研究者詳細 - 髙橋　聡

論文 - 髙橋　聡

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Evaluation of new algorithm using TPLA as an initial syphilis screening test.

Ryosei Murai, Koji Yamada, Hitoshi Yonezawa, Nozomi Yanagihara, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 1 ) 68 - 70 2019年01月 [国際誌]

We retrospectively compared the performance of an existing syphilis diagnostic algorithm with a new algorithm that analyzes the results of Treponema pallidum latex agglutination (TPLA) tests. Of the 100 clinical blood samples, 51 were classified as positive through both Mediace TPLA and ESPLINE TP; 2/51 were classified as negative by Architect Syphilis TP, whereas 1/51 was negative as per LUMIPULSE Presto TP. The false positive rate when the results of Mediace TPLA and ESPLINE TP were combined was 1.96% versus 0% for both Architect Syphilis TP and LUMIPULSE Presto TP. The sensitivity of Mediace TPLA (98%) was comparable to that of Architect Syphilis TP (98%) but lower than that of LUMIPULSE Presto TP (100%). The specificity of Mediace TPLA was 98.0% versus 100% for Architect Syphilis TP, and versus 100% for LUMIPULSE Presto TP. We conclude that the performance of Mediace TPLA in combination with a reverse algorithm is nearly equal to that of enzyme immunoassay (EIA) or chemiluminescence immunoassay (CIA). Because TPLA is low cost, highly sensitive method for IgM detection, and is easy to operate, we have recommended its adoption for initial syphilis screening tests.

Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in mcr-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-H30Rx and Non-x.

Toyotaka Sato, Tsukasa Shiraishi, Yoshiki Hiyama, Hiroyuki Honda, Masaaki Shinagawa, Masaru Usui, Koji Kuronuma, Naoya Masumori, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy 62 ( 9 ) 2018年09月 [国際誌]

Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (mcr) gene-negative colistin-resistant Escherichia coli clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-H30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter). In this study, we investigated the colistin resistance mechanism and identified novel amino acid substitutions or deletions in the PmrAB two-component system that activates eptA (encoding a phosphoethanolamine transferase) and arnT (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates. SRE34 possessed deletion Δ27-45 (LISVFWLWHESTEQIQLFE) in PmrB, SRE44 possessed substitution L105P in PmrA, and both SME222 and SME296 included substitution G206D in PmrB. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that lipid A is modified with phosphoethanolamine in all four isolates. Deletion of pmrAB decreased colistin MICs to 0.5 mg/liter and lowered eptA and arnT expression. Chromosomal replacement of mutated pmrA or pmrB in colistin-susceptible O25b:H4-ST131 strain SME98 (colistin MIC = 0.5 mg/liter) increased the colistin MIC to that of the respective parent colistin-resistant isolate. In addition, SME98 mutants in which pmrAB was replaced with mutated pmrAB showed no significant differences in bacterial growth and competition culture from the parent strain, except for the mutant with L105P in PmrA, whose growth was significantly suppressed in the presence of the parent strain. In conclusion, some O25b:H4-ST131 strains appear to acquire colistin resistance via phosphoethanolamine modification of lipid A through amino acid changes in PmrAB, and the amino acid changes in PmrB do not influence bacterial growth.

Multiclonal Expansion and High Prevalence of β-Lactamase-Negative Haemophilus influenzae with High-Level Ampicillin Resistance in Japan and Susceptibility to Quinolones.

Hiroyuki Honda, Toyotaka Sato, Masaaki Shinagawa, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Tsukasa Shiraishi, Koji Kuronuma, Satoshi Takahashi, Hiroki Takahashi, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy 62 ( 9 ) 2018年09月 [国際誌]

β-Lactam-resistant Haemophilus influenzae is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) isolates in Japan has been reported. However, the reasons for the expansion are unknown. High-BLNAR strains possess an amino acid substitution, either Asn526Lys (group III) or Arg517His (group III-like) in addition to Ser385Thr, in penicillin-binding protein 3 (PBP3). To determine the current prevalence of high-BLNAR strains and the mechanisms behind their expansion in Japan, their prevalence, PBP3 types, multilocus sequence types, and susceptibilities to quinolones approved in Japan as alternatives were determined. Sixty percent of H. influenzae clinical isolates (62/104 isolates) were β-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) strains. Among BLNAR isolates, 92% (57/62 isolates) were high-BLNAR strains. Most isolates were classified as belonging to group III, which contained many genotypes (11 PBP3 types and 25 sequence types). These results indicated that the expansion of high-BLNAR isolates was multiclonal and such strains are still predominant in Japanese clinical settings. One high-BLNAR isolate harbored the novel amino acid substitution Asn526Met in addition to Ser385Thr in PBP3, suggesting a new group (group IV). No quinolone-resistant H. influenzae isolates were identified. The MICs for the quinolones (moxifloxacin, garenoxacin, and tosufloxacin) were similar to that for levofloxacin, whereas sitafloxacin exhibited a lower MIC. However, we obtained 4 H. influenzae isolates with decreased quinolone susceptibility with the amino acid substitution Ser84Leu in GyrA, and 3 of those isolates were high-BLNAR isolates. In summary, this study shows that multiclonal high-BLNAR strains predominate in a Japanese university hospital. Isolates remain sensitive to quinolones, but vigilance is required to prevent the development of fluoroquinolone resistance in high-BLNAR strains.

Management of fungus balls as a result of Candida albicans.

Yoshiki Hiyama, Satoshi Takahashi, Naoya Masumori

International journal of urology : official journal of the Japanese Urological Association 25 ( 6 ) 635 - 636 2018年06月 [国際誌]

Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin.

Shin-Ichi Yokota, Hiroshi Hakamada, Soh Yamamoto, Toyotaka Sato, Tsukasa Shiraishi, Masaaki Shinagawa, Satoshi Takahashi

International journal of antimicrobial agents 51 ( 6 ) 888 - 896 2018年06月 [国際誌]

Pseudomonas aeruginosa is an important etiological agent of opportunistic infections. Injectable colistin is available as a last-line treatment option for multidrug-resistant P. aeruginosa infections. When cells were inoculated at a high number, colistin-susceptible P. aeruginosa grew on agar medium containing colistin at a concentration 10-fold higher than the minimum inhibitory concentration without acquiring colistin resistance. This study examined the responsible mechanism for growth in the presence of a high concentration of colistin. Cell wash fluid derived from P. aeruginosa efficiently reduced colistin antimicrobial activity. This reduction was mediated by lipopolysaccharide (LPS) in the wash fluid. Extracellular LPS inhibited colistin activity more effectively than cell-bound LPS in fixed cells. Cell wash fluids from Escherichia coli and Acinetobacter baumannii also reduced colistin activity; however, they were less potent than those from P. aeruginosa. The amount of LPS in cell wash fluid from P. aeruginosa was approximately 10-fold higher than that in fluid from E. coli or A. baumannii. In conclusion, cell-free LPS derived from bacterial cells inhibited the antimicrobial activity of colistin, and this effect was greatest for P. aeruginosa. Thus, large amounts of broken and dead cells of P. aeruginosa at infection foci will reduce the effectiveness of colistin, even against cells that have not yet acquired resistance.

Isolation of a mcr-1-harbouring Escherichia coli isolate from a human clinical setting in Sapporo, Japan.

Toyotaka Sato, Akira Fukuda, Masaru Usui, Masaaki Shinagawa, Tsukasa Shiraishi, Yutaka Tamura, Satoshi Takahashi, Shin-Ichi Yokota

Journal of global antimicrobial resistance 13 20 - 21 2018年06月 [国際誌]

Oral administration of cernitin pollen extract (Cernilton® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

Yoshikazu Togo, Daishi Ichioka, Jun Miyazaki, Yoshiko Maeda, Koji Kameyama, Mitsuru Yasuda, Yoshiki Hiyama, Satoshi Takahashi, Hiroshi Nagae, Seiichi Hirota, Shingo Yamamoto

International journal of urology : official journal of the Japanese Urological Association 25 ( 5 ) 479 - 485 2018年05月 [国際誌]

OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

A Case of Acquired Hemophilia A: Usefulness of Various Methods for Judging Mixing Test Results for Monitoring the Effect of Immunosuppressive Therapy.

Ryosuke Moriai, Nozomi Yanagihara, Akemi Endoh, Satoru Yamada, Maki Mochizuki, Takashi Kondo, Teruo Endoh, Koichi Asanuma, Satoshi Takahashi

Clinical laboratory 64 ( 4 ) 623 - 626 2018年04月 [国際誌]

BACKGROUND: Measurement of FVIII inhibitor (FVIII INH) levels is important for determining the effect of immunosuppressive therapy on acquired hemophilia A (AHA). However, FVIII INH can only be measured at a limited number of laboratories, which means that there are delays in obtaining the results at many sites. METHODS: A series of mixing tests were carried out in a case of AHA, followed by comparison of various methods for judging the obtained results in association with a change of FVIII INH. The mixing test results were judged using the visual waveform pattern method and the index of circulating anticoagulant (ICA), as well as the difference between the APTT values of delayed-type and immediate-type waveforms (APTT D-I) as a numerical index. RESULTS: All examined judgment methods reflected the change in FVIII INH, but ICA and APTT D-I were particularly sensitive for capturing this. CONCLUSIONS: Our results suggest that a series of mixing tests are useful for rapid monitoring of the effect of immunosuppressive therapy on AHA.

Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other beta-lactams.

Masachika Saeki, Masaaki Shinagawa, Yuki Yakuwa, Shinya Nirasawa, Yuki Sato, Nozomi Yanagihara, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 3 ) 212 - 215 2018年03月 [国際誌]

The existence of a cefazolin inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA), which is speculated to be a reason for cefazolin treatment failure in MSSA infections, is controversial. In Japan, although cefazolin is one of the therapeutic choices for patients with MSSA infection, there are few reports of this effect. Additionally, the association between InE and blaZ type in beta-lactams other than cefazolin has not been well documented. In this study, we confirmed an MSSA InE in several beta-lactams, including cefazolin, and its relationship with blaZ, using 52 MSSA isolates from blood cultures. Three isolates (5.8%) that possessed type A blaZ showed a pronounced cefazolin InE. Five isolates (9.6%) showed pronounced InE with sulbactam/ampicillin; four isolates had type C blaZ and one had type A blaZ. However, we confirmed InE in MSSA isolates with blaZ not only type A and C but also B and D. For cefotaxime, ceftriaxone, imipenem, and meropenem, regardless of the presence of blaZ, we did not observe a significant increase in MICs at a high inoculum of MSSA. Hence, our results suggest that the above four beta-lactams are good alternatives to cefazolin if InE leads to treatment failure in a patient.

Quantification of Wilms' tumor 1 mRNA by digital polymerase chain reaction.

Yuki Koizumi, Daisuke Furuya, Teruo Endo, Kouichi Asanuma, Nozomi Yanagihara, Satoshi Takahashi

International journal of hematology 107 ( 2 ) 230 - 234 2018年02月 [国内誌]

Wilms' tumor 1 (WT1) is overexpressed in various hematopoietic tumors and widely used as a marker of minimal residual disease. WT1 mRNA has been analyzed using quantitative real-time polymerase chain reaction (real-time PCR). In the present study, we analyzed 40 peripheral blood and bone marrow samples obtained from cases of acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome at Sapporo Medical University Hospital from April 2012 to January 2015. We performed quantification of WT1 was performed using QuantStudio 3D Digital PCR System (Thermo Fisher Scientific‎) and compared the results between digital PCR and real-time PCR technology. The correlation between digital PCR and real-time PCR was very strong (R = 0.99), and the detection limits of the two methods were equivalent. Digital PCR was able to accurately detect lower WT levels compared with real-time PCR. Digital PCR technology can thus be utilized to predict WT1/ABL1 expression level accurately and should thus be useful for diagnosis or the evaluation of drug efficiency in patients with leukemia.

Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance in Enterococcus faecium from Japanese Clinical Setting.

Noriko Urushibara, Keisuke Suzaki, Mitsuyo Kawaguchiya, Meiji Soe Aung, Masaaki Shinagawa, Satoshi Takahashi, Nobumichi Kobayashi

Microbial drug resistance (Larchmont, N.Y.) 24 ( 1 ) 1 - 7 2018年 [国際誌]

High-level fluoroquinolone resistance is conferred by the mutation of conserved serine and acidic amino acids in the quinolone resistance-determining region (QRDR) of the A subunits of the type II topoisomerases, DNA gyrase (GyrA) and topoisomerase IV (ParC). In Japan, fluoroquinolone-resistant Enterococcus faecium continues to emerge in clinical settings. We analyzed 131 Japanese E. faecium clinical isolates for susceptibility to levofloxacin (LVFX), and QRDR mutational status. The bacterial collection had a high percentage of resistance (79%) and showed elevated drug minimal inhibitory concentrations (MICs). Eighty-three isolates had single or combined mutations in gyrA and/or parC; all were resistant to LVFX. A strong correlation was evident between log-transformed MICs and the total number of QRDR mutations (r = 0.7899), confirming the involvement of QRDR mutations in drug resistance, as previously described. Three-dimensional modeling indicated that the amino acid change(s) in QRDR could disrupt the interaction between the enzymes and drugs: the most common cause of quinolone resistance. Interestingly, eight isolates had a single mutation on gyrA and exhibited significantly reduced susceptibility. These data imply that either DNA gyrase or topoisomerase IV can be the primary target of fluoroquinolones, although topoisomerase IV is commonly thought to be the primary target in gram-positive bacteria.

同時期に泌尿器科病棟で経験した Helicobacter cinaedi による菌血症の4例

桧山佳樹, 髙橋聡, 西山直隆, 中江舞美, 藤居賢, 品川雅明, 舛森直哉

泌尿器科紀要 = Acta urologica Japonica ( 泌尿器科紀要刊行会 ) 63 ( 11 ) 461 - 463 2017年11月 [国内誌]

Here we report the outbreak of bacteremia caused by Helicobacter cinaedi (H. cinaedi) in the urology ward. Case 1 was a man in his seventies with prostate cancer. Bacteremia caused by H. cinaedi developed 6 days after robot-assisted radical prostatectomy. Case 2 was a man in his sixties with small cell carcinoma of the prostate. Bacteremia developed at 5 days of docetaxel therapy. Case 3 was a man in his fifties with left renal pelvis carcinoma. Bacteremia developed 3 days after laparoscopic left nephroureterectomy. Case 4 was a man in his seventies with right renal pelvic carcinoma and bladder cancer. Bacteremia developed 22 days after laparoscopic right nephroureterectomy and laparoscopic radical cystectomy. Each bacteremia occurred almost simultaneously. Fortunately, all 4 cases were treated by antibiotics successfully and there were no cases of recurrence. Whole environmental inspection of the ward did not reveal H. cinaedi. However, multilocus sequence typing proved the strains in cases 3 and 4 to be the same. Therefore, cross-infection was suspected. H. cinaedi can develop to a pathogen of immunocompromised infection. This report clarified that this pathogen can cause bacteremia in the urology ward.

DOI PubMed CiNii

The discrepancy between serum creatinine and cystatin C can predict renal function after treatment for postrenal acute kidney injury: multicenter study and pooled data analysis.

Masahiro Matsuki, Toshiaki Tanaka, Takeshi Maehana, Yuki Kyoda, Koji Ichihara, Kohei Hashimoto, Masahiro Yanase, Masanori Matsukawa, Hideki Adachi, Satoshi Takahashi, Naoya Masumori

Clinical and experimental nephrology 21 ( 5 ) 852 - 857 2017年10月 [国内誌]

BACKGROUND: Although serum cystatin C and creatinine are used as practical markers of renal function, the discrepancy between them in postrenal acute kidney injury (AKI) cases was reported. The aim of this study was to determine whether the preoperative serum cystatin C (pre-CysC) level could predict clinical outcomes after treatment in patients with postrenal AKI. METHODS: Patients who underwent urological interventions with postrenal AKI were enrolled in this prospective observational study. Associations among preoperative serum creatinine (pre-sCr), pre-CysC, and nadir postoperative serum creatinine (post-sCr) were evaluated. In addition, based on our results in combination with detailed data from the literature, a predictive equation for postoperative serum creatinine (post-sCr) was developed by simple regression analysis and validated using Bland-Altman plots. RESULTS: Finally, 19 patients were eligible for analysis in this study. The value calculated by subtracting pre-CysC (mg/L) from pre-sCr (mg/dl) had a strong correlation to the decrement of serum creatinine (r = 0.9508, p < 0.0001). We added the data of 16 patients obtained from the literature to our series, which were totally randomized into 2 groups, training set and validation set in a 2:1 ratio (n = 23 and 12, respectively) to develop and validate a predictive equation for post-sCr. The mean difference between the predictive and actual post-sCr, -0.68 mg/dl (95% CI -1.62 to 0.26) in the validation set was within the limits of agreement. CONCLUSION: We showed that the discrepancy between pre-sCr and pre-CysC could predict improvement of renal function after intervention in patients with postrenal AKI.

The efficacy of faropenem for patients with acute cystitis caused by extended spectrum β-lactamase producing Escherichia coli.

Keiko Fujino, Yoshiki Hiyama, Teruhisa Uehara, Koji Ichihara, Jiro Hashimoto, Satoshi Fujii, Masaaki Shinagawa, Satoshi Takahashi, Naoya Masumori

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 23 ( 5 ) 336 - 338 2017年05月 [国際誌]

The number of patients with acute cystitis caused by extended spectrum β lactamase (ESBL)-producing Escherichia coli (E. coli) is increasing gradually. Although it is reported that ESBL-producing E. coli are sensitive to faropenem (FRPM), there are few clinical studies on the efficiency of FRPM against acute cystitis caused by the bacteria. Therefore, we retrospectively reviewed the medical charts of patients with acute cystitis caused by ESBL-producing E. coli who were treated with the oral antimicrobial agent faropenem (FRPM) in our institution from June 2011 to May 2015. Ten patients with acute cystitis caused by ESBL producing E. coli were treated with FRPM. Although clinical cure was achieved in 9 of them, it reoccurred in 3. This study revealed that the treatment regimen with FRPM for patients with acute cystitis caused by ESBL-producing E. coli is promising. However, a non-negligible number of recurrences were caused by ESBL-producing E. coli because of the nature of underlying diseases or pathologies in the urinary tract.

Soleal vein dilatation assessed by ultrasonography is an independent predictor for deep vein thrombosis after major orthopedic surgery.

Kiyoshi Abe, Satoshi Yuda, Kenji Yasui, Ayumi Okubo, Chihiro Kobayashi, Atsuko Muranaka, Hirofumi Ohnishi, Akiyoshi Hashimoto, Atsushi Teramoto, Satoshi Nagoya, Kazufumi Tsuchihashi, Toshihiko Yamashita, Satoshi Takahashi, Tetsuji Miura

Journal of cardiology 69 ( 5 ) 756 - 762 2017年05月 [国際誌]

BACKGROUND: Deep vein thrombosis (DVT) develops after major orthopedic surgery despite the current use of prophylaxis. DVT frequently develops in the soleal vein (SV) and might develop easily at the site of SV dilatation because of blood flow stasis. However, whether preoperative SV dilatation detected by ultrasonography predicts DVT after major orthopedic surgery remains unknown. OBJECTIVE: We examined whether SV dilatation detected by preoperative ultrasonography predicts DVT after major orthopedic surgery. METHODS: Ultrasonography was performed preoperatively and postoperatively in 243 patients with orthopedic diseases (mean age of 67±13 years, 77% women) who underwent total hip arthroplasty (THA, n=180) or total knee arthroplasty (TKA, n=63). Presence of DVT was diagnosed by ultrasonography and SV diameter ≥10mm was defined as SV dilatation. Patients with preoperative DVT were excluded. RESULTS: Sixty-nine patients (28%) developed postoperative DVT. SV dilatation was found in 24 patients (10%), and 16 (67%) of those patients had postoperative DVT. Multivariate logistic regression analysis showed that female gender [odds ratio (OR): 4.09, p=0.004], TKA (OR: 2.52, p=0.011), and SV dilatation (OR: 6.67, p<0.001), but not presence of comorbidities, medications, or plasma d-dimer value, independently predict postoperative DVT. Subgroup analyses according to the operation site showed that female gender (OR: 3.27, p=0.043) and SV dilatation (OR: 3.72, p=0.022) were independent predictors of postoperative DVT in the THA group. SV dilatation (OR: 12.0, p=0.027) was an independent predictor of postoperative DVT also in the TKA group. CONCLUSIONS: In addition to gender and TKA, SV dilatation detected by ultrasonography is an independent predictor of DVT after major orthopedic surgery. Determination of SV diameter by ultrasonography before major orthopedic surgery is useful for assessing the risk of postoperative DVT.

Serotype distribution, antimicrobial resistance and prevalence of pilus islets in pneumococci following the use of conjugate vaccines.

Mitsuyo Kawaguchiya, Noriko Urushibara, Meiji Soe Aung, Masaaki Shinagawa, Satoshi Takahashi, Nobumichi Kobayashi

Journal of medical microbiology 66 ( 5 ) 643 - 650 2017年05月 [国際誌]

PURPOSE: In Japan, the 7-valent pneumococcal vaccine (PCV7) was introduced in 2010 and, in 2013, the PCV7 was replaced with the 13-valent pneumococcal vaccine (PCV13). This study was conducted to investigate serotypes, antimicrobial resistance and prevalence of pilus islets in pneumococcal isolates from inpatients in a Japanese tertiary hospital. METHODOLOGY: From April 2011 to February 2016, 151 isolates [95 (18 children, 77 adults) and 56 (19 children, 37 adults) in the PCV7 and PCV13 periods, respectively] were collected. All isolates were serotyped using genetic methods and were tested for susceptibility to 18 antimicrobials. Unaltered penicillin-binding protein (PBP) genes, macrolide resistance genes and pilus islets were identified by PCR. RESULTS: Between the two periods, the prevalence of non-PCV13 serotypes was shown to increase from 50.0 to 78.9 % in children, and serotype 3 increased from 14.3 to 24.3 % in adults. Six of seven isolates from invasive diseases were assigned to non-PCV13 serotypes. Overall, multidrug resistance (MDR) was detected in 46.4 % of isolates, which included the dominant non-PCV13 serotypes 6E, 15A and 23A (prevalence≥75.0 %). gPRSP (three altered genes pbp1a, pbp2b and pbp2x) and macrolide resistance genes [erm(B) and/or mef(A/E)] were detected in 35.8 and 93.4 % of all isolates, respectively. Pilus islets [PI-1 (clade I, II and III) and/or PI-2] were found in 22.5 % (34/151) of isolates belonging to six different serotypes (19F, 23F, 19A, 6E, 15B and 35B) and 88.2 % (30/34) of these exhibited MDR. CONCLUSION: This study revealed the spread of MDR in several non-PCV13 serotypes and in isolates with pilus islets.

Surfactant Protein A Inhibits Growth and Adherence of Uropathogenic Escherichia coli To Protect the Bladder from Infection

Jiro Hashimoto, Motoko Takahashi, Atsushi Saito, Masaki Murata, Yuichiro Kurimura, Chiaki Nishitani, Rina Takamiya, Yasuaki Uehara, Yoshihiro Hasegawa, Yoshiki Hiyama, Norimasa Sawada, Satoshi Takahashi, Naoya Masumori, Yoshio Kuroki, Shigeru Ariki

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 198 ( 7 ) 2898 - 2905 2017年04月 [査読有り]

Surfactant protein A (SP-A) is a multifunctional host defense collectin that was first identified as a component of pulmonary surfactant. Although SP-A is also expressed in various tissues, including the urinary tract, its innate immune functions in nonpulmonary tissues are poorly understood. In this study, we demonstrated that adherence of uropathogenic Escherichia coli (UPEC) to the bladder was enhanced in SP-A-deficient mice, which suggests that SP-A plays an important role in innate immunity against UPEC. To understand the innate immune functions of SP-A in detail, we performed in vitro experiments. SP-A directly bound to UPEC in a Ca2+-dependent manner, but it did not agglutinate UPEC. Our results suggest that a bouquet-like arrangement seems unsuitable to agglutinate UPEC. Meanwhile, SP-A inhibited growth of UPEC in human urine. Furthermore, the binding of SP-A to UPEC decreased the adherence of bacteria to urothelial cells. These results indicate that direct action of SP-A on UPEC is important in host defense against UPEC. Additionally, adhesion of UPEC to urothelial cells was decreased when the cells were preincubated with SP-A. Adhesion of UPEC to urothelial cells is achieved via interaction between FimH, an adhesin located at bacterial pili, and uroplakin Ia, a glycoprotein expressed on the urothelium. SP-A directly bound to uroplakin Ia and competed with FimH for uroplakin Ia binding. These results lead us to conclude that SP-A plays important roles in host defense against UPEC.

Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648.

Toyotaka Sato, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy 61 ( 2 ) 2017年02月 [国際誌]

Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, <0.125 mg/liter) and 194 fluoroquinolone-resistant isolates (CIP MIC, >2 mg/liter). The MIC50 and MIC90 for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC50, 0.5 mg/liter versus 0.25 mg/liter; MIC90, 1 mg/liter versus 0.5 mg/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant/intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.

Analysis of the causes of discrepancies in troponin I concentrations as measured by ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cTnI.

Takashi Kondo, Daisuke Kobayashi, Maki Mochizuki, Kouichi Asanuma, Satoshi Takahashi

Annals of clinical biochemistry 54 ( 1 ) 121 - 126 2017年01月 [国際誌]

Background Recently developed reagents for the highly sensitive measurement of cardiac troponin I are useful for early diagnosis of acute coronary syndrome. However, differences in measured values between these new reagents and previously used reagents have not been well studied. In this study, we aimed to compare the values between ARCHITECT High-Sensitive Troponin I ST (newly developed reagents), ARCHITECT Troponin I ST and STACIA CLEIA cardiac troponin I (two previously developed reagent kits). Methods Gel filtration high-performance liquid chromatography was used to analyse the causes of differences in measured values. Results The measured values differed between ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cardiac troponin I reagents (r = 0.82). Cross-reactivity tests using plasma with added skeletal-muscle troponin I resulted in higher reactivity (2.17-3.03%) for the STACIA CLEIA cardiac troponin I reagents compared with that for the ARCHITECT High-Sensitive Troponin I ST reagents (less than 0.014%). In addition, analysis of three representative samples using gel filtration high-performance liquid chromatography revealed reagent-specific differences in the reactivity against each cardiac troponin I complex; this could explain the differences in values observed for some of the samples. Conclusion The newly developed ARCHITECT High-Sensitive Troponin I ST reagents were not affected by the presence of skeletal-muscle troponin I in the blood and may be useful for routine examinations.

Editorial Comment to Novel algorithm for management of acute epididymitis.

Satoshi Takahashi

International journal of urology : official journal of the Japanese Urological Association 24 ( 1 ) 87 - 88 2017年01月 [国際誌]

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