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Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital
Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo...
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Published in: | BMC infectious diseases 2016-08, Vol.16 (1), p.372-372, Article 372 |
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creator | Kimura, Muneyoshi Araoka, Hideki Yoshida, Atsushi Yamamoto, Hisashi Abe, Masahiro Okamoto, Yuki Yuasa, Mitsuhiro Kaji, Daisuke Kageyama, Kosei Nishida, Aya Ishiwata, Kazuya Takagi, Shinsuke Yamamoto, Go Asano-Mori, Yuki Uchida, Naoyuki Hishinuma, Akira Izutsu, Koji Wake, Atsushi Taniguchi, Shuichi Yoneyama, Akiko |
description | Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking.
The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility.
Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare. |
doi_str_mv | 10.1186/s12879-016-1692-y |
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The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility.
Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/s12879-016-1692-y</identifier><identifier>PMID: 27495798</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Aged ; Antibiotic Prophylaxis - methods ; Bacteremia ; Bacteremia - drug therapy ; Bacteremia - epidemiology ; Bacteremia - microbiology ; Care and treatment ; Complications and side effects ; Diagnosis ; Female ; Hematologic Neoplasms - complications ; Hematologic Neoplasms - epidemiology ; Hematologic Neoplasms - therapy ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hospitals ; Humans ; Infectious diseases ; Japan - epidemiology ; Levofloxacin ; Levofloxacin - therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Stem cells ; Streptococcal infections ; Streptococcal Infections - epidemiology ; Streptococcal Infections - microbiology ; Streptococcal Infections - prevention & control ; Transplantation ; Transplantation Conditioning - methods ; Transplantation, Homologous ; Viridans Streptococci - isolation & purification ; Young Adult</subject><ispartof>BMC infectious diseases, 2016-08, Vol.16 (1), p.372-372, Article 372</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c698t-7384de0ed5b4a973e133f5f2d404224109481164535bf4a820c4f85d69d70bc3</citedby><cites>FETCH-LOGICAL-c698t-7384de0ed5b4a973e133f5f2d404224109481164535bf4a820c4f85d69d70bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975918/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1816990375?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27495798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kimura, Muneyoshi</creatorcontrib><creatorcontrib>Araoka, Hideki</creatorcontrib><creatorcontrib>Yoshida, Atsushi</creatorcontrib><creatorcontrib>Yamamoto, Hisashi</creatorcontrib><creatorcontrib>Abe, Masahiro</creatorcontrib><creatorcontrib>Okamoto, Yuki</creatorcontrib><creatorcontrib>Yuasa, Mitsuhiro</creatorcontrib><creatorcontrib>Kaji, Daisuke</creatorcontrib><creatorcontrib>Kageyama, Kosei</creatorcontrib><creatorcontrib>Nishida, Aya</creatorcontrib><creatorcontrib>Ishiwata, Kazuya</creatorcontrib><creatorcontrib>Takagi, Shinsuke</creatorcontrib><creatorcontrib>Yamamoto, Go</creatorcontrib><creatorcontrib>Asano-Mori, Yuki</creatorcontrib><creatorcontrib>Uchida, Naoyuki</creatorcontrib><creatorcontrib>Hishinuma, Akira</creatorcontrib><creatorcontrib>Izutsu, Koji</creatorcontrib><creatorcontrib>Wake, Atsushi</creatorcontrib><creatorcontrib>Taniguchi, Shuichi</creatorcontrib><creatorcontrib>Yoneyama, Akiko</creatorcontrib><title>Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking.
The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility.
Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibiotic Prophylaxis - methods</subject><subject>Bacteremia</subject><subject>Bacteremia - drug therapy</subject><subject>Bacteremia - epidemiology</subject><subject>Bacteremia - microbiology</subject><subject>Care and treatment</subject><subject>Complications and side effects</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Hematologic Neoplasms - complications</subject><subject>Hematologic Neoplasms - epidemiology</subject><subject>Hematologic Neoplasms - therapy</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Japan - epidemiology</subject><subject>Levofloxacin</subject><subject>Levofloxacin - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Stem cells</subject><subject>Streptococcal infections</subject><subject>Streptococcal Infections - epidemiology</subject><subject>Streptococcal Infections - microbiology</subject><subject>Streptococcal Infections - prevention & control</subject><subject>Transplantation</subject><subject>Transplantation Conditioning - methods</subject><subject>Transplantation, Homologous</subject><subject>Viridans Streptococci - isolation & purification</subject><subject>Young Adult</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNqNkstu1DAUhiMEohd4ADbIEhtYpNixk9gbpFJxKapUCSq2lsc5SVycOLWd0cz79EFxmFI6iAXywsf2d37b5_xZ9oLgE0J49TaQgtcix6TKSSWKfPsoOySsJnlBKXv8ID7IjkK4xpjUvBBPs4OiZqKsBT_Mbt97UD9i793c9WhtvGnUGFCIHqbotNNaWbRSOoKHwShkRqSsdR2MYDTqYVDRTc5ATKsQYUAarEXRJ5HJqjEiD9pMBsYYlhDM2owdsrB2rXUbpZPe5N3Ub63amPBLHn1RkxohAOpdmExU9ln2pFU2wPO7-Ti7-vjh6uxzfnH56fzs9CLXleAxrylnDWBoyhVToqZAKG3LtmgYZkXBCBaME1KxkparlileYM1aXjaVaGq80vQ4e7eTnebVAI1Oj_bKysmbQfmtdMrI_ZPR9LJza8lEXQrCk8DrOwHvbmYIUQ4mLAVJ33FzkIQTTEtKK5HQV3-h1272Y_rdQlVCYFqXf6hOWZBmbF26Vy-i8pRVnKcG8zpRJ_-g0mhSy7QboTVpfy_hzV5CYiJsYqfmEOT5t6__z15-32fJjtXeheChva8dwXJxrNw5VibHysWxcptyXj4s-n3Gb4vSn6176ZI</recordid><startdate>20160805</startdate><enddate>20160805</enddate><creator>Kimura, Muneyoshi</creator><creator>Araoka, Hideki</creator><creator>Yoshida, Atsushi</creator><creator>Yamamoto, Hisashi</creator><creator>Abe, Masahiro</creator><creator>Okamoto, Yuki</creator><creator>Yuasa, Mitsuhiro</creator><creator>Kaji, Daisuke</creator><creator>Kageyama, Kosei</creator><creator>Nishida, Aya</creator><creator>Ishiwata, Kazuya</creator><creator>Takagi, Shinsuke</creator><creator>Yamamoto, Go</creator><creator>Asano-Mori, Yuki</creator><creator>Uchida, Naoyuki</creator><creator>Hishinuma, Akira</creator><creator>Izutsu, Koji</creator><creator>Wake, Atsushi</creator><creator>Taniguchi, Shuichi</creator><creator>Yoneyama, Akiko</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T2</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160805</creationdate><title>Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital</title><author>Kimura, Muneyoshi ; Araoka, Hideki ; Yoshida, Atsushi ; Yamamoto, Hisashi ; Abe, Masahiro ; Okamoto, Yuki ; Yuasa, Mitsuhiro ; Kaji, Daisuke ; Kageyama, Kosei ; Nishida, Aya ; Ishiwata, Kazuya ; Takagi, Shinsuke ; Yamamoto, Go ; Asano-Mori, Yuki ; Uchida, Naoyuki ; Hishinuma, Akira ; Izutsu, Koji ; Wake, Atsushi ; Taniguchi, Shuichi ; Yoneyama, Akiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c698t-7384de0ed5b4a973e133f5f2d404224109481164535bf4a820c4f85d69d70bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibiotic Prophylaxis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kimura, Muneyoshi</au><au>Araoka, Hideki</au><au>Yoshida, Atsushi</au><au>Yamamoto, Hisashi</au><au>Abe, Masahiro</au><au>Okamoto, Yuki</au><au>Yuasa, Mitsuhiro</au><au>Kaji, Daisuke</au><au>Kageyama, Kosei</au><au>Nishida, Aya</au><au>Ishiwata, Kazuya</au><au>Takagi, Shinsuke</au><au>Yamamoto, Go</au><au>Asano-Mori, Yuki</au><au>Uchida, Naoyuki</au><au>Hishinuma, Akira</au><au>Izutsu, Koji</au><au>Wake, Atsushi</au><au>Taniguchi, Shuichi</au><au>Yoneyama, Akiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital</atitle><jtitle>BMC infectious diseases</jtitle><addtitle>BMC Infect Dis</addtitle><date>2016-08-05</date><risdate>2016</risdate><volume>16</volume><issue>1</issue><spage>372</spage><epage>372</epage><pages>372-372</pages><artnum>372</artnum><issn>1471-2334</issn><eissn>1471-2334</eissn><abstract>Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking.
The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility.
Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27495798</pmid><doi>10.1186/s12879-016-1692-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1471-2334 |
ispartof | BMC infectious diseases, 2016-08, Vol.16 (1), p.372-372, Article 372 |
issn | 1471-2334 1471-2334 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4975918 |
source | Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3) |
subjects | Adult Aged Antibiotic Prophylaxis - methods Bacteremia Bacteremia - drug therapy Bacteremia - epidemiology Bacteremia - microbiology Care and treatment Complications and side effects Diagnosis Female Hematologic Neoplasms - complications Hematologic Neoplasms - epidemiology Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation - adverse effects Hospitals Humans Infectious diseases Japan - epidemiology Levofloxacin Levofloxacin - therapeutic use Male Middle Aged Retrospective Studies Stem cells Streptococcal infections Streptococcal Infections - epidemiology Streptococcal Infections - microbiology Streptococcal Infections - prevention & control Transplantation Transplantation Conditioning - methods Transplantation, Homologous Viridans Streptococci - isolation & purification Young Adult |
title | Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T11%3A34%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Breakthrough%20viridans%20streptococcal%20bacteremia%20in%20allogeneic%20hematopoietic%20stem%20cell%20transplant%20recipients%20receiving%20levofloxacin%20prophylaxis%20in%20a%20Japanese%20hospital&rft.jtitle=BMC%20infectious%20diseases&rft.au=Kimura,%20Muneyoshi&rft.date=2016-08-05&rft.volume=16&rft.issue=1&rft.spage=372&rft.epage=372&rft.pages=372-372&rft.artnum=372&rft.issn=1471-2334&rft.eissn=1471-2334&rft_id=info:doi/10.1186/s12879-016-1692-y&rft_dat=%3Cgale_pubme%3EA468814787%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c698t-7384de0ed5b4a973e133f5f2d404224109481164535bf4a820c4f85d69d70bc3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1816990375&rft_id=info:pmid/27495798&rft_galeid=A468814787&rfr_iscdi=true |