47 results on '"Yamaguchi, K."'
Search Results
2. Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice
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Matsumoto, T, primary, Tateda, K, additional, Miyazaki, S, additional, Furuya, N, additional, Ohno, A, additional, Ishii, Y, additional, Hirakata, Y, additional, and Yamaguchi, K, additional
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- 1997
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3. Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin
- Author
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Tateda, K, primary, Ishii, Y, additional, Matsumoto, T, additional, Furuya, N, additional, Nagashima, M, additional, Matsunaga, T, additional, Ohno, A, additional, Miyazaki, S, additional, and Yamaguchi, K, additional
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- 1996
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4. Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of antibiotics in this model
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Tateda, K, primary, Takashima, K, additional, Miyazaki, H, additional, Matsumoto, T, additional, Hatori, T, additional, and Yamaguchi, K, additional
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- 1996
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5. In vitro and in vivo antibacterial activities of S-1090, a new oral cephalosporin
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Tsuji, M, primary, Ishii, Y, additional, Ohno, A, additional, Miyazaki, S, additional, and Yamaguchi, K, additional
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- 1995
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6. In vitro and in vivo antibacterial activities of BO-2727, a new carbapenem
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Asahi, Y, primary, Miyazaki, S, additional, and Yamaguchi, K, additional
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- 1995
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7. In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives
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Fujii, K, primary, Tsuji, A, additional, Miyazaki, S, additional, Yamaguchi, K, additional, and Goto, S, additional
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- 1994
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8. Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa
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Mizukane, R, primary, Hirakata, Y, additional, Kaku, M, additional, Ishii, Y, additional, Furuya, N, additional, Ishida, K, additional, Koga, H, additional, Kohno, S, additional, and Yamaguchi, K, additional
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- 1994
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9. Effects of sub-MICs of erythromycin and other macrolide antibiotics on serum sensitivity of Pseudomonas aeruginosa
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Tateda, K, primary, Hirakata, Y, additional, Furuya, N, additional, Ohno, A, additional, and Yamaguchi, K, additional
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- 1993
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10. In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin
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Toyosawa, T, primary, Miyazaki, S, additional, Tsuji, A, additional, Yamaguchi, K, additional, and Goto, S, additional
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- 1993
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11. Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa
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Hirakata, Y, primary, Kaku, M, additional, Mizukane, R, additional, Ishida, K, additional, Furuya, N, additional, Matsumoto, T, additional, Tateda, K, additional, and Yamaguchi, K, additional
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- 1992
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12. Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice
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Hirakata, Y, primary, Kaku, M, additional, Tomono, K, additional, Tateda, K, additional, Furuya, N, additional, Matsumoto, T, additional, Araki, R, additional, and Yamaguchi, K, additional
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- 1992
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13. In vitro and in vivo antibacterial activities of a new quinolone, OPC-17116
- Author
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Imada, T, primary, Miyazaki, S, additional, Nishida, M, additional, Yamaguchi, K, additional, and Goto, S, additional
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- 1992
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14. Antiviral activity of sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325)
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Ohnishi, H, Yamaguchi, K, Shimada, S, Himuro, S, and Suzuki, Y
- Abstract
Sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325) was evaluated for antiviral activity in tissue culture and infected mice. At concentrations ranging from 2.5 to 75.8 micrograms/ml, M12325 inhibited the cytopathic effects of 10 mean tissue culture infective doses of influenza virus A/WSN, A/FM, A/Kumamoto, and B/Great Lakes; parainfluenza virus; rhinovirus; echovirus; respiratory syncytial virus; and vesicular stomatitis virus. Concentrations up to 150 micrograms/ml did not inhibit the cytopathic effects of herpes simplex virus, vaccinia virus, or adenovirus. Concentrations up to 3,160 micrograms/ml did not inhibit the growth of MDCK, Vero, or HEL cells in culture. Single oral doses of M12325, ranging from 10 to 300 mg/kg, administered 1 h before and 1 h after challenge, reduced mortality in mice inoculated intranasally with influenza A/WSN virus. Twice daily oral doses for 14 days effected significant reductions in the mortality of mice infected intranasally with influenza A/WSN, A/FM, A/Kumamoto, and B/Great Lakes, and parainfluenza virus, but they were not effective in mice infected with herpes simplex virus. Multiple doses of 10 and 30 mg/kg, administered intraperitoneally, reduced lung consolidation and virus titer. M12325 was well tolerated in multiple doses up to 1 g/kg orally. These observations support the conclusions that M12325 has a broad spectrum of activity against RNA viruses in vitro and in vivo, selective toxicity, and a large margin of safety.
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- 1982
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15. Efficacy of NY-198 against experimental Legionnaires disease
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Kohno, S, primary, Yamaguchi, K, additional, Dohtsu, Y, additional, Koga, H, additional, Hayashi, T, additional, Hirota, M, additional, Saito, A, additional, and Hara, K, additional
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- 1988
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16. Factors Associated with Breakthrough Fungemia Caused by Candida , Trichosporon , or Fusarium Species in Patients with Hematological Disorders.
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Kimura M, Asano-Mori Y, Sakoh T, Abe M, Ueno K, Hoshino Y, Nakamura S, Umeyama T, Yamagoe S, Miyazaki Y, Baba M, Okada C, Ogura S, Mitsuki T, Yamaguchi K, Yuasa M, Kaji D, Kageyama K, Nishida A, Taya Y, Ishiwata K, Takagi S, Yamamoto H, Yamamoto G, Uchida N, Wake A, Taniguchi S, and Araoka H
- Subjects
- Adult, Antifungal Agents therapeutic use, Candida, Humans, Middle Aged, Candidemia drug therapy, Cryptococcus neoformans, Fungemia drug therapy, Fungemia microbiology, Fusarium, Hematologic Diseases complications, Hematologic Diseases drug therapy, Trichosporon
- Abstract
Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years ( P = 0.011), chronic renal failure ( P = 0.0087), septic shock ( P < 0.0001), steroid administration ( P = 0.0085), and liposomal amphotericin B breakthrough fungemia ( P = 0.0011). An absolute neutrophil count of >500/μL was significantly more common in candidemia in the multivariate analysis ( P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia ( P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia ( P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.
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- 2022
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17. Clinical and Microbiological Characteristics of Proven Invasive Aspergillosis Due to Rare/Cryptic Species in Allogeneic Hematopoietic Stem Cell Transplant Recipients.
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Yamamuro R, Kimura M, Asano-Mori Y, Abe M, Nakamura S, Umeyama T, Yamagoe S, Miyazaki Y, Ogura S, Sakoh T, Mitsuki T, Yamaguchi K, Yuasa M, Kaji D, Kageyama K, Nishida A, Taya Y, Ishiwata K, Takagi S, Yamamoto H, Yamamoto G, Uchida N, Wake A, Taniguchi S, and Araoka H
- Subjects
- Antifungal Agents therapeutic use, Aspergillus genetics, Humans, Retrospective Studies, Aspergillosis drug therapy, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections drug therapy
- Abstract
There are few reports on the clinical course of proven invasive aspergillosis (IA) due to rare/cryptic species in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. We retrospectively reviewed the electronic medical records of patients who underwent allo-HSCT between January 2012 and December 2018. Of 934 allo-HSCT recipients, 10 were diagnosed with proven IA and 61 were diagnosed with probable IA. DNA sequencing was performed in cases of proven IA, and Aspergillus could be identified to the species level in 8 of the 10 cases. Three were due to A. fumigatus, and 5 were due to rare/cryptic Aspergillus species, namely, A. turcosus , A. felis , A. viridinutans, A. nidulans, and A. calidoustus. In these 8 patients, no patients with IA due to A. fumigatus died, whereas 3 of the 5 with IA due to rare/cryptic species died within 12 weeks. The 2 surviving cases of IA due to rare/cryptic species were treated with surgical resection and antifungal treatment. Susceptibility testing for cryptic species in 4 cases showed an amphotericin B MIC > 1 mg/L in 3 cases, itraconazole MIC > 1 mg/L in 2 cases, and voriconazole MIC > 1 mg/L in 2 cases. In conclusion, more than half of the causative pathogens of proven IA were rare/cryptic species, so it is important to accurately identify the Aspergillus species. In addition, surgical treatment might be an important option in cases of proven IA, given the possibility that the causative organisms are azole-resistant A. fumigatus or rare/cryptic species.
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- 2022
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18. Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases.
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Ito-Horiyama T, Ishii Y, Ito A, Sato T, Nakamura R, Fukuhara N, Tsuji M, Yamano Y, Yamaguchi K, and Tateda K
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- Anti-Bacterial Agents pharmacology, Cephalosporins pharmacology, Drug Stability, Meropenem, Thienamycins chemistry, Thienamycins pharmacology, beta-Lactamases, Anti-Bacterial Agents chemistry, Bacterial Proteins antagonists & inhibitors, Cephalosporins chemistry, Siderophores chemistry
- Abstract
To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies (kcat/Km) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM(-1) s(-1), respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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- 2016
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19. Characterization of qnrB-like genes in Citrobacter species of the American Type Culture Collection.
- Author
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Saga T, Sabtcheva S, Mitsutake K, Ishii Y, Tateda K, Yamaguchi K, and Kaku M
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- Bacterial Proteins genetics, Citrobacter genetics, Humans, Molecular Sequence Data, Plasmids genetics, Sequence Analysis, DNA, Anti-Bacterial Agents pharmacology, Citrobacter classification, Citrobacter drug effects, Drug Resistance, Bacterial genetics, Genes, Bacterial, Quinolones pharmacology
- Abstract
Among five American Type Culture Collection (ATCC) Citrobacter strains, qnrB60 in Citrobacter freundii ATCC 6879, an isolate from the preantibiotic era, and qnrB61 in Citrobacter braakii ATCC 51113(T), a type strain belonging to the C. freundii complex, were identified. Meanwhile, a truncated qnrB-like pseudogene was identified in C. freundii ATCC 8090(T) and ATCC 43864. No qnrB-like sequence was found in Citrobacter koseri ATCC 27028(T). These findings underscore the close relationship between this species and qnrB.
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- 2013
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20. Virulence-suppressing effects of linezolid on methicillin-resistant Staphylococcus aureus: possible contribution to early defervescence.
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Yoshizawa S, Tateda K, Saga T, Ishii Y, and Yamaguchi K
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- Animals, Colony Count, Microbial, Cytokines metabolism, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Female, Humans, Interleukin-6 antagonists & inhibitors, Interleukin-6 biosynthesis, Linezolid, Lung metabolism, Mice, Mice, Inbred BALB C, Microbial Sensitivity Tests, Pyrogens metabolism, Sepsis drug therapy, Sepsis microbiology, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Tumor Necrosis Factor-alpha biosynthesis, Virulence drug effects, Virulence Factors antagonists & inhibitors, Virulence Factors biosynthesis, Acetamides pharmacology, Anti-Bacterial Agents pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus pathogenicity, Oxazolidinones pharmacology
- Abstract
In the present study, immunomodulatory effects of linezolid (LZD) on methicillin-resistance Staphylococcus aureus (MRSA) infections were evaluated. We have retrospectively reviewed treatment effects of LZD on 52 patients with severe MRSA infections. Sixty-four percent of the febrile patients demonstrated significant defervescence within 3 days, despite the presence of positive culture results. We speculated that this finding might be due to early anti-inflammatory effects of LZD, and to investigate this further we initiated in vivo experiments using mice MRSA pneumonia models. Mice were treated with either LZD or vancomycin (VCM) immediately after intranasal administration of MRSA. Bacterial numbers and levels of inflammatory cytokines in the lungs were determined. Although the bacterial burden in the lungs was not apparently different between the two groups, LZD but not VCM treatment significantly reduced induction of inflammatory cytokines in the lungs (P < 0.05). To evaluate whether this anti-inflammatory response was due to suppression of virulence factor expression, filter-sterilized supernatants of MRSA incubated in broth overnight with sub-MICs of LZD were subcutaneously administered to mice. To clarify whether LZD possesses direct host-modulating activity, cytokine responses to the supernatants were examined in mice pretreated with LZD. Interestingly, MRSA solutions prepared in the presence of sub-MICs of LZD revealed significant suppression of interleukin 6 (IL-6) in a dose-dependent manner (P < 0.05), but pretreatment of mice with LZD revealed no changes in cytokines. These findings suggest that sub-MICs of LZD might suppress virulence factors of MRSA, which may be associated with a reduction in endogenous pyrogens. These data may explain at least in part early defervescence observed in LZD-treated individuals.
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- 2012
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21. Chromosomal integration and location on IncT plasmids of the blaCTX-M-2 gene in Proteus mirabilis clinical isolates.
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Harada S, Ishii Y, Saga T, Kouyama Y, Tateda K, and Yamaguchi K
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- Anti-Bacterial Agents pharmacology, DNA, Bacterial genetics, Drug Resistance, Bacterial, Electrophoresis, Gel, Pulsed-Field, Humans, Japan epidemiology, Microbial Sensitivity Tests, Molecular Sequence Data, Proteus Infections epidemiology, Proteus Infections microbiology, Proteus mirabilis drug effects, Proteus mirabilis enzymology, Proteus mirabilis isolation & purification, Sequence Analysis, DNA, Chromosomes, Bacterial genetics, Conjugation, Genetic genetics, Plasmids genetics, Proteus mirabilis genetics, beta-Lactamases genetics
- Abstract
Analysis of five CTX-M-2-producing Proteus mirabilis isolates in Japan demonstrated that bla(CTX-M-2) was located on the chromosome in four isolates and on IncT plasmids in three isolates, including two isolates that also carried the gene on the chromosome. In all four isolates with chromosomal bla(CTX-M-2), ISEcp1 was responsible for the integration of the gene into the chromosome. Three different sites in the P. mirabilis genomic sequence were utilized as integration sites.
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- 2012
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22. Efficacy of human-simulated exposures of tomopenem (formerly CS-023) in a murine model of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infection.
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Sugihara K, Tateda K, Yamamura N, Koga T, Sugihara C, and Yamaguchi K
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- Animals, Carbapenems pharmacokinetics, Humans, Male, Mice, Mice, Inbred ICR, Carbapenems therapeutic use, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus pathogenicity, Pseudomonas Infections drug therapy, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa pathogenicity, Staphylococcal Infections drug therapy
- Abstract
Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of P. aeruginosa with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml. Human-simulated dosing regimens in neutropenic mice were designed to approximate the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T(MIC)) observed with tomopenem at 750 and 1,500 mg given as a 0.5-h infusion three times a day (TID) in humans. As reported previously, there was no difference between the target values of P. aeruginosa and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother. 54:5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic effects against 10 of 11 strains of P. aeruginosa and MRSA with MICs of ≤ 8 μg/ml (f%T(MIC) ≥ 41), and tomopenem at 1,500 mg showed bactericidal effects against 16 of 17 strains of P. aeruginosa and MRSA with MICs of ≤ 16 μg/ml (f%T(MIC) ≥ 43). Meropenem at 1,000 mg TID was tested for comparison purposes and showed bactericidal or bacteriostatic effects against 3 of 4 strains of P. aeruginosa with MICs of ≤ 4 μg/ml (f%T(MIC) ≥ 33). From these results, tomopenem is expected to be effective with an f%T(MIC) of over 40 against P. aeruginosa and MRSA strains with MICs of ≤ 8 μg/ml at doses of 750 mg TID and strains with MICs of ≤ 16 μg/ml at doses of 1,500 mg TID.
- Published
- 2011
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23. In vitro intracellular activity and in vivo efficacy of modithromycin, a novel bicyclolide, against Legionella pneumophila.
- Author
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Sato T, Tateda K, Kimura S, Ishii Y, and Yamaguchi K
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- Animals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Azithromycin pharmacology, Azithromycin therapeutic use, Cell Line, Cells, Cultured, Clarithromycin pharmacology, Clarithromycin therapeutic use, Disease Models, Animal, Humans, Ketolides pharmacology, Ketolides therapeutic use, Legionella pneumophila pathogenicity, Legionnaires' Disease drug therapy, Legionnaires' Disease microbiology, Levofloxacin, Mice, Microbial Sensitivity Tests, Ofloxacin pharmacology, Ofloxacin therapeutic use, Bridged-Ring Compounds chemistry, Bridged-Ring Compounds pharmacology, Legionella pneumophila drug effects, Macrolides chemistry, Macrolides pharmacology
- Abstract
The in vitro and in vivo activities of modithromycin, a novel bicyclolide, against Legionella pneumophila were compared with those of telithromycin, clarithromycin, azithromycin, and levofloxacin. All the test agents decreased the intracellular growth of viable L. pneumophila bacteria over 96 h of incubation in both types of cells used, A/J mouse-derived macrophages and A549 human alveolar epithelial cells, at extracellular concentrations of 4× and 16× MIC, respectively. However, when the agents were removed from the medium after exposure for 2 h, regrowth of intracellular bacteria occurred in both cell systems when they were exposed to telithromycin, clarithromycin, and levofloxacin but not when they were exposed to modithromycin and azithromycin. Once-daily administration of modithromycin at a dose of 10 mg/kg of body weight for 5 days led to a significant decrease of intrapulmonary viable L. pneumophila bacteria in immunosuppressed A/J mice. The efficacy of modithromycin was superior to the efficacies of telithromycin and clarithromycin and comparable to the efficacies of azithromycin and levofloxacin. In addition, modithromycin and azithromycin inhibited the intrapulmonary regrowth of bacteria even at 72 h after the last treatment, but telithromycin and levofloxacin did not. These results suggested that modithromycin has longer-lasting cellular pharmacokinetic features like azithromycin. In conclusion, modithromycin, as well as azithromycin, has excellent in vitro and in vivo bactericidal activities and persistent efficacy against intracellular L. pneumophila. Modithromycin should be a useful agent for treatment of pulmonary infections caused by this pathogen.
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- 2011
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24. In vitro antibacterial activity of modithromycin, a novel 6,11-bridged bicyclolide, against respiratory pathogens, including macrolide-resistant Gram-positive cocci.
- Author
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Sato T, Tateda K, Kimura S, Iwata M, Ishii Y, and Yamaguchi K
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- Anti-Bacterial Agents chemistry, Gram-Negative Bacteria drug effects, Haemophilus influenzae drug effects, Ketolides chemistry, Ketolides pharmacology, Legionella drug effects, Legionella longbeachae drug effects, Legionella pneumophila drug effects, Methicillin-Resistant Staphylococcus aureus drug effects, Microbial Sensitivity Tests, Molecular Structure, Moraxella catarrhalis drug effects, Streptococcus pneumoniae drug effects, Streptococcus pyogenes drug effects, Anti-Bacterial Agents pharmacology, Bridged-Ring Compounds chemistry, Bridged-Ring Compounds pharmacology, Gram-Positive Cocci drug effects, Macrolides chemistry, Macrolides pharmacology
- Abstract
The in vitro activities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% of Streptococcus pneumoniae, Streptococcus pyogenes, and methicillin-susceptible Staphylococcus aureus (MSSA) strains, respectively. Modithromycin showed MIC(90)s of 0.125 μg/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin against ermB-carrying S. pyogenes was ≥ 32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence of mefA or mefE in both streptococci. Against Gram-negative pathogens, modithromycin showed MIC(90)s of 0.5, 8, and 0.031 μg/ml against Moraxella catarrhalis, Haemophilus influenzae, and Legionella spp., respectively. The MICs of modithromycin against M. catarrhalis and H. influenzae were higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti-Legionella activity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of the Legionella species.
- Published
- 2011
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25. Efficacy of calcium-EDTA as an inhibitor for metallo-β-lactamase in a mouse model of Pseudomonas aeruginosa pneumonia.
- Author
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Aoki N, Ishii Y, Tateda K, Saga T, Kimura S, Kikuchi Y, Kobayashi T, Tanabe Y, Tsukada H, Gejyo F, and Yamaguchi K
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- Animals, Anti-Bacterial Agents adverse effects, Calcium chemistry, Cell Line, Cell Survival drug effects, Edetic Acid adverse effects, Female, Humans, Mice, Mice, Inbred BALB C, Pseudomonas Infections microbiology, Pseudomonas aeruginosa drug effects, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents therapeutic use, Edetic Acid chemistry, Edetic Acid therapeutic use, Pneumonia drug therapy, Pneumonia microbiology, Pseudomonas Infections drug therapy, beta-Lactamase Inhibitors
- Abstract
In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-β-lactamase (MBL) and other proteases, in a mouse model of Pseudomonas aeruginosa pneumonia. The simultaneous presence of Ca-EDTA (32 μg/ml) reduced the MICs of imipenem (IPM) in all MBL-producing P. aeruginosa isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing P. aeruginosa and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (P < 0.05). Furthermore, the inhibition activity of Ca-EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC(50)) of 55 ± 8.2 μM. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in P. aeruginosa infections.
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- 2010
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26. Chromosomally encoded blaCMY-2 located on a novel SXT/R391-related integrating conjugative element in a Proteus mirabilis clinical isolate.
- Author
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Harada S, Ishii Y, Saga T, Tateda K, and Yamaguchi K
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- DNA, Bacterial genetics, Escherichia coli genetics, Klebsiella pneumoniae genetics, Molecular Sequence Data, Polymerase Chain Reaction, Salmonella typhimurium genetics, DNA Transposable Elements genetics, Proteus mirabilis genetics, beta-Lactamases genetics
- Abstract
Integrating conjugative elements (ICEs) are mobile genetic elements that can transfer from the chromosome of a host to the chromosome of a new host through the process of excision, conjugation, and integration. Although SXT/R391-related ICEs, originally demonstrated in Vibrio cholerae O139 isolates, have become prevalent among V. cholerae isolates in Asia, the prevalence of the ICEs among gram-negative bacteria other than Vibrio spp. remains unknown. In addition, SXT/R391-related ICEs carrying genes conferring resistance to extended-spectrum cephalosporins have never been described. Here we carried out a genetic analysis of a cefoxitin-resistant Proteus mirabilis clinical isolate, TUM4660, which revealed the presence of a novel SXT/R391-related ICE, ICEPmiJpn1. ICEPmiJpn1 had a core genetic structure showing high similarity to that of R391 and carried xis and int genes completely identical to those of R391, while an IS10-mediated composite transposon carrying bla(CMY-2) was integrated into the ICE. A nucleotide sequence identical to the 3' part of ISEcp1 was located upstream of the bla(CMY-2) gene, and other genes observed around bla(CMY-2) in earlier studies were also present. Furthermore, the nucleotide sequences of hot spot 2 and hot spot 4 in ICEPmiJpn1 showed high similarity to that of hot spot 2 in SXT(MO10) and with a part of the nucleotide sequence found in P. mirabilis ATCC 29906, respectively. ICEPmiJpn1 was successfully transferred to Escherichia coli, Klebsiella pneumoniae, Salmonella enterica serovar Typhimurium, and Citrobacter koseri in conjugation experiments. These observations suggest that ICEs may contribute to the dissemination of antimicrobial resistance genes among clinically relevant Enterobacteriaceae, which warrants careful observation of the prevalence of ICEs, including SXT/R391-related ICEs.
- Published
- 2010
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27. In vitro potentiation of carbapenems with ME1071, a novel metallo-beta-lactamase inhibitor, against metallo-beta-lactamase- producing Pseudomonas aeruginosa clinical isolates.
- Author
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Ishii Y, Eto M, Mano Y, Tateda K, and Yamaguchi K
- Subjects
- Enzyme Inhibitors chemistry, Microbial Sensitivity Tests, Molecular Structure, Carbapenems pharmacology, Enzyme Inhibitors pharmacology, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa enzymology, beta-Lactamase Inhibitors, beta-Lactamases metabolism
- Abstract
ME1071, a maleic acid derivative, is a novel specific inhibitor for metallo-beta-lactamases (MBL). In this study, the potentiation of ME1071 in combination with several beta-lactams was evaluated using MBL-producing Pseudomonas aeruginosa isolates. The rates of susceptibility of MBL producers to carbapenems (imipenem, biapenem, and doripenem) and ceftazidime were increased by 8 to 27% in the presence of 32 microg/ml of ME1071. The corresponding resistance rates were decreased by 13 to 46%, respectively. On the other hand, ME1071 showed weaker or no potentiation with non-MBL producers. The K(i) value of ME1071 for IMP-1 was 0.4 microM, significantly lower than the K(m) values of carbapenems for the IMP-1 enzyme. On the other hand, the K(i) value of ME1071 for VIM-2 was 120 microM, higher than the K(m) values of carbapenems for the VIM-2 enzyme. Results of this study indicate that ME1071 can potentiate the activity of ceftazidime and carbapenems against MBL-producing strains of P. aeruginosa.
- Published
- 2010
- Full Text
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28. Anti-Clostridium difficile potential of tetramic acid derivatives from Pseudomonas aeruginosa quorum-sensing autoinducers.
- Author
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Ueda C, Tateda K, Horikawa M, Kimura S, Ishii Y, Nomura K, Yamada K, Suematsu T, Inoue Y, Ishiguro M, Miyairi S, and Yamaguchi K
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Clostridioides difficile ultrastructure, Homoserine chemistry, Magnetic Resonance Spectroscopy, Microbial Sensitivity Tests, Microscopy, Electron, Transmission, Pyrrolidinones chemical synthesis, Pyrrolidinones chemistry, Quorum Sensing physiology, Anti-Bacterial Agents pharmacology, Clostridioides difficile drug effects, Homoserine analogs & derivatives, Lactones chemistry, Pyrrolidinones pharmacology
- Abstract
We have examined the potential bactericidal activities of several tetramic acids derived from Pseudomonas autoinducers against Clostridium difficile, a cause of antibiotic-associated pseudomembranous colitis. Clinical isolates of C. difficile (n=4) were incubated in broth with a chemically synthesized Pseudomonas autoinducer and its tetramic acid derivatives. The structure-activity relationship and the mechanisms of action were examined by a time-killing assay and by determination of the morphological/staining characteristics. The use of some tetramic acids derived from N-3-oxododecanoyl L-homoserine lactone resulted in more than 3-log reductions in the viability of C. difficile within 30 min at 30 microM. The outer membrane was suggested to be one of the targets for the bactericidal activity of tetramic acid, because disturbance of the bacterial outer surface was demonstrated by alteration of the Gram-staining characteristic and electron microscopy. The data for the tetramic acid derivatives demonstrate that the keto-enol structure and the length of the acyl side chain of tetramic acid may be essential for the antibacterial activity of this molecule. These results suggest the potential for tetramic acid derivatives to be novel agents with activity against C. difficile.
- Published
- 2010
- Full Text
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29. Antimicrobial activities of piperacillin-tazobactam against Haemophilus influenzae isolates, including beta-lactamase-negative ampicillin-resistant and beta-lactamase-positive amoxicillin-clavulanate-resistant isolates, and mutations in their quinolone resistance-determining regions.
- Author
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Hirakata Y, Ohmori K, Mikuriya M, Saika T, Matsuzaki K, Hasegawa M, Hatta M, Yamamoto N, Kunishima H, Yano H, Kitagawa M, Arai K, Kawakami K, Kobayashi I, Jones RN, Kohno S, Yamaguchi K, and Kaku M
- Subjects
- Amoxicillin-Potassium Clavulanate Combination, Ciprofloxacin pharmacology, Drug Resistance, Multiple, Bacterial genetics, Haemophilus influenzae genetics, Microbial Sensitivity Tests, Mutation, Ampicillin pharmacology, Anti-Bacterial Agents pharmacology, Haemophilus influenzae drug effects, beta-Lactamases pharmacology
- Abstract
Beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (< or = 1 microg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. influenzae should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant H. influenzae isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to beta-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent H. influenzae clinical isolates, including 100 beta-lactamase-negative ampicillin-susceptible, beta-lactamase-positive ampicillin-resistant, BLNAR, and beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the ftsI gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among beta-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of H. influenzae, with all MICs at < or = 0.5 microg/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of > or = 21 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the ftsI gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 microg/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 microg/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent beta-lactam tested against all classes of H. influenzae isolates. It is possible that fluoroquinolone-resistant H. influenzae will emerge since several clinical isolates carried mutations in their QRDRs.
- Published
- 2009
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30. Limited inhibitory effects of oseltamivir and zanamivir on human sialidases.
- Author
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Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, and Miyagi T
- Subjects
- Cell Line, Humans, In Vitro Techniques, Kinetics, Neuraminidase genetics, Orthomyxoviridae enzymology, RNA, Messenger genetics, RNA, Messenger metabolism, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins genetics, Antiviral Agents adverse effects, Enzyme Inhibitors adverse effects, Neuraminidase antagonists & inhibitors, Oseltamivir adverse effects, Zanamivir adverse effects
- Abstract
Oseltamivir (Tamiflu) and zanamivir (Relenza), two extensively used clinically effective anti-influenza drugs, are viral sialidase (also known as neuraminidase) inhibitors that prevent the release of progeny virions and thereby limit the spread of infection. Recently mortalities and neuropsychiatric events have been reported with the use of oseltamivir, especially in pediatric cases in Japan, suggesting that these drugs might also inhibit endogenous enzymes involved in sialic acid metabolism, including sialidase, sialyltransferase, and CMP-synthase, in addition to their inhibitory effects on the viral sialidase. The possible inhibition could account for some of the rare side effects of oseltamivir. However, there has been little direct evidence in regard to the sensitivities of animal sialidases to these drugs. Here, we examined whether these inhibitors might indeed affect the activities of human sialidases, which differ in primary structures and enzyme properties but possess tertiary structures similar to those of the viral enzymes. Using recombinant enzymes corresponding to the four human sialidases identified so far, we found that oseltamivir carboxylate scarcely affected the activities of any of the sialidases, even at 1 mM, while zanamivir significantly inhibited the human sialidases NEU3 and NEU2 in the micromolar range (K(i), 3.7 +/- 0.48 and 12.9 +/- 0.07 microM, respectively), providing a contrast to the low nanomolar concentrations at which these drugs block the activity of the viral sialidases.
- Published
- 2008
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31. Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice.
- Author
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Watanabe R, Matsumoto T, Sano G, Ishii Y, Tateda K, Sumiyama Y, Uchiyama J, Sakurai S, Matsuzaki S, Imai S, and Yamaguchi K
- Subjects
- Administration, Oral, Animals, Cytokines blood, Disease Models, Animal, Humans, Liver metabolism, Lower Gastrointestinal Tract microbiology, Mice, Mice, Inbred ICR, Sepsis blood, Sepsis microbiology, Sepsis mortality, Biological Therapy, Pseudomonas Infections therapy, Pseudomonas Phages, Pseudomonas aeruginosa, Sepsis therapy
- Abstract
We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P<0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-alpha, interleukin-1beta [IL-1beta], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.
- Published
- 2007
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32. Kinetics study of KPC-3, a plasmid-encoded class A carbapenem-hydrolyzing beta-lactamase.
- Author
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Alba J, Ishii Y, Thomson K, Moland ES, and Yamaguchi K
- Subjects
- Amino Acid Sequence, Hydrolysis, Kinetics, beta-Lactamases chemistry, Carbapenems metabolism, Escherichia coli enzymology, beta-Lactamases metabolism
- Abstract
The kinetic activity of KPC-3, a plasmid-encoded class A carbapenemase, was studied. It hydrolyzed penicillins, cephalosporins, carbapenems, and even sulbactam. The best substrate was cephalothin (k(cat/K)m = 3.48 microM(-1) s(-1)). The efficiency of the enzyme was similar for imipenem and meropenem (k(cat)/K(m), 1.4 and 1.94 microM(-1) s(-1), respectively).
- Published
- 2005
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33. Extended-spectrum-beta-lactamase-producing Escherichia coli strains isolated from farm animals from 1999 to 2002: report from the Japanese Veterinary Antimicrobial Resistance Monitoring Program.
- Author
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Kojima A, Ishii Y, Ishihara K, Esaki H, Asai T, Oda C, Tamura Y, Takahashi T, and Yamaguchi K
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Cephalosporin Resistance genetics, Cephalosporins pharmacology, Escherichia coli enzymology, Escherichia coli genetics, Feces microbiology, Japan, Microbial Sensitivity Tests veterinary, beta-Lactamases genetics, Animals, Domestic microbiology, Chickens microbiology, Escherichia coli drug effects, beta-Lactamases biosynthesis
- Abstract
A nationwide surveillance for antimicrobial susceptibility in Escherichia coli strains isolated from food-producing animals in Japan was conducted from 1999 to 2002. Eighteen cefazolin-resistant E. coli strains were isolated from broilers. Six were CTX-M-type producing, and eight were CMY-2 producing, while eight had mutations at the ampC promoter region.
- Published
- 2005
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34. Novel SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers resistance to ceftazidime but not cefazolin.
- Author
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Ma L, Alba J, Chang FY, Ishiguro M, Yamaguchi K, Siu LK, and Ishii Y
- Subjects
- Cloning, Molecular, Conjugation, Genetic, DNA, Bacterial genetics, Deoxyribonucleases, Type II Site-Specific genetics, Drug Resistance, Bacterial, Escherichia coli Infections microbiology, Humans, Infant, Isoelectric Focusing, Kinetics, Male, Microbial Sensitivity Tests, Models, Molecular, Molecular Sequence Data, Open Reading Frames genetics, Plasmids genetics, Taiwan, Cefazolin pharmacology, Ceftazidime pharmacology, Cephalosporins pharmacology, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli Proteins metabolism, beta-Lactamases metabolism
- Abstract
A new SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers high-level resistance to ceftazidime but not cefotaxime or cefazolin was identified from a national surveillance study conducted in Taiwan in 1998. An Escherichia coli isolate resistant to ampicillin, cephalothin, and ceftazidime but sensitive to cefoxitin, ceftriaxone, cefotaxime, imipenem, and a narrow-spectrum cephem (cefazolin) was isolated from the urine of a patient treated with beta-lactam antibiotics. Resistance to beta-lactams was conjugatively transferred with a plasmid of about 50 kbp. The pI of this enzyme was 8.3. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 861 bases (GenBank accession number AY223863). Kinetic parameters showed that SHV-57 had a poor affinity to cefazolin. The K(m) value toward cefazolin (5.57 x 10(3) muM) was extremely high in comparison to those toward ceftazidime (30.9 muM) and penicillin G (67 muM), indicating its low affinity to cefazolin. Although the K(m) value of the beta-lactamase inhibitor was too high for the study of catalytic activity (k(cat)), indicating the low k(cat) of SHV-57, the SHV-57 carrier was highly susceptible to a beta-lactam-beta-lactamase inhibitor combination. Comparison of the three-dimensional molecular model of SHV-57 with that of the SHV-1 beta-lactamase suggests that the substitution of arginine for leucine-169 in the Omega loop is important for the substrate specificity.
- Published
- 2005
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35. Role of a mutation at position 167 of CTX-M-19 in ceftazidime hydrolysis.
- Author
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Kimura S, Ishiguro M, Ishii Y, Alba J, and Yamaguchi K
- Subjects
- Aztreonam pharmacology, Escherichia coli enzymology, Escherichia coli genetics, Hydrolysis, Kinetics, Microbial Sensitivity Tests, Models, Molecular, Monobactams pharmacology, Mutagenesis, Site-Directed, Ceftazidime metabolism, Cephalosporins metabolism, Mutation physiology, beta-Lactamases genetics, beta-Lactamases metabolism
- Abstract
CTX-M-19 is a recently identified ceftazidime-hydrolyzing extended-spectrum beta-lactamase, which differs from the majority of CTX-M-type beta-lactamases that preferentially hydrolyze cefotaxime but not ceftazidime. To elucidate the mechanism of ceftazidime hydrolysis by CTX-M-19, the beta-lactam MICs of a CTX-M-19 producer, and the kinetic parameters of the enzyme were confirmed. We reconfirmed here that CTX-M-19 is also stable at a high enzyme concentration in the presence of bovine serum albumin (20 micro g/ml). Under this condition, we obtained more accurate kinetic parameters and determined that cefotaxime (k(cat)/K(m), 1.47 x 10(6) s(-1) M(-1)), cefoxitin (k(cat)/K(m), 62.2 s(-1) M(-1)), and aztreonam (k(cat)/K(m), 1.34 x 10(3) s(-1) M(-1)) are good substrates and that imipenem (k(+2)/K, 1.20 x 10(2) s(-1) M(-1)) is a poor substrate. However, CTX-M-18 and CTX-M-19 exhibited too high a K(m) value (2.7 to 5.6 mM) against ceftazidime to obtain their catalytic activity (k(cat)). Comparison of the MICs with the catalytic efficiency (k(cat)/K(m)) of these enzymes showed that some beta-lactams, including cefotaxime, ceftazidime, and aztreonam showed a similar correlation. Using the previously reported crystal structure of the Toho-1 beta-lactamase, which belongs to the CTX-M-type beta-lactamase group, we have suggested characteristic interactions between the enzymes and the beta-lactams ceftazidime, cefotaxime, and aztreonam by molecular modeling. Aminothiazole-bearing beta-lactams require a displacement of the aminothiazole moiety due to a severe steric interaction with the hydroxyl group of Ser167 in CTX-M-19, and the displacement affects the interaction between Ser130 and the acidic group such as carboxylate and sulfonate of beta-lactams.
- Published
- 2004
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36. Pharmacodynamics of S-3578, a novel cephem, in murine lung and systemic infection models.
- Author
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Miyazaki S, Okazaki K, Tsuji M, and Yamaguchi K
- Subjects
- Animals, Area Under Curve, Cefepime, Cephalosporins pharmacology, Colony Count, Microbial, Female, Injections, Subcutaneous, Methicillin Resistance, Mice, Mice, Inbred CBA, Mice, Inbred ICR, Microbial Sensitivity Tests, Pneumonia, Pneumococcal metabolism, Pneumonia, Pneumococcal microbiology, Sepsis drug therapy, Sepsis metabolism, Sepsis microbiology, Staphylococcal Infections metabolism, Staphylococcal Infections microbiology, Staphylococcus aureus drug effects, Survival Analysis, Tissue Distribution, Cephalosporins pharmacokinetics, Cephalosporins therapeutic use, Lung metabolism, Pneumonia, Pneumococcal drug therapy, Staphylococcal Infections drug therapy
- Abstract
S-3578 is a novel beta-lactam with enhanced activity against drug-resistant gram-positive cocci such as methicillin-resistant Staphylococcus aureus (MRSA). We used murine penicillin-resistant Streptococcus pneumoniae lung infection and neutropenic murine systemic MRSA infection models to determine the pharmacokinetic (PK)-pharmacodynamic (PD) parameter that best correlated with efficacy. Pharmacokinetic studies revealed that the maximum concentration in serum/dose values for S-3578 and cefepime in plasma in the lung infection model were 1.21 to 1.54 and 0.97 to 1.29, respectively; those for S-3578 in plasma in the systemic infection model were 0.78 to 1.02. The area under the concentration-time curve (AUC)/dose values for S-3578 and cefepime in plasma in the lung infection model were 0.98 to 1.13 and 0.77 to 1.04, respectively, and those for S-3578 in plasma in the systemic infection model were 1.03 to 1.11. The half-lives of S-3578 and cefepime in plasma in the lung infection model were 0.29 to 0.38 and 0.29 to 0.34, respectively, and those of S-3578 in plasma in the systemic infection model were 0.40 to 0.61. The time above the MIC was the PK-PD parameter that best correlated with efficacy in the murine lung infection model (R(2) = 84 and 92% for S-3578 and cefepime in plasma, respectively). There was a twofold increase in the dose of S-3578 in the systemic infection model compared to that in the pneumonia model, yet the AUCs were the same. This may be due to the different MICs for the two pathogens.
- Published
- 2004
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37. CTX-M-14, a plasmid-mediated CTX-M type extended-spectrum beta-lactamase isolated from Escherichia coli.
- Author
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Ma L, Ishii Y, Chang FY, Yamaguchi K, Ho M, and Siu LK
- Subjects
- Amino Acid Substitution, Aztreonam pharmacology, Cefotaxime pharmacology, Ceftazidime pharmacology, Cephalosporin Resistance, Cephalosporins pharmacology, Escherichia coli drug effects, Isoelectric Focusing, Kinetics, Microbial Sensitivity Tests, Monobactams pharmacology, RNA, Bacterial genetics, Reverse Transcriptase Polymerase Chain Reaction, Taiwan epidemiology, Escherichia coli enzymology, Escherichia coli genetics, Plasmids genetics, beta-Lactamases genetics, beta-Lactamases metabolism
- Abstract
Four Escherichia coli isolates harboring CTX-M-14, with a single Ala231-->Val substitution compared to CTX-M-9, had three different ribotypes. Cefotaxime resistance was plasmid encoded and conjugatively transferable. Three isolates had the same plasmid restriction enzyme digestion profile, suggesting clonal spread of a resistant plasmid. A high k(cat)/K(m) value for cefotaxime (20.3 microM(-1) s(-1)) but low values for ceftazidime and aztreonam (< 0.02 microM(-1) s(-1)) were observed in hydrolysis assays, indicating resistance to cefotaxime (MIC > or = 64 microg/ml) but susceptibility to ceftazidime (MIC < or = 2 microg/ml).
- Published
- 2002
- Full Text
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38. In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae.
- Author
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Okamoto H, Miyazaki S, Tateda K, Ishii Y, and Yamaguchi K
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Drug Resistance, Erythromycin pharmacology, Haemophilus Infections microbiology, Half-Life, Male, Mice, Mice, Inbred CBA, Mice, Inbred ICR, Microbial Sensitivity Tests, Pneumococcal Infections microbiology, Respiratory Tract Infections drug therapy, Respiratory Tract Infections microbiology, Anti-Bacterial Agents therapeutic use, Haemophilus Infections drug therapy, Haemophilus influenzae, Ketolides, Macrolides, Pneumococcal Infections drug therapy, Streptococcus pneumoniae
- Abstract
The in vivo activity of telithromycin against erythromycin A- and penicillin G-resistant Streptococcus pneumoniae was superior to that of azithromycin, clarithromycin, cefdinir, and levofloxacin. In respiratory tract infections caused by erythromycin A-susceptible S. pneumoniae or Haemophilus influenzae in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin.
- Published
- 2001
- Full Text
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39. Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa.
- Author
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Tateda K, Comte R, Pechere JC, Köhler T, Yamaguchi K, and Van Delden C
- Subjects
- DNA-Binding Proteins drug effects, Lac Operon drug effects, Trans-Activators drug effects, Anti-Bacterial Agents pharmacology, Azithromycin pharmacology, Bacterial Proteins drug effects, Membrane Transport Proteins, Pseudomonas aeruginosa drug effects
- Abstract
We report that 2 microg of azithromycin/ml inhibits the quorum-sensing circuitry of Pseudomonas aeruginosa strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding genes lasR and rhlR but not that of the autoinducer synthase-encoding gene lasI. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.
- Published
- 2001
- Full Text
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40. In vitro and in vivo antibacterial activities of L-084, a novel oral carbapenem, against causative organisms of respiratory tract infections.
- Author
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Miyazaki S, Hosoyama T, Furuya N, Ishii Y, Matsumoto T, Ohno A, Tateda K, and Yamaguchi K
- Subjects
- Animals, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents pharmacology, Area Under Curve, Carbapenems pharmacokinetics, Carbapenems therapeutic use, Haemophilus Infections drug therapy, Haemophilus Infections microbiology, Haemophilus influenzae drug effects, Male, Mice, Mice, Inbred CBA, Mice, Inbred ICR, Microbial Sensitivity Tests, Prodrugs pharmacokinetics, Prodrugs pharmacology, Prodrugs therapeutic use, Respiratory Tract Infections drug therapy, Streptococcal Infections drug therapy, Streptococcal Infections microbiology, Streptococcus pneumoniae drug effects, Carbapenems pharmacology, Respiratory Tract Infections microbiology
- Abstract
L-084 (a prodrug of LJC 11,036 [L-036]) is a new oral carbapenem. Here we compared the in vitro and in vivo antibacterial activities of L-036 with those of imipenem, faropenem, ceditoren-pivoxil, cefdinir, amoxicillin, and levofloxacin. The MICs at which 90% of the isolates were inhibited of L-036 against methicillin-susceptible staphylococci, Streptococcus pneumoniae including penicillin-resistant organisms, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae including ampicillin-resistant organisms, Legionella pneumophila, and Moraxella catarrhalis were equal to or less than 1 microg/ml. In pharmacokinetics studies of L-084 in lungs of mice, the maximum concentration in serum, half-life, and area under the concentration-time curve of this drug were 9.09 microg/g of tissue, 6.18 h, and 31.0 microg. h/ml, respectively. In murine respiratory infection models of penicillin-susceptible and -resistant S. pneumoniae and H. influenzae, the efficacies of L-084 were better than those of reference drugs. Our results indicate that the in vitro high potency and good distribution in the lungs might be the underlying mechanisms of its efficacy in the murine model of pneumonia.
- Published
- 2001
- Full Text
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41. Fosfomycin alters lipopolysaccharide-induced inflammatory cytokine production in mice.
- Author
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Matsumoto T, Tateda K, Miyazaki S, Furuya N, Ohno A, Ishii Y, Hirakata Y, and Yamaguchi K
- Subjects
- Animals, Cytokines blood, Dose-Response Relationship, Drug, Inflammation chemically induced, Interleukin-1 biosynthesis, Interleukin-1 blood, Male, Mice, Time Factors, Tumor Necrosis Factor-alpha biosynthesis, Anti-Bacterial Agents pharmacology, Cytokines biosynthesis, Endotoxins toxicity, Escherichia coli, Fosfomycin pharmacology, Inflammation metabolism, Lipopolysaccharides toxicity
- Abstract
To determine the mechanisms of immunomodulating action of fosfomycin (FOF), we examined its effect on the production of inflammatory cytokines in mice injected with lipopolysaccharide (LPS). Treatment with FOF significantly lowered the peak serum levels of tumor necrosis factor alpha and interleukin-1 beta, indicating that FOF alters inflammatory cytokine production after LPS stimulation.
- Published
- 1999
- Full Text
- View/download PDF
42. Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.
- Author
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Matsumoto T, Tateda K, Miyazaki S, Furuya N, Ohno A, Ishii Y, Hirakata Y, and Yamaguchi K
- Subjects
- Animals, Cyclophosphamide pharmacology, Cytokines blood, Granulocyte-Macrophage Colony-Stimulating Factor blood, Interleukin-10 blood, Intestinal Diseases immunology, Male, Mice, Pseudomonas Infections immunology, Recombinant Proteins therapeutic use, Sepsis immunology, Interleukin-10 therapeutic use, Intestinal Diseases drug therapy, Pseudomonas Infections drug therapy, Sepsis drug therapy
- Abstract
We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
- Published
- 1998
- Full Text
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43. In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic.
- Author
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Tamura S, Miyazaki S, Tateda K, Ohno A, Ishii Y, Matsumoto T, Furuya N, and Yamaguchi K
- Subjects
- Animals, Bacteremia drug therapy, Disease Models, Animal, Escherichia coli drug effects, Male, Mice, Mice, Inbred CBA, Mice, Inbred ICR, Microbial Sensitivity Tests, Pneumonia, Pneumococcal drug therapy, Staphylococcus drug effects, Streptococcus drug effects, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Lactams, Prodrugs pharmacology
- Abstract
The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.
- Published
- 1998
- Full Text
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44. Cloning and sequencing of the gene encoding Toho-2, a class A beta-lactamase preferentially inhibited by tazobactam.
- Author
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Ma L, Ishii Y, Ishiguro M, Matsuzawa H, and Yamaguchi K
- Subjects
- Amino Acid Sequence, Base Sequence, Escherichia coli enzymology, Molecular Sequence Data, Penicillanic Acid analogs & derivatives, Penicillanic Acid pharmacology, Protein Conformation, Sequence Alignment, Sequence Homology, Amino Acid, Tazobactam, beta-Lactamases drug effects, Bacterial Proteins genetics, Enzyme Inhibitors pharmacology, Escherichia coli genetics, Escherichia coli Proteins, beta-Lactamase Inhibitors, beta-Lactamases genetics
- Abstract
Escherichia coli TUM1083, which is resistant to ampicillin, carbenicillin, cephaloridine, cephalothin, piperacillin, cefuzonam, and aztreonam while being sensitive to cefoxitin, moxalactam, cefmetazole, ceftazidime, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-2) purified from the bacteria hydrolyzed beta-lactam antibiotics such as penicillin G, carbenicillin, cephaloridine, cefoxitin, cefotaxime, ceftazidime, and aztreonam and especially had increased relative hydrolysis rates for cephalothin, cephaloridine, cefotaxime, and ceftizoxime. Different from other extended-spectrum beta-lactamases, Toho-2 was inhibited 16-fold better by the beta-lactamase inhibitor tazobactam than by clavulanic acid. Resistance to beta-lactams was transferred by conjugation from E. coli TUM1083 to E. coli ML4909, and the transferred plasmid was about 54.4 kbp, belonging to the incompatibility group IncFII. The cefotaxime resistance gene for Toho-2 was subcloned from the 54.4-kbp plasmid. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 981 bases. The nucleotide sequence of the gene (DDBJ accession no. D89862) designated as bla(toho) was found to have 76.3% identity to class A beta-lactamase CTX-M-2 and 76.2% identity to Toho-1. It has 55.9% identity to SHV-1 beta-lactamase and 47.5% identity to TEM-1 beta-lactamase. Therefore, the newly isolated beta-lactamase designated as Toho-2 produced by E. coli TUM1083 is categorized as an enzyme similar to Toho-1 group beta-lactamases rather than to mutants of TEM or SHV enzymes. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 327 amino acid residues. Comparison of Toho-2 with other beta-lactamase (non-Toho-1 group) suggests that the substitutions of threonine for Arg-244 and arginine for Asn-276 are important for the extension of the substrate specificity.
- Published
- 1998
- Full Text
- View/download PDF
45. In vivo activity of HSR-903, a new fluoroquinolone, against respiratory pathogens.
- Author
-
Yoshizumi S, Domon H, Miyazaki S, and Yamaguchi K
- Subjects
- Animals, Anti-Infective Agents pharmacokinetics, Area Under Curve, Haemophilus Infections microbiology, Levofloxacin, Mice, Mice, Inbred ICR, Microbial Sensitivity Tests, Ofloxacin pharmacokinetics, Ofloxacin therapeutic use, Quinolones pharmacokinetics, Respiratory Tract Infections microbiology, Streptococcal Infections microbiology, Anti-Infective Agents therapeutic use, Fluoroquinolones, Haemophilus Infections drug therapy, Haemophilus influenzae, Quinolones therapeutic use, Respiratory Tract Infections drug therapy, Streptococcal Infections drug therapy, Streptococcus pneumoniae
- Abstract
The in vivo activity of HSR-903, a new fluoroquinolone, against major bacteria which cause respiratory tract infections was evaluated. HSR-903 was active against experimental respiratory tract infections in mice challenged with penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and Haemophilus influenzae strains. Treatment with HSR-903 reduced the bacterial numbers in infected murine lungs. In accord with the pulmonary clearance results, the rates of survival for mice treated with HSR-903, sparfloxacin, levofloxacin, ciprofloxacin, and benzylpenicillin were 50, 30, 10, 0, and 0%, respectively, 14 days after being infected with penicillin-resistant S. pneumoniae. A pharmacokinetic study with pneumonic mice showed that the levels of HSR-903 in the lungs were seven to eight times higher than those in the plasma. These results indicate that clinical studies of HSR-903 against respiratory tract infections may be warranted.
- Published
- 1998
- Full Text
- View/download PDF
46. In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.
- Author
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Yamaguchi K, Domon H, Miyazaki S, Tateda K, Ohno A, Ishii K, Matsumoto T, and Furuya N
- Subjects
- Animals, Carbapenems blood, Carbapenems therapeutic use, Cilastatin pharmacology, Drug Resistance, Microbial, Gram-Negative Bacterial Infections blood, Gram-Negative Bacterial Infections drug therapy, Gram-Positive Bacterial Infections blood, Gram-Positive Bacterial Infections drug therapy, Humans, Male, Mice, Mice, Inbred ICR, Microbial Sensitivity Tests, Prodrugs therapeutic use, Protease Inhibitors pharmacology, Sepsis blood, Sepsis drug therapy, Carbapenems pharmacology, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Prodrugs pharmacology
- Abstract
CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.
- Published
- 1998
- Full Text
- View/download PDF
47. In vitro and in vivo antibacterial activities of S-4661, a new carbapenem.
- Author
-
Tsuji M, Ishii Y, Ohno A, Miyazaki S, and Yamaguchi K
- Subjects
- Animals, Anti-Bacterial Agents blood, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents therapeutic use, Carbapenems blood, Carbapenems chemistry, Carbapenems pharmacology, Carbapenems therapeutic use, Disease Models, Animal, Doripenem, Male, Mice, Microbial Sensitivity Tests, Penicillin Resistance, Pneumococcal Infections blood, Anti-Bacterial Agents pharmacology, Enterobacteriaceae drug effects, Haemophilus influenzae drug effects, Moraxella drug effects, Pneumococcal Infections drug therapy
- Abstract
The in vitro and in vivo antibacterial activities of S-4661, a new 1beta-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 microg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 microg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.
- Published
- 1998
- Full Text
- View/download PDF
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