Issei Tokimatsu

Oita University, Ōita, Ōita, Japan

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Publications (75)90.73 Total impact

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    ABSTRACT: The guideline for the "Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)," published by the Japanese Society of Chemotherapy in January 2012, was proposed to achieve consistency with FDA guidelines based on the concept of clinical evaluation used in Japan. We assessed the clinical efficacy of levofloxacin (LVFX) in patients with bacterial pneumonia according to this new set of guidelines for the first time. The clinical efficacy of LVFX in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) at the test of cure (TOC) was 87.5% (56/64) and 85.7% (6/7), respectively, with an overall efficacy of 87.3% (62/71). The clinical efficacy of LVFX at TOC was as follows: intravenous 81.5% (22/27), oral 88.9% (24/27), switchover from intravenous to oral administration 100% (10/10), respectively. The bacterial eradication rate in the patients with CAP and HCAP and overall efficacy at the end of therapy (EOT) was 95.3% (41/43), 100.0% (4/4) and 95.7% (45/47), respectively. The frequent causative bacterial strains included Streptococcus pneumoniae (18), Haemophilus influenzae (14) and Moraxella catarrhalis (6). The incidence of adverse reactions in the patients whose safety was evaluated was 15.7% (14/89), similar to that previously reported. The clinical efficacy of LVFX at the early phase, EOT and TOC of CAP, as assessed according to the new and former guidelines, was 70.4% (38/54) and 27.8% (15/54), 87.0% (60/69) and 79.1% (53/67), 87.5% (56/64) and 88.1% (59/67), respectively, with no significant differences. Therefore, the new efficacy evaluation method can be used in exchange for the former evaluation method.
    Journal of Infection and Chemotherapy 04/2014; · 1.55 Impact Factor
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    ABSTRACT: Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course.
    Journal of Infection and Chemotherapy 04/2014; · 1.55 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). NHLF were pretreated with 100 nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-β1 (TGF-β1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. TGF-β1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C-X-C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. Pitavastatin appeared to inhibit TGF-β1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin.
    Life sciences 11/2013; · 2.56 Impact Factor
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    ABSTRACT: BACKGROUND: Therapeutic drug monitoring (TDM) of voriconazole is important to optimize efficacy and to minimize toxicity and intolerance. In this study, we evaluated the effect of sustained high plasma trough concentration of voriconazole on the incidence of hepatotoxicity in hospitalized Japanese patients. METHODS: Thirty-nine patients were divided into 3 groups according to trough concentrations in two consecutive TDMs: <4μg/ml in the first TDM (group A, n=25), > 4μg/ml in the first and <4μg/ml in the second TDM (group B, n=8), >4μg/ml in both first and second TDMs (group C, n=6). RESULTS: Incidence of hepatotoxicity in groups A, B and C was 16.0, 25.0 and 83.3%, and significant differences were observed between groups A and C and groups B and C. Multiple logistic regression analysis identified the classification into groups A, B and C as an independent variable of hepatotoxicity. CONCLUSIONS: These results suggest that sustained high trough concentration of voriconazole may increase the risk of hepatotoxicity, and decreasing trough concentration to <4μg/ml by dose adjustment after the initial TDM may reduce the incidence of hepatotoxicity in patients treated with voriconazole.
    Clinica chimica acta; international journal of clinical chemistry 06/2013; · 2.54 Impact Factor
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    Blood research. 06/2013; 48(2):154-6.
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    ABSTRACT: The switch from intravenous to oral antibiotic therapy is recommended for treating hospitalized patients with community-acquired pneumonia (CAP). We performed a multicenter, randomized study to assess the benefit of switching from intravenous sulbactam/ampicillin (SBT/ABPC) to oral garenoxacin (GRNX) in patients with CAP. Among adult CAP patients who must be hospitalized for intravenous antibiotic treatment, those with Pneumonia Patient Outcomes Research Team (PORT) scores of II-IV (mild to moderate) were initially treated with intravenous SBT/ABPC (6 g/day) for 3 days. A total of 108 patients who fulfilled the inclusion criteria (improved respiratory symptoms, CRP < 15 mg/dl, adequately improved oral intake, fever ≤ 38 °C for ≥ 12 h), were divided into two groups based on the antibiotic administered, the GRNX (switch to GRNX 400 mg/day) and SBT/ABPC groups (continuous administration of SBT/ABPC), for 4 days. Improvement in clinical symptoms, chest radiographic findings, and clinical effectiveness were evaluated by a central review board. Improvement in clinical symptoms was 96.3 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Improvement in chest radiographic findings was 94.4 and 90.2 % and clinical effectiveness was 94.4 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Microbiological efficacy was 90.9 and 69.2 % in the GRNX and SBT/ABPC groups, respectively. There were no significant differences between the groups. Converting to GRNX was as effective as continuous SBT/ABPC treatment in mild to moderate CAP patients in whom initial intravenous antibiotic treatment was successful.
    Journal of Infection and Chemotherapy 05/2013; · 1.55 Impact Factor
  • Journal of Infection and Chemotherapy 05/2013; · 1.55 Impact Factor
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    Journal of Infection and Chemotherapy 05/2013; · 1.55 Impact Factor
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    ABSTRACT: Background: We analyzed the pharmacokinetic-pharmacodynamic relationship of vancomycin to determine the drug exposure parameters that correlate with the efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus pneumonia and evaluated the need to use peak concentration in therapeutic drug monitoring (TDM). Methods: Serum drug concentrations of 31 hospitalized patients treated with vancomycin for methicillin-resistant S. aureus pneumonia were collected. Results: Significant differences in trough concentration (C(min))/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC(0-24))/MIC were observed between the response and non-response groups. Significant differences in C(min) and AUC(0-24) were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of C(min)/MIC and AUC(0-24)/MIC for efficacy and of C(min) and AUC(0-24) for safety of vancomycin. Conclusions: These results suggest little need to use peak concentration in vancomycin TDM because C(min)/MIC and C(min) are sufficient to predict the efficacy and safety of vancomycin.
    Chemotherapy 11/2012; 58(4):308-312. · 2.07 Impact Factor
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    ABSTRACT: Aspergillus causes several pulmonary complications, but bronchial stump aspergillosis (BSA) is very rare. To date, 31 cases of bronchial stump aspergillosis have been reported in the English, German, and Japanese literature. The bronchial stump was closed by hand-sewn suturing in most cases, but we report herein two cases of BSA that developed after stapled closure of the bronchial stump.
    The Annals of thoracic surgery 10/2012; 94(4):1324–1326. · 3.45 Impact Factor
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    ABSTRACT: Aim:  Deaths from aspiration pneumonia in elderly patients are occasionally considered to be "death from age-related physical debility", because most aspiration pneumonias are a result of aging and lead to death without any definitive therapy. The aim of the present study was to assess physicians' attitudes toward the diagnosis of and actual description of "death from age-related physical debility" on death certificates for deceased patients with aspiration pneumonia. Methods:  This study surveyed 62 Japanese physicians including 36 pulmonologists and 26 other physicians who treat patients with pneumonia. Their attitudes regarding consideration and actually recorded "death from age-related physical debility" for deceased patients with aspiration pneumonia were assessed by using anonymous questionnaires, which included the decision-making process and the necessity of detailed diagnostic criteria. Results:  A total of 32 (52%) respondents had considered deceased patients with aspiration pneumonia to be "death from age-related physical debility", and 10 (16%) have actually stated this on the death certificate. Advanced age, bedridden status, inability of oral intake and disturbance of consciousness including dementia were major factors in their decision-making. A total of 34 (55%) of the respondent physicians wanted detailed criteria to be established. Conclusions:  Physicians' attitudes toward the definition of "death from age-related physical debility" vary a great deal depending on the respondent. The description in death certificates therefore might inaccurately reflect the results of current mortality statistics in Japan. Geriatr Gerontol Int 2012; ••: ••-••.
    Geriatrics & Gerontology International 09/2012;
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    ABSTRACT: Objective: The aim of this study was to assess clinical and pulmonary thin-section CT findings in patients with acute Pseudomonas aeruginosa (PA) pulmonary infection.Methods: We retrospectively identified 44 patients with acute PA pneumonia who had undergone chest thin-section CT examinations between January 2004 and December 2010. We excluded nine patients with concurrent infections. The final study group comprised 35 patients (21 males, 14 females; age range 30-89 years, mean age 66.9 years) with PA pneumonia. The patients' clinical findings were assessed. Parenchymal abnormalities, enlarged lymph nodes and pleural effusion were evaluated on thin-section CT.Results: Underlying diseases included malignancy (n = 13), a smoking habit (n = 11) and cardiac disease (n = 8). CT scans of all patients revealed abnormal findings, including ground-glass opacity (n = 34), bronchial wall thickening (n = 31), consolidation (n = 23) and cavities (n = 5). Pleural effusion was found in 15 patients.Conclusion: PA pulmonary infection was observed in patients with underlying diseases such as malignancy or a smoking habit. The CT findings in patients with PA consisted mainly of ground-glass attenuation and bronchial wall thickening.Advances in knowledge: The CT findings consisted mainly of ground-glass attenuation, bronchial wall thickening and cavities. These findings in patients with an underlying disease such as malignancy or a smoking habit may be suggestive of pneumonia caused by PA infection.
    The British journal of radiology 07/2012; · 2.11 Impact Factor
  • International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 07/2012; · 2.17 Impact Factor
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    ABSTRACT: Lanosterol 14-α-demethylase ( Erg11 protein; Erg11p ), encoded by the ERG11 gene, is the primary target of azoles. Recently, a change in affinity of this enzyme for azoles has been reported as a resistance mechanism in several fungal species. Trichosporon asahii ( T. asahii) is susceptible to fluconazole (FLC). This report identified the ERG11 gene of T. asahii (NCBI accession; HQ176415). The Erg11p of T. asahii, presumed from the DNA sequence, was closely related to the Erg11p of Cryptococcus neoformans. Furthermore, a FLC-susceptible strain was cultured in medium containing FLC at concentrations from 4.0 to 16 μg mL(-1) in order to analyze the development of FLC resistance in T. asahii. The degree of resistance was related to the FLC concentration of the growth medium. One highly resistant strain that was cultured in the medium containing 16 μg mL(-1) FLC contained 1 point mutation (G1357C) that caused a single amino acid substitution at G453R. This amino acid is highly conserved among major fungal pathogens, and it is in a region very close to the heme-binding domain, which is characteristic of the cytochrome P450 superfamily, the primary target for the azole class of antifungal agents. This amino acid substitution may have caused the high resistance to azoles in T. asahii.
    FEMS Yeast Research 05/2012; 12(6):662-7. · 2.46 Impact Factor
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    ABSTRACT: Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.
    Clinical & Experimental Immunology 05/2012; 168(2):234-40. · 3.41 Impact Factor
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    ABSTRACT: Lanosterol 14‐α‐demethylase (Erg11 protein; Erg11p), encoded by the ERG11 gene, is the primary target of azoles. Recently, a change in affinity of this enzyme for azoles has been reported as a resistance mechanism in several fungal species. Trichosporon asahii ( T. asahii) is susceptible to fluconazole (FLC). This report identified the ERG11 gene of T. asahii (NCBI accession; HQ176415). The Erg11p of T. asahii, presumed from the DNA sequence, was closely related to the Erg11p of Cryptococcus neoformans. Furthermore, a FLC‐susceptible strain was cultured in medium containing FLC at concentrations from 4.0 to 16 μg mL−1 in order to analyze the development of FLC resistance in T. asahii. The degree of resistance was related to the FLC concentration of the growth medium. One highly resistant strain that was cultured in the medium containing 16 μg mL−1FLC contained 1 point mutation (G1357C) that caused a single amino acid substitution at G453R. This amino acid is highly conserved among major fungal pathogens, and it is in a region very close to the heme‐binding domain, which is characteristic of the cytochrome P450 superfamily, the primary target for the azole class of antifungal agents. This amino acid substitution may have caused the high resistance to azoles in T. asahii.
    FEMS Yeast Research 01/2012; 12(6). · 2.46 Impact Factor
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    ABSTRACT: More than 100000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare-associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP. Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community-acquired pneumonia (CAP) group (n = 123), a nursing home-acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O-HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality. Thirty-day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O-HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O-HCAP group. The NHAP group was clinically different from the O-HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O-HCAP.
    Respirology 05/2011; 16(5):856-61. · 2.78 Impact Factor
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    ABSTRACT: The environment surrounding influenza is changing in recent years. In the spring of 2009, pandemic (H1N1) 2009 occurred in Mexico, and became epidemic on a global scale thereafter. Therefore, control of influenza is very important all over the world. Now in Japan, four specific anti-influenza antiviral drugs are available: amantadine, oseltamivir, zanamivir and peramivir. Pandemic (H1N1) 2009 are amantadine-resistant viruses, thus is not recommended for use. Oseltamivir is most commonly used in Japan, however, we have to pay attention to oseltamivir-resistant influenza virus. Almost no zanamivir-resistant influenza virus has been so far reported. In Japan, peramivir is the first drip infusion medicine and is expected to be used in severe cases.
    Nippon rinsho. Japanese journal of clinical medicine 09/2010; 68(9):1679-84.
  • Internal Medicine 01/2010; 49(12):1251-2. · 0.97 Impact Factor
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    ABSTRACT: A 47-year-old man was admitted for further examination of uveitis. He had noticed scrotal swelling before his admission. A computed tomographic scan of the chest showed hilar and mediastinal lymphadenopathy, multiple micronodules and thickening of the interlobular septum, and these findings were consistent with sarcoidosis. Bronchoalveolar lavage fluid showed lymphocytosis. Gallium-67 scintigraphy revealed an abnormal accumulation in the hilar and mediastinal lymph nodes and in the bilateral scrotum. The resected and biopsied specimens of the epididymis and testis demonstrated numerous noncaseating epithelioid cell granulomas but no evidence of neoplasm. Therefore, systemic sarcoidosis was diagnosed. A review of the Japanese literature found most cases to be associated with a history of painless scrotal swelling with chest roentgenogram findings of stage I or II, while also indicating it was important to perform biopsy or surgically resect any epididymal and testicular lesion.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 08/2009; 47(7):631-5.

Publication Stats

289 Citations
90.73 Total Impact Points

Institutions

  • 1992–2014
    • Oita University
      • • Faculty of Medicine
      • • Department of Infectious Diseases
      • • Second Department of Internal Medicine
      Ōita, Ōita, Japan
  • 2013
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 2009
    • Oita Sanai Medical Centre
      Usuki, Ōita, Japan
  • 2006
    • Keio University
      Edo, Tōkyō, Japan