Issei Tokimatsu

Oita University, Ōita, Ōita, Japan

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Publications (96)113.69 Total impact


  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of the prophylactic administration of sulfamethoxazole-trimethoprim on the development of Pneumocystis pneumonia and airway colonization with Pneumocystis jirovecii in patients undergoing examinations to diagnose or rule out Pneumocystis pneumonia. Polymerase chain reaction was performed to detect Pneumocystis jirovecii using bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. Not all of the patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n=10) developed Pneumocystis pneumonia or demonstrated airway colonization with Pneumocystis jirovecii, and none of the patients who developed Pneumocystis pneumonia (n=11) or showed colonization (n=9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the Pneumocystis jirovecii DNA polymerase chain reaction, but all of 10 patients with prophylactic treatment showed negative results on it (Fisher's exact test, p=0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has possibilities to be effective in preventing Pneumocystis pneumonia as well as eliminating airway colonization with Pneumocystis jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.
    Preview · Article · Aug 2015
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    ABSTRACT: Teicoplanin (TEIC) is a glycopeptide currently used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). A plasma trough concentration (Cmin) of >20 mg/l should be used for severe infections. The aim of this study was to assess the efficacy, safety and use of Cmin >20 mg/l on day 4-6 in patients with complicated MRSA infections. Blood samples were drawn from the 41 included patients just before TEIC administration between day 4 and 6. The patients were divided into three groups (group A: >20 mg/l, group B: 10-20 mg/l and group C: <10 mg/l) based on their Cmin on day 4-6. Differences in efficacy between the groups were significant, but differences in safety were not. The patients in group A required lower cumulative doses than those in either groups B or C. The optimal clinical efficacy and safety might be associated with TEIC Cmin on the fourth to sixth day. © 2015 S. Karger AG, Basel.
    No preview · Article · Apr 2015 · Chemotherapy
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    ABSTRACT: To investigate the optimal dose of vancomycin (VCM) for methicillin-resistant Staphylococcus aureus infections in the urological patients including renal dysfunction. We had 143 sets of available data from the consecutive patients treated in the urological department for analysis in VCM dose, VCM trough and estimated glomerular filtration rate: eGFR at VCM trough examination. Patients were classified according to eGFR level, and we calculated the regression line between VCM dose and VCM trough accordingly. Median VCM dose were 1000 (range 500-3500) mg per day, the VCM trough was 15.6 ± 7.89 μg/ml, and eGFR was 61.1 ± 27.2 ml/min/1.73 m(2). Our regression analysis (x axis: VCM dose (mg) and y axis: VCM trough (μg/ml) was statistically significant in the group with eGFR of 30-60 ml/min/1.73 m(2) (y = 26.103x + 481.7; r (2) = 0.1291) and the group with eGFR of 60-90 ml/min/1.73 m(2) (y = 48.891x + 350.75; r (2) = 0.2561) in both with (p = 0.021 and 0.035, respectively) or without (p = 0.012 and 0.004, respectively) adjustments by body weight for VCM doses. These data showed that the optimal dose of VCM varied according to the eGFR value in consecutive urological patients with various renal functions.
    No preview · Article · Apr 2015 · International Urology and Nephrology
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    ABSTRACT: There are several mechanisms for antibiotic-resistant Pseudomonas aeruginosa. The purpose of this study is to investigate the association between the expression of efflux pump-coding genes and antibiotic resistance in P. aeruginosa causing urinary tract infections (UTIs). We extracted the RNA from 105 clinical strains of P. aeruginosa isolated from UTI patients with full data on antibiotic MICs and assayed real-time quantitative reverse-transcription PCR. We investigated the gene expressions of four resistance nodulation cell division-type multi-drug efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY(-OprA)) and the correlation of the MICs of nine antibiotics, risk factors and antibiotic resistance-related genes with expressions of mexB, mexC, mexE and mexY. Multivariate statistical data demonstrated a significant relationship between increased expression of mexB or mexC and complicated UTI (Odds ratio=8.03, P<0.001 and Odds ratio=8.86, P=0.032, respectively). We also found a significant association between the increased expression of mexC and resistance to levofloxacin (LVFX) (Odds ratio=4.48, P=0.035). In conclusion, increased expression of mexC leads to LVFX resistance in P. aeruginosa causing UTI. These results contribute to our knowledge of the efflux pump system and antibiotic resistance.The Journal of Antibiotics advance online publication, 8 April 2015; doi:10.1038/ja.2015.34.
    No preview · Article · Apr 2015 · The Journal of Antibiotics
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    Hisako Kushima · Issei Tokimatsu · Hiroshi Ishii · Jun-ichi Kadota
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    ABSTRACT: Most cases of deep-seated trichosporonosis develop in patients with neutropenia, but it has recently been reported that breakthrough infections with Trichosporon species can develop during the use of candin family of antifungal agents. This is due to the primary resistance of the causal fungus, Trichosporon asahii (T. asahii), to the candin agents. On the other hand, there has been a case report of infection with Trichosporon that presented high-level resistance to the azole family of antifungal agents. Therefore, the possibility that the frequent use of azole agents may lead to secondary resistance to these agents is a cause for concern. Since trichosporonosis is a relatively rare infectious disease, there has been no established breakpoint for this fungus to various antifungal agents, wherein we cannot precisely confirm its sensitivity or resistance to the agents. However, our experiment demonstrated one of the processes for acquired drug resistance, wherein the minimal inhibitory concentration of fluconazole for T. asahii was markedly elevated after its longterm in vitro exposure to the drug. Although the mechanisms for drug-resistance of Trichosporon species are unknown, it is supposed that they are the same as the mechanisms found in Candida and Aspergillus species, namely, modification of target molecules or decrease of access to the molecules. Since cases of trichosporonosis are likely to increase in the future, we believe that there is an urgent need to establish the breakpoint for T. asahii based on large-scale drug sensitivity tests, as well as to elucidate its drugresistance mechanisms. © 2015, Japanese Society for Medical Mycology. All rights reserved.
    Preview · Article · Jan 2015
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    ABSTRACT: An outbreak of Pseudomonas aeruginosa producing metallo–β-lactamase (MBLPA) in the hematology ward was controlled after use of toilet seats with bidet functions was terminated. Twenty four strains of MBLPA were identified from hospitalized patients in the hematology unit from January 2007 to December 2012. Multidisciplinary interventions including routine active surveillance, strengthening contact precautions, and analysis of risk factors for MBLPA were performed. However, new MBLPA infections continued to be identified after institution of infection control strategies. During the outbreaks, environmental surveys were conducted and 6 MBLPA isolates were detected from the spray nozzles of the toilet seats with bidet functions in this ward. Twenty four MBLPA isolates from the patients and 6 from spray nozzles were analyzed for chromosomal DNA typing by PCR–based ORF typing (POT). All 24 MBLPAs from the patients and all 6 isolates from nozzles had the same POTS patterns (Pot No. 644–41). Use of the toilet seats with bidet functions was discontinued during January to September 2013 and only 1 new isolate was identified in this period. Use of the toilet seats with bidet functions in October 2013 and 2 new MBLPAs were identified in only 3 months. Therefore, use of toilet seats with bidet functions was again terminated since January 2014 and occurrence of new isolates decreased again (1 isolate during 12 months). Incidence of MBLPA isolate per 1000 patient-days was 0.49 in the period of use of the toilet seats with bidet functions and 0.10 in the period of no use. In conclusion, use of toilet seats with bidet functions in the hematological unit is highly suspected as a risk factor for transmission of MBL producing Pseudomonas aeruginosa.
    Preview · Article · Jan 2015 · Japanese Journal of Environmental Infections
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    ABSTRACT: The target trough concentration of vancomycin in patients with febrile neutropenia has not been reported. The aim of this study was to estimate the target trough concentration for febrile neutropenia in patients with hematological malignancy. In this retrospective, single-center, observational cohort study, 63 hospitalized patients with hematological malignancy who were treated with vancomycin for febrile neutropenia due to bacteriologically documented or presumptive Gram-positive infections were analyzed. A significant difference in the first trough concentration of vancomycin was observed between the response and non-response groups, and between the nephrotoxicity and non-nephrotoxicity groups. Multiple logistic regression analyses identified the first trough concentration as the only independent variable associated with clinical efficacy and nephrotoxicity of vancomycin. The areas under the ROC curves were 0.72 and 0.83 for clinical efficacy and nephrotoxicity, respectively. The cut-off values of the first trough concentration were 11.1μg/ml for clinical efficacy (sensitivity 60%, specificity 87%) and 11.9μg/ml for nephrotoxicity (sensitivity 77%, specificity 82%). These results suggest a relationship of trough vancomycin concentration with clinical efficacy and incidence of nephrotoxicity. We propose a target trough vancomycin concentration of around 11.5μg/ml for febrile neutropenia in patients with hematological malignancy. Copyright © 2014. Published by Elsevier B.V.
    No preview · Article · Dec 2014 · Clinica Chimica Acta
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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.
    No preview · Article · Apr 2014 · Journal of Infection and Chemotherapy
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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.
    No preview · Article · Apr 2014 · Journal of Infection and Chemotherapy
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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.
    No preview · Article · Nov 2013 · Life sciences
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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: <4 μg/ml in the first TDM (group A, n=25), >4 μg/ml in the first and <4 μg/ml in the second TDM (group B, n=8), and >4 μg/ml in both first and second TDMs (group C, n=6). Results: Incidences of hepatotoxicity in groups A, B and C were 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 <4 μg/ml by dose adjustment after the initial TDM may reduce the incidence of hepatotoxicity in patients treated with voriconazole.
    No preview · Article · Jun 2013 · Clinica chimica acta; international journal of clinical chemistry
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    Full-text · Article · Jun 2013 · Blood Research
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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.
    No preview · Article · May 2013 · Journal of Infection and Chemotherapy
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    ABSTRACT: Arbekacin (ABK) was approved and widely used in Japan for treatment of patients infected with MRSA, and TDM was introduced in clinical practice. The Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring decided to develop a clinical practice guidelines for TDM of ABK for the following reasons. First, although the daily dose of 150-200 mg was approved in Japan, recent PK-PD studies revealed that higher serum concentration is required to achieve better clinical efficacy and several findings concerning the usefulness of higher dosage regimen have obtained recently. Second, although maximal concentrations that obtained immediately after the end of administration (Cmax) was generally adopted, the serum concentration at 1 h after initiation of administration [peak serum concentration (Cpeak)] proved to be more suitable as an efficacy indicator of aminoglycosides. Lastly, as ABK is approved only in Japan, no international practice guideline for TDM has not been available in ABK to date. This guideline evaluated the scientific data associated with serum ABK monitoring and provided recommendations based on the available evidence. Potential limitations of this guideline, however, include the findings that few prospective clinical trials of TDM of ABK are available in the treatment of MRSA infections and that most of the published literature describes observational studies.
    Full-text · Article · May 2013 · Journal of Infection and Chemotherapy
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    Full-text · Article · May 2013 · Journal of Infection and Chemotherapy
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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 (Cmin)/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC0-24)/MIC were observed between the response and non-response groups. Significant differences in Cmin and AUC0-24 were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of Cmin/MIC and AUC0-24/MIC for efficacy and of Cmin and AUC0-24 for safety of vancomycin. Conclusions: These results suggest little need to use peak concentration in vancomycin TDM because Cmin/MIC and Cmin are sufficient to predict the efficacy and safety of vancomycin.
    No preview · Article · Nov 2012 · Chemotherapy
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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.
    No preview · Article · Oct 2012 · The Annals of thoracic surgery
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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 2013; 13: 586–590.
    No preview · Article · Sep 2012 · Geriatrics & Gerontology International
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    F Okada · A Ono · Y Ando · T Nakayama · R Ishii · H Sato · A Kira · I Tokimatsu · J Kadota · H Mori
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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.
    Preview · Article · Jul 2012 · The British journal of radiology