acinetobacter spp. by comparing their genomic data. The distribution patterns of the ORFs were visualized by agarose gel electrophoresis after multiplex PCR amplification and digitized. A. baumannii sequence types (STs) corresponding to international clones I and II were successfully discriminated from other STs and Acinetobacter species by detecting the distribution patterns of their ORFs using the multiplex PCR developed here. Since bacterial STs can be easily expressed as digitized numeric data with plus (-) expressed as 1 and minus (+) expressed as 0, the results of the method can be easily compared with those obtained by different tests or laboratories. This PCR-based ORF typing (POT) method can easily and rapidly identify international epidemic clones of A. baumannii and differentiate this microbe from other Acinetobacter spp. Since this POT method is easy enough to be performed even in ordinary clinical laboratories, it would also contribute to daily infection control measures and surveillance.
  • Hiromitsu Kitanaka, Jun-ichi Wachino, Wanchun Jin, Satoru Yokoyama, Masa-aki Sasano, Mitsuhiro Hori, Keiko Yamada, Kouji Kimura, Yoshichika Arakawa
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 58(8) 4978-4979 2014年8月  
  • Banno H, Kimura K, Tanaka Y, Kitanaka H, Jin W, Wachino J, Yamada K, Shibayama K, Arakawa Y
    J Clin Microbiol 52(6) 2169-2171 2014年6月  
  • Mari Matsui, Satowa Suzuki, Kunikazu Yamane, Masato Suzuki, Toshifumi Konda, Yoshichika Arakawa, Keigo Shibayama
    JOURNAL OF MEDICAL MICROBIOLOGY 63(63) 870-877 2014年6月  
    We performed a comparative molecular analysis on three types of clinically isolated Acinetobacter spp.: epidemic sequence types (STs) of Acinetobacter baumannii (epidemic ST-AB), non-epidemic sequence types of A. baumannii (non-epidemic ST-AB) and non-baumannii Acinetobacter spp. A total of 87 isolates - 46 A. baumannii, 25 A. pittii and 16 A. nosocomialis - from 43 hospitals were analysed. Of these, 31 A. baumannii isolates were ST1 or ST2 according to the Pasteur Institute multilocus sequence typing scheme and were defined as epidemic ST-AB. The other 15 A. baumannii isolates were defined as non-epidemic ST-AB. The epidemic ST-AB isolates harboured the bla(OXA-23-like) gene or had an ISAba1 element upstream of bla(OXA-51-like), or both, whereas non-epidemic ST-AB and non-baumannii Acinetobacter spp. isolates harboured bla(OXA-58-like) or metallo-beta-lactamase genes, or both. The proportion of multidrug-resistant isolates was significantly higher in the epidemic ST-AB isolates (48%) than that in the other types of Acinetobacter isolates (5%) (P<0.05). In addition, epidemic ST-AB isolates exhibited a relatively higher proportion of fluoroquinolone resistance. We demonstrated that, in terms of genotypes and phenotypes of antimicrobial resistance, non-epidemic ST-AB isolates shared more similarity with non-baumannii Acinetobacter spp. isolates than with epidemic ST-AB isolates, regardless of bacterial species. In addition, this study revealed that, even in Japan, where IMP-type metallo-beta-lactamase producers are endemic, epidemic ST-AB harbouring bla(IMP) have not yet emerged.
  • Marieke J. Bart, Simon R. Harris, Abdolreza Advani, Yoshichika Arakawa, Daniela Bottero, Valerie Bouchez, Pamela K. Cassiday, Chuen-Sheue Chiang, Tine Dalby, Norman K. Fry, Maria Emilia Gaillard, Marjolein van Gent, Nicole Guiso, Hans O. Hallander, Eric T. Harvill, Qiushui He, Han G. J. van der Heide, Kees Heuvelman, Daniela F. Hozbor, Kazunari Kamachi, Gennady I. Karataev, Ruiting Lan, Anna Lutynska, Ram P. Maharjan, Jussi Mertsola, Tatsuo Miyamura, Sophie Octavia, Andrew Preston, Michael A. Quail, Vitali Sintchenko, Paola Stefanelli, M. Lucia Tondella, Raymond S. W. Tsang, Yinghua Xu, Shu-Man Yao, Shumin Zhang, Julian Parkhill, Frits R. Mooi
    MBIO 5(2) 1074-14 2014年3月  
    Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.
  • Kumiko Kawamura, Kensuke Goto, Kunihiko Nakane, Yoshichika Arakawa
    FOODBORNE PATHOGENS AND DISEASE 11(2) 104-110 2014年2月  
    Contamination of retail meat with extended-spectrum -lactamase (ESBL)-producing Escherichia coli has been reported, but only limited data have been documented in Japan. One hundred fifty-three retail foods including chicken meat, beef, pork, and vegetables were purchased from 29 supermarkets between January and October in 2010. ESBL producers were recovered from each food sample using McConkey agar plate supplemented with 1mg/L of cefotaxime. ESBL type was identified by DNA sequencing analysis after polymerase chain reaction amplification. Antibiogram, O serotype, plasmid replicon type, pulsotype, and multilocus sequence type were also determined. Fifty-two epidemiologically unrelated Escherichia coli isolates producing ESBL were recovered from 35 (22.9%) of 153 samples, all of which were chicken meat. ESBL types were mainly CTX-M-2 group followed by CTX-M-1 group and CTX-M-8 group. The numbers of bacterial isolates (8 of 21, 38.1%) harboring bla(CTX-M-8) recovered from imported meat samples were significantly larger than those of domestic ones (one of 31, 3.2%) (p<0.05). Nine O serotypes (mainly O8, O25, and O1) were found, together with O-antigen untypable (OUT). Four E. coli belonging to the O25b:H4-ST131 clone were recovered from domestic (n=1) and imported meat samples (n=3), respectively. These four isolates were susceptible to fluoroquinolones, although the E. coli O25b:H4-ST131 clone producing CTX-M-15, which is predominant in human isolates, is usually resistant to fluoroquinolones. By contrast, five CTX-M-15-producing E. coli strains were recovered only from domestic meat samples, and their serotypes were O8 or OUT instead of predominant serotype O25b. Our results showed that ESBL-producing E. coli isolates recovered from retail chicken meat samples in Japan are generally divergent in both genetic and serological aspects. Further comparative analyses of bla(CTX-M)-mediating genetic elements would be continued in the next step to characterize the ESBL producers from retail foods in Japan.
  • Hattori T, Kawamura K, Arakawa Y
    Japanese Journal of Infectious Diseases 66(6) 512-518-518 2013年  
    The recent increase in gram-negative bacteria coproducing multiple classes of β-lactamases has made it difficult to accurately identify metallo-β-lactamase (MBL) producers. In the present study, six methods for detecting MBL producers were compared using 56 gram-negative bacterial isolates that produce various β-lactamases. Sodium mercaptoacetic acid (SMA) and EDTA were used as inhibitors for a double-disk synergy test (DDST), and antimicrobial agents, including ceftazidime (CAZ), imipenem, and meropenem (MEPM), along with the distance between the disks, were compared. The Etest®, dry-plate DPD1®, Cica-Beta®, and modified Hodge test were also compared. Among the six methods compared, DDST using the SMA disk showed the highest sensitivity (Se) and specificity (Sp). In DDST, the clearest appearance of growth inhibition was observed when the distance between the disks was maintained at approximately 5 mm. A combination of CAZ and SMA successfully detected only MBL-producing isolates (Se, 87.5%; Sp, 100%), and MEPM exhibited the best performance in combination with SMA in the detection of MBL producers coproducing other classes of β-lactamases such as CTX-M- and CMY-type enzymes (Se, 79.1%; Sp, 100%). DDST using SMA and CAZ and/or MEPM is a simple, specific, and cost-effective method to screen MBL producers in routine clinical laboratory testing.
  • Sato N, Kawamura K, Nakane K, Wachino J, Arakawa Y
    Microbial Drug Resistance 19(6) 477-482 2013年  
  • Matsui M, Suzuki S, Suzuki M, Arakawa Y, Shibayama K
    Journal of Microbiological Methods 94(2) 121-124 2013年  
  • Kimura K, Yanagisawa H, Wachino J, Shibayama K, Arakawa Y
    Japanese Journal of Infectious Diseases 66(6) 546-548-548 2013年  
    Streptococcus agalactiae (group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis and an important pathogen in elderly patients and those with underlying diseases. The diagnosis of GBS infections is primarily based on culture of GBS. Some clinical laboratories perform the Christie-Atkins-Munch-Peterson (CAMP) test for discrimination of GBS from other streptococci. Here, we developed a rapid GBS identification method, i.e., the loop-mediated isothermal amplification (LAMP) method for detecting the cfb gene encoding the CAMP factor. This method detected at least 4 copies of the cfb gene in GBS under isothermal conditions with in a short time (65℃, within 90 min). No inappropriate amplification of nucleotide by this method was observed when the chromosomal DNA of 17 streptococci and enterococci species, other than GBS, were used as templates. In this investigation, we successfully developed a LAMP method for rapid and highly sensitive detection of GBS, which provides a beneficial alternative to the conventional CAMP test.
  • Wachino J, Yamaguchi Y, Mori S, Kurosaki H, Arakawa Y, Shibayama K
    Antimicrob Agents Chemother 57(1) 101-109 2013年  
  • Matsuoka M, Sasaki T, Seki N, Kobayashi M, Sawabe K, Sasaki Y, Shibayama K, Sasaki T, Arakawa Y
    Clin Vaccine Immunol 20(4) 620-626 2013年  
  • Nagano N, Endoh Y, Nagano Y, Toyama M, Matsui M, Shibayama K, Arakawa Y
    Jpn J Infect Dis 66(1) 79-81-81 2013年  
  • Kimura K, Wachino J, Kurokawa H, Matsui M, Suzuki S, Yamane K, Nagano N, Shibayama K, Arakawa Y
    J Antimicrob Chemother 68(7) 1533-1536 2013年  

MISC

 1124
  • 有馬 颯人, 山口 佳宏, 牛嶋 一豪, 松本 祥吾, 和知野 純一, 荒川 宜親, 黒崎 博雅
    日本生化学会大会プログラム・講演要旨集 96回 [1P-182] 2023年10月  
  • 和知野 純一, 法月 千尋, 荒川 宜親
    日本医学検査学会抄録集 72回 32-32 2023年5月  
  • 畑中 公基, 山田 景子, 武田 明, 木戸 裕勝, 佐川 美恵, 吉川 誠一, 小野 伸高, 荒川 宜親
    医学検査 71(4) 748-753 2022年10月  
    症例は60代女性。右下腿開放性骨折受傷後に脛骨慢性骨髄炎を発症した。各種抗菌薬の投与,病巣掻爬,抗菌薬含有人工骨やセメントビーズ留置が5回施行された。受傷4年6ヵ月後,慢性骨髄炎の根治目的に今回の入院となった。病巣掻爬術が施行され,嫌気性菌,ブドウ糖非発酵グラム陰性桿菌を検出。複数の抗菌薬投与の後,第45病日以降の骨周囲培養から,Staphylococcus capitis subspecies urealyticusが分離された。寒天平板希釈法および微量液体希釈法での薬剤感受性試験の結果,vancomycin(VCM),teicoplanin(TEIC),daptomycin(DAP)で高いMIC結果を得た(それぞれ4,64,2μg/mL)。DAP投与歴は無いがDAP非感性を示した。第76病日よりlinezolidの投与を開始後,解熱,白血球数低下と創部の肉眼的所見の改善が見られ,第79病日に骨周囲培養の陰性化を確認,第133病日に退院となった。本症例は受傷2年2ヵ月後にVCM含有人工骨留置を行っており,その際,高濃度のVCMに曝露されたことで細胞壁が肥厚し感受性が低下した株が選択された可能性が考えられる。本症例のように過去にVCMやTEICの局所投与歴があり,同薬に感受性が低下した菌が分離された際は,DAP投与歴が無くとも薬剤感受性試験を実施し,微生物学的有効性を推定して投薬を判断することが重要であると考えられた。(著者抄録)
  • 池田 翼, 鈴木 理史, 荒川 宜親, 木村 幸司, 金 万春, 和知野 純一
    感染症学雑誌 96(臨増) 134-134 2022年3月  
  • 荒川 宜親
    修文大学紀要 (13) 45-48 2022年3月  
    カルバペネム系抗菌薬に耐性を獲得した各種のグラム陰性菌が世界各地の医療現場で増加し,それらの多くは,カルバペネム系以外の広範囲の抗菌薬にも多剤耐性を示し,ガン患者や高度医療を受ける患者の生命予後を脅かす大きな問題になっている.そこで,多剤耐性菌感染症の治療に有用な新規化合物の開発を,AMED(日本医療研究開発機構)の支援を受けて推進している.(著者抄録)
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書籍等出版物

 26
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講演・口頭発表等

 107
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担当経験のある科目(授業)

 1
  • 1989年 - 現在
    医学細菌学、病原細菌学、薬剤耐性菌等  (名古屋大学 [医、保健、工]、群馬大学 [医]、千葉大学 [薬]、東京薬科大学 [薬]、愛知学院大学 [歯・薬]、岐阜薬科大学 [薬]、愛知医科大学[医]、 他)

所属学協会

 6
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共同研究・競争的資金等の研究課題

 32
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産業財産権

 25
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メディア報道

 1
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