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多剤耐性肺炎球菌による呼吸器感染症および耳鼻咽喉科領域感染症に対するgarenoxacinの臨床効果


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Title: 多剤耐性肺炎球菌による呼吸器感染症および耳鼻咽喉科領域感染症に対するgarenoxacinの臨床効果
Other Titles: Clinical response of garenoxacin against respiratory tract infection and otorhinolaryngological infection caused by multidrug-resistant Streptococcus pneumoniae
Authors: 河野, 茂 / 小林, 宏行 / 馬場, 駿吉 / 高畑, 正裕
Authors (alternative): Kohno, Shigeru / Kobayashi, Hiroyuki / Baba, Shunkichi / Takahata, Masahiro
Issue Date: Oct-2007
Publisher: 日本化学療法学会 / Japanese Society of Chemotherapy
Citation: 日本化学療法学会雑誌, 55(S1), pp.222-230; 2007
Abstract: 新規な経口デスフルオロキノロン系抗菌薬であるgarenoxacin mesilate hydrate(GRNX)の呼吸器感染症および耳鼻咽喉科領域感染症を対象とした臨床試験(8試験)から,Streptococcus pneumoniaeを原因菌とする症例を対象として,原因菌の各種抗菌薬に対する感受性を測定し,多剤耐性肺炎球菌の同定,penicillin binding protein(PBP)遺伝子変異およびマクロライド耐性遺伝子の解析を行い,S. pneumoniaeの耐性別に臨床効果を検討した。GRNXが投与された症例から原因菌として130株のS. pneumoniaeが分離され,このうちpenicillin-resistant S. pneumoniae(PRSP)が20.8%(27/130株)およびpenicillin-intermediate resistant S. pneumoniae(PISP)が26.2%(34/130株)と判定された。各種抗菌薬に対する耐性度を検討するために,106株について再度感受性を測定した。S. pneumoniaeに対する各種抗菌薬のMIC90は,GRNX 0.125 μg/mL,levofloxacin 2 μg/mL,gatifloxacin 0.5 μg/mL,moxifloxacin 0.25 μg/mL,cefuroxime 8 μg/mL,erythromycin>128 μg/mL,azithromycin>128 μg/mL,telithromycin 0.25 μg/mL,tetracycline 64 μg/mLおよびsulfamethoxazole-trimethoprim(ST)2 μg/mLであり,GRNXは測定した薬剤のなかで最も強い抗菌活性を示した。各抗菌薬に対する耐性菌の頻度はキノロン耐性2.8%(3/106株),β-ラクタム耐性44.3%(47/106株),マクロライド耐性79.2%(84/106株),テトラサイクリン耐性80.2%(85/106株)およびST耐性9.4%(10/106株)であり,2薬剤以上の多剤耐性菌は78.3%(83/106株)であった。GRNXの投与の有無にかかわらず,臨床試験から分離されたすべてのPRSPおよびPISP 72株におけるPBP遺伝子変異ではpbp1a+pbp2x+pbp2b変異が39株と最も多く,マクロライド耐性遺伝子ではermBが33株と最も多く占めていた。GRNXは,肺炎球菌感染症全体に対する臨床的有効率は96.2%(102/106例)であったが,多剤耐性肺炎球菌に対する有効率が96.4%(80/83例),菌消失率が100%(81/81株)と高い臨床効果であった。 / Subjects with infection caused by Streptococcus pneumoniae were chosen from eight studies of garenoxacin mesilate hydrate(GRNX), a novel oral des-fluoroquinolone, for treatment against respiratory tract infection and otorhinolaryngological infection. Susceptibility to antimicrobial agents, gene analysis of penicillin binding protein(PBP) mutation and macrolide-resistant genes, and clinical response against multidrug-resistant S. pneumoniae were evaluated for subjects. In 130 S. pneumoniae isolates as causative organisms from subjects treated by GRNX, the incidence of penicillin-resistant S. pneumoniae(PRSP) and penicillin-intermediate resistant S. pneumoniae(PISP) were 20.8% (27/130) and 26.2% (34/130). 106 S. pneumoniae susceptibility tests were redone to examine the degree of resistance to antimicrobial agents. MIC90 values of antimicrobial agents against 106 S. pneumoniae were 0.125 μg/mL for GRNX, 2 μg/mL for levofloxacin, 0.5 μg/mL for gatifloxacin, 0.25 μg/mL for moxifloxacin, 8 μg/mL for cefuroxime, >128 μg/mL for erythromycin, >128 μg/mL for azithromycin, 0.25 μg/mL for telithromycin, 64 μg/mL for tetracycline and 2 μg/mL for sulfamethoxazole-trimethoprim(ST). Among these antimicrobial agents, GRNX showed the strongest activity. In 106 S. pneumoniae isolates, 2.8% (3/106) were quinolone-resistant, 44.3% (47/106) were β-lactam-resistant, 79.2% (84/106) were macrolide-resistant, 80.2% (85/106) were tetracycline-resistant, 9.4% (10/106) were ST resistant, and 78.3% (83/106) were multidrug-resistant. In the 72 isolates of PRSP and PISP isolated from all clinical studies in spite of GRNX treatment/notreatment, pbp1a+pbp2x+pbp2b mutation (39/72) regarding PBP and ermB presence (33/72) regarding the macrolide-resistant gene were observed most frequently. Against infections caused by multidrug-resistant S. pneumoniae, GRNX showed good clinical response as 96.4% (80/83) for clinical efficacy and 100% (81/81) for bacterial eradication.
Keywords: garenoxacin / des-fluoro(6)-quinolone / multidrug-resistant Streptococcus pneumoniae
URI: http://hdl.handle.net/10069/26671
ISSN: 13407007
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/26671

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