{"created":"2023-06-19T07:18:27.482802+00:00","id":3823,"links":{},"metadata":{"_buckets":{"deposit":"fb935f4a-6154-4fc8-8f92-00a78d641068"},"_deposit":{"created_by":4,"id":"3823","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3823"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00003823","sets":["370:197:376"]},"author_link":["17707","17706"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2007-06-13"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"麻布大学"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(学術)"}]},"item_10006_description_22":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Adult periodontitis is an infectious disease caused by Gram-negative bacteria, especially specific anaerobic bacteria often found in the periodontal pocket.\n In the initial treatment of periodontitis, it is important to clean the crevice between the teeth and gums by mechanical means, such as scaling and root planing, and to remove such bacteria from the periodontal pocket, in which they are concentrated.\n Since 1990, treatment guidelines for periodontitis proposed that \"intrapocket antibiotic therapy\" be performed on refractory site of periodontitis after mechanical debridement in order to remove periodontopathic bacteria.\n However, there are few diagnostic methods to evaluate the efficacy of mechanical treatment to remove periodontopathic bacteria, and some diagnostic systems have problems such as sensitivity, identification, and handling.\n For intrapocket antibiotic therapy, tetracyclines are the most effective agents in the world. However in Japan, only 2% minocycline hydrochloride dental ointment is approved and can be used for treatment of periodontitis. In some cases, dentists cannot use the most appropriate antibiotic agent against causative bacteria even if they are identified.\n In addition, clinically, there are no guidelines for decision on use of antibiotics in treatment, and no information is available to make second selections of antibiotics when first antibiotics do not yield improvement.\n Since this situation will result in unnecessary overtreatment such as periodontal surgery or tooth loss, establishing a basic diagnosis and treatment system of chemotherapy is very important for this disease.\n The clinical utility of PadoTest[○!R], a diagnostic system using DNA/RNA probes, in determination of causative bacteria in the periodontal pocket in adult patients with periodontitis has recently been demonstrated. Taking these factors into consideration, (1) we used the PadoTest to examine whether causative bacteria were present in the periodontal pocket after treatment (and whether this system can be used for this purpose as well). (2) We administered 2% minocycline hydrochloride dental ointment in periodontal pockets with acute periodontal abscess and examined changes in bacterial load before to after treatment. (3) We also used various new quinolones and macrolides (which have been reported to be effective against biofilms) and determined their activities against bacteria causing periodontal disease. (4) In order to examine whether new quinolones and macrolides are useful in this clinical setting (i.e., periodontological treatment) by using clinical isolated strains from periodontal region.\n The following results were obtained.\n\n(1) To investigate changes in bacterial counts and flora from patients with acute periodontal abscess by the PadoTest. Results show the changes in total bacterial count in the test group (46 cases) and control group (45 cases) were 1.4×10^7 on day 0 and 4.4×10^6 on day 7 in the test group, and 1.4×10^7 on day 0 and 1.2×10^7 on day 7 in the control group, with significant decrease from day 0 to day 7 in both groups. Between-group comparison revealed no significant difference on day 0, though total bacterial count was significantly lower in the test group on day 7.\n\n(2) In patients with acute periodontal abscess, the (mean) periodontal pocket depth decreased from the baseline value after treatment in the test group, with significant improvement compared with the control group.\nChanges in rate of detection of four bacteria, Actinobacillus actinomycetemcomitans, Porphylomonas gingivalis, Treponema denticola, and Tannerella forsythia (Bacteroides forsythus) were determined before to after treatment. Rates of detection (%) were determined by dividing the number of sites positive for the four types of bacteria by the total number of sites examined.\nT. forsythia, P. gingivalis, and T. denticola were significantly lower on day 7 than on day 0 in the T group (p<0.01). A comparison of the T and C groups on day 7 showed that the rates of detection of T. forsythia, P. gingivalis, and T. denticola were significantly lower in the T group (p<0.01). No significant differences were observed in the rate of detection of A. actinomycetemcomitans before to after treatment within or between groups, probably because of low frequencies of detection and bacterial counts.\n\n(3) Minimum Inhibitory Concentration (MIC) of new-quinolone antibacterial reagents and macrolides antibiotics against a total of 21 bacterial species (18 oral related species and 3 control species) were determined. Of the four new quinolone agents tested, ofloxacin and levofloxacin were effective against P. gingivalis, Prevotella intermedia, P. melaninogenica, Fusobacterium nucleatum, Campylobactor rectus, Capnocytophaga gingivalis, and C. sputigena, with MIC ranges from <0.013 to 1.56 μg/mL. MIC values for specific bacterial species were as follows: for P. intermedia, both norfloxacine and levofloxacin exhibited an MIC of 0.013 μg/mL, while for Eikenella corrodens, ofloxacin, levofloxacin, and ciprofloxacin exhibited MICs of 0.025 to 0.05 μg/mL, indicating that both species are relatively sensitive to new quinolones. For A. actinomycetemcomitans, a species causing juvenile periodontitis, these new quinolone agents exhibited MICs of <0.013 to 0.2 μg/mL, and the MICs of levofloxacin and ciprofloxacin were especially low, at <0.013 μg/mL each. On the other hand, Lactobacillus spp. and Streptococcus spp., both of which are caries-causing bacteria often isolated from the oral cavity, were less sensitive to new quinolones, which exhibited MICs ranging from 1.56 to >25 μg/mL and from 0.39 to >25 μg/mL, respectively, than to minocycline (control drug), which exhibited MICs of 0.39 to 1.56 μg/mL against these species.\nMacrolides exhibited MICs of 0.05 to 0.78 μg/mL for the strains of P. gingivalis, and these MICs were worse than the 0.1 μg/mL MIC of minocycline. Macrolides exhibited MICs of 0.39 to 12.5 μg/mL and azithromycin 0.39 μg/mL for F. nucleatum.\n For A. actinomycetemcomitans strains, macrolides exhibited MICs of 0.1 to 6.25 μg/mL, slightly higher than that of minocycline (0.2 μg/mL). For other species related to periodontal disease, however, macrolides exhibited MIC values equivalent to that of minocycline. For Lactobacillus spp. and Streptococcus spp., on the other hand, macrolides exhibited low MIC values, ranging from 0.1 to 0.39 μg/mL and from 0.05 to 1.56 μg/mL, respectively.\n\n(4) MICs for clinical isolated bacterial strains derived from periodontal pockets of adult periodontitis patients, such as 20 strains of P. gingivalis and 7 strains of A. actinomycetemcomitans, were evaluated. The MIC_90 of macrolides included clarithromycin 0.1 μg/mL, roxithromycin 0.39 μg/mL, and azithromycin 1.56 μg/mL for P. gingivalis strains. The MIC_90 of new quinolones included levofloxacin and ciprofloxacin 6.25 μg/mL for P. gingivalis strains. Thus, the MIC_90 values of macrolides were 4- to 64-fold (or two to six 2-fold dilutions) lower than those of new quinolones for these clinically isolated strains. The MIC_90 of minocycline was 0.78 μg/mL, and this was high compared with the values for standard strains. The MIC_90s for clinical isolated strains were near those for standard strains for clarithromycin and roxithromycin. We then compared MIC_90 values of new quinolones and macrolides for clinical isolates of A. actinomycetemcomitans. The MIC_90 values of new quinolones were low, at 0.025 and 0.013 μg/mL for levofloxacin and ciprofloxacin, respectively, whereas those of macrolides were high, ranging from 3.13 to 25 μg/mL, indicating a marked difference between the two classes of antibiotics.\n\n These PadoTest findings indicated that \"intrapocket antibiotic therapy\" was significantly more effective than scaling and mouth-washing (the control procedure) in reducing total bacterial load in the periodontal pocket in patients with acute periodontal abscess.\n In addition, the PadoTest revealed that 3 species of periodontopathic bacteria, P. gingivalis, T. forsythia, and T. denticola, perform important roles in the acute phase periodontitis, as in adult periodontitis. In addition, the number of sites of detection for these 3 species was significantly decreased in the test group compared with the control group.\n For bacteria causing periodontal disease, on the other hand, the MICs of new quinolones were low. Levofloxacin and ciprofloxacin, in particular, exhibited significantly lower MIC values for A. actinomycetemcomitans or E. corrodens than those of other agents, suggesting the efficacy of these two drugs for treatment of patients with juvenile periodontitis.\n","subitem_description_type":"Other"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"成人性歯周炎の原因は口腔内グラム陰性桿菌、特に歯周ポケット内から検出される特異な嫌気性細菌が主体である。その歯周炎の初期治療では、歯周病菌が高密度に生息する歯周ポケット内の清掃を目的としてスケーリングやルートプレーニング等の機械的方法で歯牙と歯肉の微細な隙間を清掃することが重要である。しかし、その様な初期治療でも改善が見られない部位には、除菌を目的として抗生物質の歯周ポケット内局所投与を行うことが1990年以降、治療体系に組み込まれてきた。しかし、これらの治療で機械的清掃により原因菌がどの程度除去されたかを測定する手法が少なく、使用できる歯周病菌検査キットでも感度や菌種の特定、操作性は充分ではない。また、歯周病の治療においてテトラサイクリン系の薬剤が多く使用されているが、日本では2%塩酸ミノサイクリン軟膏以外に承認されている局所投与抗生物質はなく、検出された菌種に対応した薬剤選択が行えない。更に、臨床現場では抗生物質治療へ移行する判断基準や、抗生物質治療後改善が見られない場合の薬剤選択基準が確立されず、不必要な歯肉切除等の外科処置や抜歯など、オーバートリートメントが生じていることから、基本的な検査・治療体系を確立することが重要な課題となっている。そこで、筆者は診断システムであるDNA/RNAプローブを用いたPadoTestが成人性歯周炎における歯周ポケット内の原因菌検索に有用であることを加味して、今回、(1) 治療後の歯周ポケット内細菌の検索へのPadoTestを用いて応用の可能性を検討するとともに、(2) 急性歯周膿瘍における歯周ポケット内に2%塩酸ミノサイクリン軟膏の投与を行って、処置前後における菌の消長を検討した。さらに、(3) ニューキノロン系薬剤とバイオフィルムに対し効果の期待できるマクロライド系の抗生物質を用いて、歯周病の起因菌に対する抗菌力を測定し、臨床への応用の可能性を検討した。その概要は以下のとおりである。\n1. PadoTestを用いて、急性歯周膿瘍患者の治療前後における細菌叢の変化について検討した結果、試験群（46例）およびコントロール群（45例）の総菌数において、試験群では0日目1.4×10^7/サンプル（ペーパポイント#45番で採取したサンプル）、7日目4.4×10^6/サンプル、コントロール群では0日目1.4×10^7/サンプル、7日目1.2×10^7/サンプルであった。0日目と7日目の両群の比較では、試験群で処置後に菌数の低下が認められたが、コントロール群では菌量の差は認められなかった。また、0日目では群間比較において、菌量の差は認められなかった。しかし、7日目では試験群はコントロール群に比べて菌数が低下していることが明らかとなった。\n2. 急性歯周膿瘍患者の治療前後における臨床指標では、試験群では歯周ポケットの深さに改善が認められ、コントロール群に比べ優位に改善されていることが明らかとなった。また、処置前後におけるActinobacillus actinomycetemcomitans, Porphylomonas gingivalis, Treponema denticolaおよびTannerella forsythia (Bacteroides forsythus) の指標菌の合計4菌種の検出率変動では、T.forsythia, P.gingivalisおよびT.denticolaの3菌種の試験群で0日目に比べて7日目で有意 (p<0.01) に検出率が減少した。試験群とコントロール群の比較では、7日目の検出率においてT.forsythia, P.gingivalisおよびT.denticolaの3菌種は、試験群で有意に減少した。しかし、A.actinomycetemcomitansでは検出例数が少なく、両群間において差異は認めなかった。\n3. 口腔内細菌に対するニューキノロン系薬剤およびマクロライド系薬剤の抗菌力について、口腔内から分離頻度の高い18菌種およびコントロール3菌種の計21菌種の基準菌株を用いて、各種薬剤の最小発育阻止濃度 (MIC) 分布について検討した。今回供試した4種のニューキノロン系薬剤の中でOfloxacinとLevoflxacinはPorphyromonas gingivalis, Prevotella intermedia, P.melaninogenica, Fusobacterium nucleatum, Campylobactor rectus, Capnocytophaga gingivalis, C.sputigeneなどの歯周病関連菌株に対し<0.013～1.56μg/mlに分布し、低いMIC値を示した。また菌種別では、P.intermediaはNorfloxacinとLevofloxacinに対して0.013μg/ml、Eikenella corrodensはOfloxacin、LevofloxacinおよびCiprofloxacinに対して0.025～0.05μg/mlに分布し、低いMIC値を示した。一方、若年性歯周炎の原因菌であるActinobacillus actionmycetemcomitansは、いずれのニューキノロン系薬剤に対しても<0.013～0.2μg/mlに分布し、特にLevofloxacinとCiprofloxacinは<0.013と低いMIC値を示した。一方、ニューキノロン系薬剤は、口腔内から分離される齲蝕起因菌のLactobacillus属株に1.56～>25μg/ml、Streptococcus属株に0.39～>25μg/mlのMIC値を示したのに対し、対照薬剤であるMinocyclineはこれら両菌属株に0.39～1.56μg/mlのMIC値を示し、MIC値は劣っていた。P.gingivalis株では供試した4種のマクロライド系薬剤に対して0.05～0.78μg/mｌのMIC値を示し、対照薬剤であるMinocyclineの0.1μg/mlに比べ、高いMIC値であった。F.nucleatum株では、マクロライド系薬剤に0.39～12.5μg/ml、およびAzithromycinに0.39μg/mlのMIC値を示した。A.actinomycetemcomitans株では、マクロライド系薬剤に0.1～6.25μg/mlのMIC値を示し、Minocyclineの0.2μg/mlに比べやや高いMIC値を示した。しかし、その他の歯周病関連菌に対しては、マクロライド系薬剤はMinocyclineと同等のMIC値を示した。一方、Lactobacillus属株では0.1～0.39μg/ml、Streptococcus属株では0.05～1.56μg/mlのMIC値を示し、マクロライド系薬剤は低いMIC値を示した。\n4. 成人性歯周炎患者の歯周ポケットから分離したP.gingivalis 20株とA.actinomycetemcomitans 7株の合計27株の臨床分離株に対するMICの分布を測定した。その結果、P.gingivalisに対して各種薬剤をMIC_90で比較するとマクロライド系薬剤はClarithromycin 0.1μg/ml、Roxithromycin 0.39μg/mlおよびAzithromycin 1.56μg/mlを示し、ニューキノロン系薬剤のLevofloxacinやCiprofloxacinの6.25μg/mlと比較して2管から6管低いMIC値を示した。また、Minocyclineでは基準株0.1μg/mlに比べ臨床分離株は0.78μg/mlとMIC値が高かったが、ClarithromycinとRoxithromycinでは臨床分離株MIC値は基準株と類似していた。A.actinomycetemcomitansの臨床分離株に対する各種薬剤のMIC_90を比較したところ、ニューキノロン系薬剤ではLevofloxacin 0.025μg/ml、Ciprofloxacin 0.013μg/mlを示し、低いMIC値を示した。しかし、マクロライド系薬剤では本菌に対し3.13～25μg/mlとMIC_90値が高く、ニューキノロン系薬剤とは明らかに差異が認められた。\n　以上のことから、PadTestを用いた急性歯周膿瘍における局所投与抗生物質治療前後の歯周ポケット内総菌数について検討したところ、歯周ポケット内洗浄単独処置に比べ、局所投与抗生物質治療後に総菌数レベルが明らかに高い効果で低下することが明らかとなった。また、菌種別の検討では、P.gingivalis, T.forsythiaおよびT.denticolaの3菌種が歯周炎と同様に急性歯周膿瘍においても重要な役割を果たしていることが明らかとなった。さらに、試験群では歯周ポケット洗浄単独に比べて3菌種の検出率および検出部位数を有意に減少させていた。一方、抗生物質の歯周病原因菌に対するMIC値では、ニューキノロン系薬剤、特にLevofloxacinおよびCiprofloxacinがA.actinomycetemcomitansやE.corrodensに対してMIC値が低く、他の薬剤に比べ、優れていたことから若年性歯周炎患者の治療に有効であることが明らかとなった。\n","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"乙第14号"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"江口, 徹"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Eguchi, Toru","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2014-04-16"}],"displaytype":"detail","filename":"diss_de_otsu0014.pdf","filesize":[{"value":"3.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_de_otsu0014","url":"https://az.repo.nii.ac.jp/record/3823/files/diss_de_otsu0014.pdf"},"version_id":"8ab41b61-c95c-4922-80f8-d9541a8c7765"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2014-08-19"}],"displaytype":"detail","filename":"diss_de_otsu0014_jab&rev.pdf","filesize":[{"value":"388.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_de_otsu0014_jab&rev","url":"https://az.repo.nii.ac.jp/record/3823/files/diss_de_otsu0014_jab&rev.pdf"},"version_id":"2499662a-8dca-49c5-a8af-13af109a6677"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis"}]},"item_title":"成人性歯周炎の細菌学的診断とその治療における抗菌剤の選択","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"成人性歯周炎の細菌学的診断とその治療における抗菌剤の選択"},{"subitem_title":"Diagnosis of adult periodontitis based on bacterial detection and selection of antibiotics for treatment","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"4","path":["376"],"pubdate":{"attribute_name":"公開日","attribute_value":"2013-11-26"},"publish_date":"2013-11-26","publish_status":"0","recid":"3823","relation_version_is_last":true,"title":["成人性歯周炎の細菌学的診断とその治療における抗菌剤の選択"],"weko_creator_id":"4","weko_shared_id":4},"updated":"2023-06-19T08:14:33.716929+00:00"}