Papers - KAWAZOE Hitoshi

Problems associated with prophylactic use of erythromycin in 1566 staff to prevent hospital infection during the outbreak of pertussis

Tanaka H, Kaji M, Higuchi K, Shinohara N, Norimatsu M, Kawazoe H, Ninomiya M, Fukuoka N, Ishii N, Fujita J, Okabe A, Houchi H

Journal of Clinical Pharmacy and Therapeutics (WILEY)  34 ( 6 ) 719 - 722 2009.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0269-4727

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Background and objective: Pertussis developed in Kagawa University Medical School and University Hospital in May 2007. To control the outbreak and prevent the infection of hospital inpatients, the Infection Control Team (ICT) carried out the prophylactic administration of erythromycin (EM) to hospital staff (1566 staff) who might be exposed to Bordetella pertussis.
Methods: An oral dose of 1000 mg/day EM was given for 10 days. To assess compliance and estimate the frequency of adverse effect, the ICT conducted a questionnaire survey.
Results and discussion: Of 942 respondents (response rate: 60.2%), 264 (28.0%) experienced some form of EM adverse effects, of which the most commonly reported involved digestive organ symptoms, e.g. diarrhoea (15.6%), stomachache (7.5%), nausea (3.6%), epigastric distress (2.1%) and abdominal distention (1.8%). More importantly, 246 participants (26.1%) stopped taking the EM before completing 10 days because of perceived adverse effects.
Conclusion: These results indicate that EM appears to cause adverse effects more frequently than reported in the package insert in Japan. The prophylactic use of EM for pertussis infection is recognized in the guideline of the Centers for Disease Control and Prevention. However, this study suggests that attention should be paid to EM non-compliance during a pertussis outbreak, which could extend the duration of the outbreak and increase the number of affected patients.

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イトラコナゾール内用液がシクロスポリンの薬物動態に及ぼす影響

山口佳津騎, 河添　仁, 井上達也, 田中裕章, 二宮昌樹, 福岡憲泰, 芳地 一

日本病院薬剤師会雑誌 ((一社)日本病院薬剤師会)  45 ( 11 ) 1494 - 1496 2009.11

Research paper (scientific journal), Joint Work, Accepted

Comparison of Antibacterial Activity of Fluoroquinolones with Their Sucralfate-complexes against Clinically-isolated Bacteria

Kawazoe H, Takaoka K, Shibata H, Arakaki N, Higuti T, Negayama K, Houchi H, Tsuchiya K, Takiguchi Y

Journal of Health Science (The Pharmaceutical Society of Japan)  55 ( 5 ) 790 - 795 2009.10

Research paper (scientific journal), Joint Work, Lead author, Accepted

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Oral fluoroquinolones are widely known to form chelate complexes with metal-containing drugs, resulting in inhibition of their intestinal absorption. However, for intestinal sterilization, the concomitant regimen may be a selective and effective strategy due to decreased absorption of fluoroquinolones result in the retainment of antibiotics at the intestine if the mixture still perpetuated antibacterial activity. Therefore, to clarify whether the mixture of fluoroquinolones and sucralfate affects their antibacterial activity or not, we conducted in vitro study. According from the checkerboard study using a microdilution method with Mueller-Hinton broth, the antibacterial activity of these fluoroquinolones-sucralfate mixtures equaled to the parent fluoroquinolones even in the presence of sucralfate at the molar ratio of [sucralfate: fluoroquinolone] was less than 166, and the minimal inhibitory concentrations for clinical isolated Escherichia coli and Pseudomonas aeruginosa strains were independent of the existence of sucralfate. These data imply that the chelated forms of each fluoroquinolone retain antibacterial activity even in the presence of the recommended therapeutic doses of sucralfate in clinical practice.

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薬学生の満足度調査から見えてきた薬剤師教育の不足項目 -実務実習事前教育の現状-

河添　仁, 福岡憲泰, 辻　繁子, 合田哲子, 安西英明, 芳地　一

医療薬学 ((一社)日本医療薬学会)  35 ( 7 ) 501 - 508 2009.07

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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Little information is available on the level of satisfaction of pharmacy students with pharmacist education before clinical pharmacy practice,although the current pharmacy education is rapidly changing to place more importance on nurturing clinical experts.In view of this,we performed a questionnaire survey to investigate deficiencies in pharmacist education that affected the satisfaction level of pharmacy students.A questionnaire was given to 59 pharmacy students between February 2007 and July 2008 and the responses were analyzed using categorical regression in order to objectively reflect the results in future pharmacist education.The survey revealed that pharmacist jobs that reduced the satisfaction level of pharmacy students included“making in-hospital pharmaceutical preparations”,“compliance management”,“clinical research coordination”,“drug purchasing management and stock control”,and“payment for injection drugs”,etc.,listed in order of degree of deficiency.Other items that influenced the satisfaction level were“nurturing medical professionals”,“team approach to medical treatment”,and“communication”.In this regard,75.4% of the pharmacy students responded that communication education between pharmacists and other medical staff was insufficient.The findings of our survey suggest that satisfaction level is a useful index to target in improving pharmacist education.

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Prospective Study to Assess the Optimal Blood Concentration of Tacrolimus in Japanese Patients with Rheumatoid Arthritis

Kawazoe H, Dobashi H, Kameda T, Susaki K, Kittaka K, Tokuda M, Fukuoka N, Ishida T, Takiguchi Y, Houchi H

Journal of Health Science (The Pharmaceutical Society of Japan)  55 ( 3 ) 435 - 440 2009.06

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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We performed a prospective study to assess the optimal blood concentration of tacrolimus in Japanese patients with rheumatoid arthritis (RA). The dose of tacrolimus (1-3mg/day) was administered orally once daily after the evening meal, and the blood concentration of tacrolimus 12 hr after administration was quantified. A total of 23 patients were enrolled. Clinical efficacy was assessed using the Disease Activity Score in 28 joints and European League Against Rheumatism (EULAR) response criteria at each outpatient visit during months 1-6. The ratio of patients who showed a moderate or good response was 47.8% (11/23). The mean blood concentrations of tacrolimus in EULAR responders and EULAR non-responders were 5.5±3.6 (mean±S.D.) and 3.1±1.9 ng/ml, respectively (p=0.069). Interestingly, although tacrolimus had lower mean blood concentrations (<5 ng/ml) compared with transplant fields (10-20 ng/ml), six (35.3%) of 17 patients showed sufficient response to tacrolimus. In addition, in five patients, tacrolimus was co-administered with methotrexate (MTX). On the other hand, the mean blood concentrations of tacrolimus in patients who did or did not develop adverse events were 4.8±4.4 (n=8) and 4.0±2.1 (n=15) ng/ml, respectively (p=0.624). We failed to clear the optimal blood concentration of tacrolimus in RA patients, but one of the most remarkable findings was the observation that patients in whom tacrolimus was combined with MTX reached a positive response at much lower tacrolimus concentrations compared to patients not co-treated with MTX.

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精神科病棟における薬剤師の役割―医師・看護師への認識調査の前後比較による検証と再評価―

篠原尚樹, 河添　仁, 田中裕章, 二宮昌樹, 福岡憲泰, 芳地　一

日本病院薬剤師会雑誌 ((一社)日本病院薬剤師会)  45 ( 4 ) 511 - 514 2009.04

Research paper (scientific journal), Joint Work, Accepted

同種造血幹細胞移植患者における多剤耐性緑膿菌による感染症治療

河添　仁, 滝口祥令, 井上達也, 山口佳津騎, 田中裕章, 加地雅人, 辻　繁子, 二宮昌樹, 福岡憲泰, 大西宏明, 石田俊彦, 芳地　一

Yakugaku Zasshi ((公社)日本薬学会)  128 ( 4 ) 657 - 661 2008.04

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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Infections caused by multiple-drug-resistant Pseudomonas aeruginosa (MDRP) are a clinically significant problem. We reported here the effective use of combination therapy in a patient with infection caused by MDRP according to an interventional treatment strategy suggested by a pharmacist. The patient was a 70-year-old male who underwent allogeneic hematopoietic stem cell transplantation. On day 45 after transplant, MDRP was newly isolated from urine, but the diagnosis at that time was colonization. On day 61, the patient developed a fever (≥38.0°C). In addition, laboratory data showed that C-reactive protein (CRP) was also increased. At the medical team conference, the pharmacist proposed the following treatment strategy for this infection. Aztreonam and amikacin were intravenously administered at doses of 2 g/day and 800 mg/day, respectively. The subsequent clinical course was well controlled, but the infection recurred and was aggravated. Aztreonam and ciprofloxacin were then intravenously administered at doses of 4 g/day and 600 mg/day, respectively, resulting in the alleviation of fever in the patient as well as a decrease in CRP and disappearance of MDRP isolates from urine on day 67; that is, MDRP infection was consequently well controlled. In conclusion, the combination therapy between aztreonam and amikacin, or ciprofloxacin may be clinically useful for severe infections of MDRP in compromised hosts.

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院内製剤抗生物質点眼液の安定性

田中裕章, 朝倉正登, 土居智明, 河添　仁, 福岡憲泰, 玉井栄治, 宮田　茂, 松下　治, 岡部昭延, 芳地　一

日本病院薬剤師会雑誌 ((一社)日本病院薬剤師会)  43 ( 10 ) 1369 - 1372 2007.10

Research paper (scientific journal), Joint Work, Accepted

同種造血幹細胞移植患者におけるニューキノロン系抗菌薬による内因性感染の予防効果 —骨髄移植，末梢血幹細胞移植，臍帯血移植の比較—

河添　仁, 滝口祥令, 田中裕章, 二宮昌樹, 福岡憲泰, 大西宏明, 石田俊彦, 芳地　一

Yakugaku Zasshi ((公社)日本薬学会)  127 ( 8 ) 1301 - 1307 2007.08

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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We performed a retrospective study to examine the preventive effects of newquinolones for endogenous infection in patients receiving various allogeneic hematopoietic stem cell transplantation including bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT). Forty-nine patients were enrolled. Ciprofloxacin or norfloxacin was orally administered for intestinal sterilization from day -14 until engraftment. As a result, the period from transplantation until engraftment was significantly longer in CBT group than in BMT group. The febrile index (the ratio of the febrile (≥38.0°C) period during neutropenia (≤500 cells/mm3) and C-reactive protein (CRP)-positive index (the ratio of CRP-positive (≥2.0 mg/dl) period during neutropenia) were comparable among the three groups. In addition, no gram-negative bacteria in stool was isolated in the three groups; that is, an endogenous infection of gram-negative bacteria, a potential pathogen, was well controlled by newquinolones. We should be careful when interpreting the results of this small study; however, newquinolones are clinically effective for endogenous infection of gram-negative bacteria in patients receiving not only BMT, but also PBSCT and CBT.

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個々の患者の副作用予測のために開発された婦人科がん化学療法モニタリングシート

土居智明, 飯原なおみ, 河添　仁, 福岡憲泰, 芳地　一, 黒崎勇二, 森田修之

Yakugaku Zasshi ((公社)日本薬学会)  127 ( 6 ) 1027 - 1033 2007.06

Research paper (scientific journal), Joint Work, Accepted

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Monitoring the adverse reaction patterns specific to individual patients is important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often implemented repeatedly with an altered protocol during prolonged terms. The purpose of this study was to develop and assess the efficacy of a worksheet that pharmacists can use to analyze adverse reaction patterns in individual patients with gynecologic chemotherapy. The worksheet which we developed consisted of multiple sections. One section is for necessary drug information for the proper use of antineoplastic agents. Another section is for the following items recorded by the pharmacists: a) patients' basic information such as stage of disease and protocol, b) state of implementation and break of chemotherapy and supportive therapy on calendar, and c) laboratory data and symptoms. We arranged the last item below the calendar and enabled pharmacists to easily assess individual adverse reactions coupled with the treatment course. Reviews of the developed worksheet indicated that the worksheet led to the convenient detection of individual adverse reaction patterns and effective prevention of additional adverse reactions. This monitoring sheet covering long-term chemotherapy which was designed to predict individual adverse reaction patterns will improve the individualization and safety of gynecologic chemotherapy.

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Preventive Effects of Low-dose Dexamethasone for Delayed Adverse Events Induced by Carboplatin-based Combination Chemotherapy

Kawazoe H, Takiguchi Y, Tanaka H, Doi C, Fukuoka N, Kanaji N, Bandoh S, Ishida T, Houchi H

Yakugaku Zasshi ((公社)日本薬学会)  127 ( 6 ) 1001 - 1006 2007.06

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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We performed a retrospective study to examine the protective effect of low-dose dexamethasone (DEX) on delayed adverse events induced by carboplatin (CBDCA)-based combination chemotherapy in patients with thoracic tumors. Low-dose DEX (4-8 mg/day) was administered on day 1 and after, in addition to a serotonin 5-HT3 receptor antagonist. The acute adverse events (day 1) were well controlled in the patients with or without co-treatment of DEX. On the other hand, the delayed nausea, emesis, anorexia, and fatigue after day 2 failed to be controlled by 5-HT3 antagonist alone. Co-treatment with DEX significantly suppressed the grade of the delayed adverse events during days 2-10. The mean ratio of complete protection during days 2-10 were significantly higher in the DEX-treated group compared with the non-DEX-treated group. These results reveal that low-dose DEX is a clinically effective treatment for the prevention of delayed adverse events induced by CBDCA-based combination chemotherapy.

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Change of the Blood Concentration of Tacrolimus after the Switch from Fluconazole to Voriconazole in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Kawazoe H, Takiguchi Y, Tanaka H, Fukuoka N, Ohnishi H, Ishida T, Houchi H

Biological and Pharmaceutical Bulletin (The Pharmaceutical Society of Japan)  29 ( 12 ) 2528 - 2531 2006.12

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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The purpose of this study was to assess the impact by switching co-administered triazole antifungal agent from fluconazole (FCZ) to voriconazole (VCZ) on the blood concentration of tacrolimus (FK506) in patients receiving allogeneic hematopoietic stem cell transplantation. We performed a retrospective study presented as case reports. The blood concentration of FK506 was increased after the switch from FCZ to VCZ, resulting in increase of the concentration/dose (C/D) ratio of FK506. Thus, the mean C/D ratios of FK506 with oral administration was surprisingly increased over 4.5-fold after the switch. Therefore, it was necessary to reduce the FK506 dose when co-administered FCZ is switched to VCZ. We should be careful when interpreting the results of these case reports; however, in some patients, it is recommended that the dose of FK506 be reduced to one-fifth after the switch.

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患者参加型癌化学療法副作用モニタリング—患者の治療参加と情報の共有化—

河添　仁, 久保智美, 飯原なおみ, 土居智明, 奥條真紀子, 福岡憲泰, 藤本さとし, 金地伸拓, 坂東修二, 石田俊彦, 滝口祥令, 芳地　一

Yakugaku Zasshi ((公社)日本薬学会)  126 ( 8 ) 629 - 642 2006.08

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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The purpose of this study was to assess patient participation in cancer therapy and the sharing of patient information among the medical care team (physicians, nurses, pharmacists, and especially patients). We monitored the side effects of cancer chemotherapy with patients, and developed two support tools: One scored the points of subjective symptoms (fatigue, anorexia, nausea, etc) by patients, and the other recorded objective symptoms (clinical examination data) by pharmacists. It is most important that they attend each patient at their bedside. At this time, the trial was evaluated by questionnaire survey by inpatients receiving cancer chemotherapy (n=15). As a result, all patients (15/15) responded that this trial was necessary. This trial addressed the following: 1) increased communication between patients and medical staff concerning side effects (14/15), 2) increased interest in side effects (10/15), 3) when a patient tells medical staff about side effects, they act on it (10/15). None of the patients felt inconvenienced by scoring every day (0/15), or anxiety about side effects (0/15). Furthermore, all patients (15/15) responded that “participation of pharmacists in cancer chemotherapy” was necessary. This trial revealed no problems and suggested that patients related to the center of medical care. We should be careful in interpreting results of this small sized trial; however, the following conclusions should be reached: 1) introduction of monitoring side effects of cancer chemotherapy with patients, 2) develop communication among the medical care team.

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診療報酬改訂に伴う「投与日数規制の原則廃止」の薬物療法管理に及ぼす影響

河添　仁, 飯原なおみ, 土居智明, 森田修之

Yakugaku Zasshi ((公社)日本薬学会)  125 ( 12 ) 959 - 969 2005.12

Research paper (scientific journal), Joint Work, Lead author, Accepted

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The proclamation of April 2002 of a Ministry of Health, Labor and Welfare ordinance has enabled doctors to prescribe drugs for an outpatient without a limit on the length of prescription terms except for a few drugs. There is a concern that the prescription-term deregulation could cause careless drug therapy management in order to extend the interval between patient hospital visits. The purpose of this study is to make pre- and post-deregulation comparisons of two items, prescription terms and implementation of clinical examination that complied with package-insert precautions, and to discuss the approaches to increase safety. Prescription terms have lengthened progressively. In the pre-regulation period of January to March 2002, the mean prescription term was 19.9 days; in the post-regulation period of July to September 2002, it was 24.9 days; and in July to September 2003, 28.6 days. Even for anti-tumor agents, there were prescriptions over 90 days after deregulation. There was no significant difference between the pre- and post-deregulation compliance ratios for the package-insert precautions in eight drugs of investigated nine. However, one case had a delay in detection of liver dysfunction, which was caused by deviation from the once-a-month testing indicated in the package-insert precautions for prolonged prescription terms. The evidence suggested that the deregulation led to negligent drug therapy management. To assure safe therapy, the following should be addressed: first, sufficient function of a computerized prescriber order entry system and second, creation of a new framework with pharmacists' active involvement such as collaborative therapy management with physicians.

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