Fumiaki Ikeda

LSI Corporation, San José, California, United States

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Publications (67)145.37 Total impact

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    ABSTRACT: The in vitro activity of ravuconazole (RVCZ) was compared with those of itraconazole (ITCZ) and terbinafine (TBF) against 73 dermatophyte isolates and 18 Candida spp. isolates recovered from patients with dermatomycosis at 4 dermatological clinics in Japan in 2011. The dermatophyte isolates consisted of Trichophyton rubrum (n=51), Trichophyton mentagrophytes (n=20 : these strains were not identified by molecular phylogenetic analysis.), Trichophyton tonsurans (n=1), and Microsporum canis (n=1). The Candida spp. isolates comprised C. albicans (n=11), C. parapsilosis (n=5), C. guilliermondii (n=1), and C. pseudohaemulonii (n=1). RVCZ was highly active against all dermatophytes and all Candida spp. : the geometric mean (GM) MICs for T. rubrum and T. mentagrophytes were 0.035 μg/mL and MICs for T. tonsurans and M. canis were ≤ 0.03μg/mL, and GM MICs for C. albicans and C. parapsilosis were ≤ 0.03μg/mL and MICs for C. guilliermondii and C. pseudohaemulonii were 0.25 and ≤ 0.03μg/mL, respectively. Compared to RVCZ, ITCZ showed similar anti-dermatophytic and anti-Candida activities, while TBF had a slightly higher anti-dermatophytic but a markedly lower anti-Candida activity. These results suggest that RVCZ is a potential candidate systemic antifungal therapy against onychomycosis and other dermatomycoses that are refractory to topical antifungal therapy.
    Preview · Article · Jan 2014
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    ABSTRACT: The Centers for Disease Control and Prevention (CDC) now recommend combination therapy with ceftriaxone 250 mg plus azithromycin (AZM) 1 g as a first-line regimen for gonorrhea because the increase of Neisseria gonorrhoeae resistant to multiple antimicrobial agents. However, reports on the in vitro activity of antimicrobial combinations against clinical isolates of N. gonorrhoeae are very rare. In the present study, a checkerboard method was utilized to examine the in vitro activity of ceftriaxone (CTRX), cefodizime (CDZM), spectinomycin (SPCM), or gentamicin (GM) in combination with AZM against 25 clinical isolates of N. gonorrhoeae. The SPCM + AZM combination demonstrated the lowest mean fractional inhibitory concentration index (FICI) of 0.69, followed by the CDZM + AZM combination (mean FICI, 0.75), the CTRX + AZM combination (mean FICI, 0.81), and the GM + AZM combination (mean FICI, 0.83). Additivity/indifference effect was detected for the SPCM + AZM combination, the CDZM + AZM combination, the CTRX + AZM combination, and the GM + AZM combination, against 96 %, 72 %, 92 %, and 100 % of the isolates, respectively. There was no antagonism for any of the antimicrobial combinations against the 25 N. gonorrhoeae isolates. These results suggest that the antimicrobial combinations may be worthy of clinical evaluation as an alternative regimen for gonococcal infections caused by antimicrobial-resistant strains.
    No preview · Article · Apr 2013 · Journal of Infection and Chemotherapy
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    ABSTRACT: Metallo-beta-lactamase (MBL) producing Serratia marcescens isolate was recovered from a study patient in September, 2007 in whom MBL non-producing S. marcescens had been isolated 2 months previously. Two S. marcescens isolates recovered from the study patient showed the same pulsed-field gel electrophoresis (PFGE) pattern. Seven S. marcescens isolates were recovered from other patients in our hospital during August, 2007 and November, 2007. Five of the seven isolates produced MBL. All of the MBL-producing isolates showed the same PFGE pattern and harbored plasmids of the same size and bla(IMP) genes. The bla(IMP) genes were easily transferred to Escherichia coli DH5alpha by transformation of a plasmid purified from the MBL-producing isolate. Those transformation experiments suggested that bla(IMP) genes were encoded by the plasmid. From these observations, it was speculated that the MBL non-producing S. marcescens isolate recovered from the study patient had acquired the plasmid which encoded bla(IMP) genes and a monoclone of MBL-producing S. marcescens spread horizontally in our hospital.
    Preview · Article · Mar 2013 · Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
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    ABSTRACT: A mechanism for the acquisition of high-level echinocandin resistance in Candida glabrata was investigated. FKS mutants were constructed to: determine whether clinically significant micafungin resistance requires a hot-spot mutation in FKS1 and a premature stop codon in FKS2, as was observed in a clinical isolate; select for variants with reduced susceptibility and locate mutations in FKS genes; and assess the roles of FKS1 and FKS2. A panel of FKS mutants was constructed using micafungin-susceptible parents by site-directed mutagenesis. Drug susceptibility, gene expression and glucan synthase activities were compared between mutants. Mutations acquired by selection were identified by DNA sequence analysis of FKS genes from selected variants. Single FKS deletants were constructed and their phenotypes examined. Introduction of the hot-spot mutation in FKS1 alone conferred an intermediate reduction in susceptibility, and the premature stop codon in FKS2 alone had no effect on susceptibility, while severely reduced susceptibility equivalent to that of the clinical isolate required both mutations. Exposure of susceptible strains to micafungin yielded variants with an intermediate reduction in susceptibility that possessed a hot-spot mutation in FKS1. Further exposure to micafungin yielded variants with severely reduced susceptibility that acquired various single mutations in FKS2. The phenotypes of Δfks1 and Δfks2 mutants indicate that the two FKS genes are functionally redundant, while deletion of both FKS1 and FKS2 conferred synthetic lethality. In the laboratory mutants of C. glabrata, clinically significant reduced susceptibility to micafungin required single nucleotide changes in both FKS1 and FKS2, and both genes encoded β-1,3-glucan synthase catalytic subunits.
    Full-text · Article · Apr 2012 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: The antimicrobial susceptibility of 93 Acinetobacter baumannii complex isolates from clinical specimens collected nationwide between May and October 2009 were measured by microdilution antimicrobial susceptibility testing based on CLSI M100-S20. Beta-lactamase genes, including classes B and D and ISAbal in meropenem nonsusceptible, including intermediate or resistant isolates, were detected using PCR. Rates of isolates nonsusceptible to meropenem were 18%, to ciprofloxacin 41% and to amikacin 14%. L7-L8: The rate of multidrug-resistant Acinetobacter (MDRA) isolates which were resistant to all 3 antimicrobial agents was 4.3%. MDRA isolates were classified into ST92 by multilocus sequence typing. No metallo-beta-lactamase producer was seen among the 17 meropenem nonsusceptible isolates. The blaoxa-51-like carbapenemase gene and ISAbal were detected in all 17 isolates. ISAba1 upstream presence of the blaOXA-51-like gene was observed in 7 of 17 isolates and the blaOXA-23 like gene in 5 of 17. Consistent with overseas reports, our results confirm the existence of MDRA isolates and isolates harboring OXA carbapenemase genes in Japan. While resistance rates were lower than reports elsewhere, it is clear that resistance trends must be carefully monitored.
    No preview · Article · Sep 2011 · Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
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    ABSTRACT: In a nationwide antimicrobial susceptibility survey of 494 Nesseria gonorrhoeae isolates collected from February 2008 to December 2009 in 3 regions of Japan, 112 (22.7%) were collected from western Japan (Kinki, Chugoku, Shikoku, and Kyushu), 277 (56.1%) from mid-eastern Japan (Kanto), and 105 (21.1%) from eastern Japan (Tokai, Hokuriku, Koushinetsu, Tohoku, and Hokkaido). Resistance to ciprofloxacin (CPFX) was 72.8%, to penicillin G (PCG) 19.8%, and to tetracycline (TC) 18.2%. Intermediate resistance to CPFX was 1.8%, to PCG 73.7%, and to TC 43.7%. These results indicate that both types of resistance to the 3 agents were very high. Intermediate resistance to cefixime (CFIX) was 38.1% and to cefozidim (CDZM) 13.4%. Resistance to CFIX was only 0.4% and to CDZM 0%. Susceptibility to azithromycin was 96.6%, to ceftriaxone 99.8%, and to spectinomycin 100%. No significant difference in resistance was seen to different antimicrobial agent classes tested in the 3 regions, although intermediate resistance to CFIX in western Japan was significantly higher than in mid-eastern Japan.
    Preview · Article · Jul 2011 · Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
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    ABSTRACT: A high rate of resistance (49.5 to 72.7%) to amoxicillin (AMX) was observed in Helicobacter pylori after two or three unsuccessful eradication attempts. Unsuccessful eradication regimens significantly increase resistance to not only clarithromycin (CLR) and metronidazole (MNZ) but also AMX.
    Full-text · Article · Jun 2011 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Purpose: The purpose of the study was to establish the response evaluation criteria of antifungal agents for oral candidiasis. Methods: A multicenter open-label trial was conducted. The patients with oral candidiasis were treated by an antifungal agent, itraconazole, and the response to the agent was evaluated according to the protocoL A multiple regression analysis was employed to examine the relative contribution of clinical signs and symptoms, including redness, white papules, atrophy of the papilla of the tongue, pain and soreness to the global evaluation of the responses judged by the attending physician. The global evaluation of the responses was rated as markedly improved, moderately improved or unchanged. Results: The multiple regression analysis showed that redness of the tongue and palate, white papules on the tongue, atrophy of the papillae of the tongue, and pain were associated with the global evaluation of the responses judged by the attending physician. Conclusion: Evaluation of these signs and symptoms could provide useful response information about antifungal therapy for oral candidiasis patients. Further studies will therefore be needed to verify the results of the present study.
    No preview · Article · Apr 2011
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    ABSTRACT: Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori.
    No preview · Article · Jan 2011 · Biochemical and Biophysical Research Communications
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    ABSTRACT: In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2009, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms was available for the susceptibility testing using the microbroth dilution methods recommended by Clinical Laboratory Standard Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.06 microg/mL for methicillin-susceptible Staphylococcus aureus and was equal to that of garenoxacin (GRNX), 2 times lower than that of moxifloxacin (MFLX), and 8 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90s of STFX ranged from 0.03 to 0.06 microg/mL and were 1 to 2 times lower than those of GRNX, 2 to 4 times lower than those of MFLX, and 16 to 32 times lower than those of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 0.25 microg/mL for Enterococcus faecalis, and was 2 times lower than those of GRNX and MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX for E. coli was 2 microg/mL, and the MIC90s of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 8 microg/mL and was 16 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P aeruginosa isolates recovered from respiratory infections was 2 microg/mL and was 32 times lower than those of GRNX and MFLX, and 16 times lower than that of LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 2 to 4 times lower than those of GRNX, 8 times lower than those of MFLX, and 4 times lower than those of LVFX. The MIC90 of STFX was 0.008 microg/mL for Moraxella catarrhalis, and was 2 times lower than that of GRNX, 8 times lower than those of MFLX and LVFX. The MIC90s of STFX ranged from 0.015 to 0.12 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.
    No preview · Article · Dec 2010 · The Japanese journal of antibiotics
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    ABSTRACT: In recent years, increased isolation of extended-spectrum beta-lactamase (ESBL)-producing Proteus mirabilis has been reported in Japan. We undertook an investigation to determine the prevalence of ESBL-producing P. mirabilis isolated in Japan and to characterise the genotype. Seventy-four P. mirabilis isolates recovered from specimens at 54 hospitals in Japan between March and October 2006 were included in the study. Of the 74 P. mirabilis isolates examined, 28 (37.8%) were ESBL-producers. The bla(CTX-M-2) gene was found in 27 isolates, whilst 1 isolate possessed bla(CTX-M-3). Amongst the 28 ESBL-producers, 25 (89.3%) were non-susceptible to ciprofloxacin, whilst 11 (23.9%) of 46 ESBL-non-producing isolates were non-susceptible to ciprofloxacin. Pulsed-field gel electrophoresis (PFGE) analysis of the 28 ESBL-producing isolates from 19 hospitals revealed 17 clusters. The same PFGE type was observed in two or more hospitals especially in the greater Tokyo area, suggesting possible clonal spread and the need for monitoring to determine whether emergence of a dominant clone occurs. Our results show that in Japan there is a high prevalence of CTX-M-type beta-lactamase-producing P. mirabilis. Moreover, these isolates are characterised by reduced susceptibility to fluoroquinolones.
    No preview · Article · Oct 2010 · International journal of antimicrobial agents
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    ABSTRACT: We report the appearance of Candida glabrata strains with reduced sensitivity during treatment with the echinocandin drug micafungin (MCF). Four C. glabrata strains were isolated from sputum, gastric juice, and blood taken from a patient during hospitalization. Two of these strains, one of which was obtained after treatment with MCF for suspected Candida pneumonia and the other of which was obtained during MCF treatment for candidemia, were isolated from blood and found to have a reduced susceptibility to MCF. These two clinical isolates showed a high minimum inhibitory concentration (MIC) for MCF, with this change in MIC being unique for MCF among established antifungal drugs. To further investigate the mechanism underlying this reduced sensitivity, an in vivo mouse infection model and in vitro enzymatic analysis were performed. MCF had little effect in the mouse disseminated infection model and enzymatic analysis showed the low affinity of MCF to the 1,3-Beta-D-glucan synthase of the clinical isolates, although the enzymes of both clinical isolates and control strain were noncompetitively inhibited by MCF. Taken together, this low affinity of MCF for the enzymes is likely to cause the reduced sensitivities. These data further indicate that MCF could induce acquired MCF-resistant strains during clinical use.
    Full-text · Article · Sep 2010
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    ABSTRACT: Laboratory-derived resistant strains were obtained by serial passage of Streptococcus pneumoniae and Haemophilus influenzae ATCC strains and clinical isolates on agar containing increasing concentrations of ceftriaxone(CTRX) and other β-lactam antibiotics. Ten strains of S. pneumoniae and 10 strains of H. influenzae were subcultured 10 times on agar media containing β-lactam antibiotics at gradually higher concentrations. CTRX MICs and antibiotics used for acquired strain resistance before and after exposure to antibiotics were determined. PBPs gene mutations before and after antibiotic exposure was estimated. An increase of 4 times or more in MIC was observed in 10 strains of S. pneumoniae - strains numbered 4 each for amoxicillin and cefotiam, 3 each for cefotaxime, CTRX, and cefditoren and 2 for panipenem. An increase in MIC of 8 times or more was observed in 10 strains of H. influenzae - strains numbered 7 for CTX, 6 for CDTR, 4 for CTM, 2 for meropenem, 1 each for CTRX and amoxicillin/clavulanic acid. The increase in CTRX MICs was low for strains for which MICs of each antibiotic increased. No differences were seen in the PBPs gene before and after exposure to antibiotics, except for part of strains, suggesting that other resistance mechanisms of participate in resistance.
    No preview · Article · Jul 2010 · Japanese Journal of Chemotherapy
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · May 2010 · ChemInform
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Apr 2010 · ChemInform
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    ABSTRACT: To determine the mechanism of intermediate- and high-level echinocandin resistance, resulting from heterozygous and homozygous mutations in GSC1 (FKS1), in both laboratory-generated and clinical isolates of Candida albicans. The DNA sequences of the entire open reading frames of GSC1, GSL1 (FKS3) and RHO1, which may contribute to the beta-1,3-glucan synthase of a micafungin-susceptible strain and a resistant clinical isolate, were compared. A spontaneous heterozygous mutant isolated by selection for micafungin resistance, and a panel of laboratory-generated homozygous and heterozygous mutants that possessed combinations of the echinocandin-susceptible and -resistant alleles, or mutants with individual GSC1 alleles deleted, were used to compare levels of echinocandin resistance and inhibition of glucan synthase activity. DNA sequence analysis identified a mutation, S645P, in both alleles of GSC1 from the clinical isolate. GSL1 had two homozygous amino acid changes and five non-synonymous nucleotide polymorphisms due to allelic variation. The predicted amino acid sequence of Rho1p was conserved between strains. Reconstruction of the heterozygous (S645/S645F) and homozygous (S645F/S645F) mutation showed that the homozygous mutation conferred a higher level of micafungin resistance (4 mg/L) than the heterozygous mutation (1 mg/L). Exposure of the heterozygous mutant to micafungin resulted in a loss of heterozygosity. Kinetic analysis of beta-1,3-glucan synthase activity showed that the homozygous and heterozygous mutations gave echinocandin susceptibility profiles that correlated with their MIC values. A homozygous hot-spot mutation in GSC1, caused by mutation in one allele and then loss of heterozygosity, is required for high-level echinocandin resistance in C. albicans. Both alleles of GSC1 contribute equally and independently to beta-1,3-glucan synthase activity.
    No preview · Article · Mar 2010 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Sitafloxacin showed MICs of less than or equal to 0.5 μg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.
    Preview · Article · May 2009 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: As the most common cause of neonatal sepsis, Lancefield Group B Streptococcus (GBS) must be diagnosed as early as possible in pregnant women is prevent neonatal infection. A selective enrichment broth medium has been widely recommended to optimally recover GBS from genital and anorectal samples. To establish a culture suitable for screening vaginal swab specimens, we compared subcultures of three selective enrichment media to direct culture on agar medium. Vaginal swab samples were inoculated directly onto 5% sheep blood agar and into New Granada medium (Eiken), Lim broth (Becton, Dickinson, and Company), and Todd Hewitt broth with gentamicin and nalidixic acid (Becton, Dickinson, and Company, Todd). Of the 288 specimens tested, GBS was recovered from 43 samples (14.9%) on direct agar media, with 82 (28.5%), positive on New Granada medium subculture, 67 (23.3%) on Lim broth subculture, and 61 (21.2%) on Todd, subculture. These results demonstrates that selective enrichment broth media provides more superior sensitivity than direct agar media for detection of GBS colonization in vaginal specimens, underscoring the usefulness of selective enrichment broth media in GBS screening for vaginal swabs in pregnant woman.
    No preview · Article · Feb 2009 · Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
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    ABSTRACT: Of 49,998 blood specimens (24,999 cases) collected from hospitals in Japan between 2005 and 2006 and cultured, 207 from 148 cases were positive for Pseudomonas aeruginosa. The susceptibility of these isolates to antibacterial agents were examined. Resistance calculated based on Clinical and Laboratory Standard Institute break points was as follows: amikacin, 3.4%; piperacillin, tazobactam/piperacillin, meropenem, ceftazidime, and ciprofloxacin, 10.8-20.3%; and imipenem, 31.1%. Multidrug-resistant P. aeruginosa (MDRP) was detected in 6 of the 148 cases whose blood specimens were positive for P. aeruginosa. The production of metallo β-lactamase was detected in 4 of 6 MDRP isolates. P. aeruginosa was isolated in clinical specimens other than blood of 55 cases whose blood specimens were positive for the same species. Isolates from clinical specimens other than blood tended to be more resistant to antibacterial agents than isolates from blood specimens. Clinical specimens other than blood of patients whose blood were positive for P. aeruginosa must thus be cultured so that appropriate treatment is provided and to better understand the microbiological characteristics and epidemiology of P. aeruginosa isolates from blood.
    No preview · Article · Jan 2009
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    ABSTRACT: Background: Sitafloxacin is a recently developed fluoroquinolone with wide spectrum activity ranging from gram positive cocci to gram negative bacilli. We studied the influence of mutations in the QRDR of gyrA of Helicobacter pylori on the antimicrobial activity of sitafloxacin (STFX). Methods: A total of 105 H. pylori isolates recovered from patients with peptic ulcer in Japan between 2004 and 2005 were screened for susceptibility to STFX and levofloxacin (LVFX) by agar dilution method according to CLSI guidelines. The QRDR of gyrA was amplified by PCR and the amplicon was sequenced. The sequences were compared to the wild type strain. Results: STFX exhibited excellent antibacterial activity against 105 H. pylori isolates with all isolates having a MIC less of than 0.5 μg/mL. Compared to LVFX, the activity of STFX was 8 to 32-fold greater. Of the 105 H. pylori isolates examined, mutations in the QRDR of gyrA were observed in 44 isolates. Of these isolates, the STFX MIC50 and MIC90 were 0.12 μg/mL and 0.25 μg/mL, respectively, which represents 32 to 64-fold greater activity compared to LVFX. Of the 44 isolates with mutations in the gyrA, the following changes were observed: Asn87 to Lys or Ile (14 isolates); Asp91 to Gly, Tyr or Asn (25 isolates); multiple mutations involving Asn87 or Asp91 and another region (7 isolates). With respect to mutations involving Asn87 and Asp91, the mean LVFX MIC was 9.75 μg/mL and 3.89 μg/mL, respectively, compared to 0.19 and 0.11 μg/mL, respectively, for STFX. Conclusions: STFX in comparison to other fluoroquinolones is less affected by gyrA mutations and exhibits superior MICs even in the presence of mutations. Our data suggests that STFX may be an effective antibiotic in H. pylori eradication therapy.
    No preview · Conference Paper · Oct 2008

Publication Stats

1k Citations
145.37 Total Impact Points

Institutions

  • 2014
    • LSI Corporation
      San José, California, United States
  • 2009-2013
    • Toho University
      • Department of Infection Control and Prevention
      Edo, Tōkyō, Japan
  • 2006
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
  • 2001
    • Nagasaki University
      Nagasaki, Nagasaki, Japan