2007 Fiscal Year Final Research Report Summary
Study of isolation of antimicrobial-resistant Neisseria gonorrhoeae and treatment for infection with antimicrobial-resistant N. gonorrhoeae strain
Project/Area Number |
17591707
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
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Research Institution | Fukuoka University |
Principal Investigator |
TANAKA Masatoshi Fukuoka University, Faculty of Medicine, Professor (30171797)
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Project Period (FY) |
2005 – 2007
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Keywords | Neisseria gonorrhoeae / Antimicrobial resistance / Quinolone resistance / Multidrug resistance / Combination therapy / Azithromycin / penA gene / Penicillin-binding protein 2 |
Research Abstract |
1. Antimicrobial resistance of Neisseria gonorrhoeae: To assess the antimicrobial resistance in Neisseria gonorrhoeae isolated from 2004 through 2006, susceptibility testing was conducted on 644 isolates of the organisms. The proportions of ciprofloxacin (CPFX)-resistant isolates, penicillin (PCG)-resistant isolates, tetracycline (TC)-resistant isolates, and intermediately cefixime-resistant isolates in 2004-2006 were 4.6〜5.3 folds, 2.7〜3.4 folds, 11.6〜31.1 folds, and 8.4〜19.9 folds higher than those of the isolates in 1995-1996, respectively. Moreover, the proportions of isolates resistant to 2 or 3 among the 3 drugs of CPFX, PCG, and TC increased. 2. In vitro synergistic effects of double combinations of β-lactams and azithromycin: In this study, a checkerboard method was utilized to investigate the in vitro activities of cefixime (CFIX), cefteram (CFTM), or amoxicillin (AMPC) in combination with azithromycin (AZM) against 25 clinical isolates of N. gonorrhoeae. Synergy+partial syner
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gy was observed in 76% of CFIX+AZM (median FIC index:0.53), 80% of CFTM+AZM (median FIC index:0.63), and 56% of AMPC+AZM (median FIC index: 0.75). This study demonstrated that the in vitro activity of β-lactams against N. gonorrhoeae can be enhanced in combination with AZM. 3. Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype: A Neisseria gonorrhoeae strain with a reduced susceptibility to ceftriaxone (MIC=0.5μg/mL) was isolated in Fukuoka city. The N. gonorrhoeae strain was negative for penicillinase production but it showed multidrug resistance against PCG, TC, AZM and CPFX. The N. gonorrhoeae strain contained a significantly different sequence of the penA gene from that of the ceftriaxone-susceptible strains. Some regions of the transpeptidase domain within this penA gene were closely similar to those found in other Neisseria species such as Neisseria subflava. This strain also included a ponA mutation that is associated with a high-level resistance to penicillin. Less
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