今日の臨床サポート

感染性腸炎

著者: 大川清孝 大阪市立十三市民病院 消化器内科

監修: 上村直実 国立国際医療研究センター 国府台病院

著者校正/監修レビュー済:2021/11/02
患者向け説明資料
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
大川清孝 : 特に申告事項無し[2021年]
監修:上村直実 : 未申告[2021年]

改訂のポイント:
  1. JAID/JSC 感染症治療ガイドライン 2015 ―腸管感染症―に基づいて抗菌薬治療やウイルス性腸炎の診断を改定した。
  1. Clostridium difficileClostridioides difficile(C.difficile)に変更した。
  1. Clostridioides difficile(Clostridium)感染症診療ガイドラインが2018年10月に発刊されたため紹介した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 感染性腸炎とは病原体(微生物)の感染により下痢・嘔吐が引き起こされた疾患である。
  1. 原因となる病原体は多種多様である。
  1. 感染性腸炎を起こす代表的な病原体(原因食、潜伏期、血便・腹痛・発熱の有無):表<図表>
  1. 感染性腸炎を起こす病原体ではヒト-ヒト感染(伝染)を高頻度に起こすものもからまったく起こさないものまでさまざまである。
  1. 感染性腸炎の抗菌薬治療は多様な原因微生物と伝染程度の異なりから一定ではない。
  1. 食中毒は経口的に侵入した病原体・毒素・薬物などさまざまな原因物質で起こる疾患の総称である。食中毒の症状は下痢・嘔吐のみでなく、神経症状などを含めて多様である。
  1. 感染症法での届出と食中毒の届出は別個に行われる。
 
法律に関する規制:
  1. 感染症法による規制では、コレラ、細菌性赤痢、腸管出血性大腸菌感染症、腸チフス、パラチフスは、3類感染症に分類され、診断した医師は、ただちに最寄の保健所に届け出、また必要に応じて患者及び無症状病原体保有者について就業制限等の措置をする必要がある。また、アメーバ赤痢は、5類感染症(医師による届け出)に分類され、診断した医師は、7日以内に最寄の保健所に届け出る必要がある。また、ロタウイルスによる感染性胃腸炎は、5類感染症定点把握疾患に定められており、全国約500カ所の基幹定点から毎週報告がなされている。
  1. また、学校保健安全法では、コレラ、細菌性赤痢、腸管出血性大腸菌感染症、腸チフス、パラチフスは、第三種感染症に指定されており、「病状により学校医その他の医師において感染のおそれがないと認めるまで」を出席停止の期間の基準としている。
  1. 食品衛生法では、食品、添加物、器具若しくは容器包装に起因して中毒した患者若しくはその疑いのある者(以下「食中毒患者等」という。)を診断し、又はその死体を検案した医師は、直ちに最寄りの保健所長にその旨を届け出なければならない( 食中毒患者の届出の義務 )。
問診・診察のポイント  
  1. 診察ポイントは症状(急性の下痢・嘔吐)の原因が感染か、感染以外かを想定することである。感染以外では病原体以外の食中毒、薬剤性、食物アレルギー、虚血性腸疾患、炎症性腸疾患初期などがある。なお、赤痢アメーバや他の腸管寄生虫疾患では慢性下痢が生じる。

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文献 

著者: J E Kaplan, R Feldman, D S Campbell, C Lookabaugh, G W Gary
雑誌名: Am J Public Health. 1982 Dec;72(12):1329-32. doi: 10.2105/ajph.72.12.1329.
Abstract/Text Records of 642 outbreaks of acute gastroenteritis were reviewed to determine the proportion of outbreaks that were clinically and epidemiologically consistent with Norwalk-like virus infection. Using as our criteria stool cultures negative for bacterial pathogens, mean (or median) duration of illness 12-60 hours, vomiting in greater than or equal to 50 per cent of cases, and, if known, mean (or median) incubation period of 24-48 hours, we found that 23 per cent of waterborne outbreaks, 4 per cent of foodborne outbreaks, and 67 per cent, 60 per cent, and 28 per cent of outbreaks in nursing homes, in summer camps, and on cruise ships, respectively, satisfied the criteria for Norwalk-like pattern. Of 54 outbreaks that satisfied the criteria for Norwalk-like pattern, 14 were investigated for virus etiology. Ten of these (71 per cent) yielded serologic evidence of Norwalk-like virus infection. Norwalk-like viruses are probably an important cause of outbreaks of acute gastroenteritis. Investigation for Norwalk virus antibody in outbreaks that are clinically and epidemiologically consistent with Norwalk-like virus infection is likely to yield diagnostically useful results.

PMID 6291414  Am J Public Health. 1982 Dec;72(12):1329-32. doi: 10.21・・・
著者: Fernanda C Lessa, Yi Mu, Wendy M Bamberg, Zintars G Beldavs, Ghinwa K Dumyati, John R Dunn, Monica M Farley, Stacy M Holzbauer, James I Meek, Erin C Phipps, Lucy E Wilson, Lisa G Winston, Jessica A Cohen, Brandi M Limbago, Scott K Fridkin, Dale N Gerding, L Clifford McDonald
雑誌名: N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.
Abstract/Text BACKGROUND: The magnitude and scope of Clostridium difficile infection in the United States continue to evolve.
METHODS: In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥ 1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection.
RESULTS: A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001).
CONCLUSIONS: C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

PMID 25714160  N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/N・・・
著者: Fekety R R, McFarland L V LV, Surawicz C M CM, Greenberg R N RN, Elmer G W GW, Mulligan M E ME
雑誌名: Clin Infect Dis. 1997 Mar;24(3):324-33.
Abstract/Text Recurrent Clostridium difficile diarrhea (RCDD) occurs in 20% of patients after they have received standard antibiotic treatment with vancomycin or metronidazole, but the reasons for the recurrences are largely unknown. Patients receiving vancomycin or metronidazole for active C. difficile diarrhea (CDD) were referred to our study centers for treatment and a 2-month follow-up as part of a randomized placebo-controlled trial. Sixty patients had RCDD (median number of episodes, 3.0; range, 2-9 episodes) and 64 were having their first episode of CDD. Patients with RCDD had more-severe abdominal pain and were more likely to have fever but initially responded well to antibiotic therapy. Data on sequential episodes showed no progression in disease severity. Five factors were associated with a higher risk of RCDD: the number of previous CDD episodes, onset of the initial disease in the spring, exposure to additional antibiotics for treatment of other infections, infection with immunoblot type 1 or 2 strains of C. difficile, and female gender. These factors may help to identify patients who are more likely to develop RCDD and require careful medical supervision.

PMID 9114180  Clin Infect Dis. 1997 Mar;24(3):324-33.
著者: Els van Nood, Anne Vrieze, Max Nieuwdorp, Susana Fuentes, Erwin G Zoetendal, Willem M de Vos, Caroline E Visser, Ed J Kuijper, Joep F W M Bartelsman, Jan G P Tijssen, Peter Speelman, Marcel G W Dijkgraaf, Josbert J Keller
雑誌名: N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
Abstract/Text BACKGROUND: Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection.
METHODS: We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube; a standard vancomycin regimen (500 mg orally four times per day for 14 days); or a standard vancomycin regimen with bowel lavage. The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks.
RESULTS: The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species.
CONCLUSIONS: The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin. (Funded by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research; Netherlands Trial Register number, NTR1177.).

PMID 23323867  N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/N・・・
著者: Giovanni Cammarota, Gianluca Ianiro, Antonio Gasbarrini
雑誌名: J Clin Gastroenterol. 2014 Sep;48(8):693-702. doi: 10.1097/MCG.0000000000000046.
Abstract/Text GOAL: By systematic review, we assessed the impact of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile (CD)-associated diarrhea.
BACKGROUND: Fecal microbiota microbiota transplantation from a healthy donor into an individual with CD infection (CDI) can resolve symptoms.
STUDY: We conducted systematic searches in PubMed, SCOPUS, Web of Science, and Cochrane Library. The last search was run on February 8, 2013. The following Medical Subject Headings terms and keywords were used alone or in combination: Clostridium difficile; Clostridium infection; pseudomembranous colitis; feces; stools; fecal suspension; fecal transplantation; fecal transfer; fecal infusion; microbiota; bacteriotherapy; enema; nasogastric tube; colonoscopy; gastroscopy; fecal donation; donor. A critical appraisal of the clinical research evidence on the effectiveness and safety of FMT for the treatment of patients with CD-associated diarrhea was made.
RESULTS: Twenty full-text case series, 15 case reports, and 1 randomized controlled study were included for the final analysis. Almost all patients treated with donors' fecal infusion experienced recurrent episodes of CD-associated diarrhea despite standard antibiotic treatment. Of a total of 536 patients treated, 467 (87%) experienced resolution of diarrhea. Diarrhea resolution rates varied according to the site of infusion: 81% in the stomach; 86% in the duodenum/jejunum; 93% in the cecum/ascending colon; and 84% in the distal colon. No severe adverse events were reported with the procedure.
CONCLUSIONS: FMT seems efficacious and safe for the treatment of recurrent CDI. Hospitals should encourage the development of fecal transplantation programs to improve therapy of local patients.

PMID 24440934  J Clin Gastroenterol. 2014 Sep;48(8):693-702. doi: 10.1・・・
著者: Christine H Lee, Theodore Steiner, Elaine O Petrof, Marek Smieja, Diane Roscoe, Anouf Nematallah, J Scott Weese, Stephen Collins, Paul Moayyedi, Mark Crowther, Mark J Ropeleski, Padman Jayaratne, David Higgins, Yingfu Li, Neil V Rau, Peter T Kim
雑誌名: JAMA. 2016 Jan 12;315(2):142-9. doi: 10.1001/jama.2015.18098.
Abstract/Text IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention.
OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada.
INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema.
MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%.
RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups.
CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.
TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.

PMID 26757463  JAMA. 2016 Jan 12;315(2):142-9. doi: 10.1001/jama.2015.・・・
著者: Ilan Youngster, George H Russell, Christina Pindar, Tomer Ziv-Baran, Jenny Sauk, Elizabeth L Hohmann
雑誌名: JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.
Abstract/Text IMPORTANCE: Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.
OBJECTIVE: To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection.
DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled.
INTERVENTIONS: Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.
MAIN OUTCOMES AND MEASURES: The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.
RESULTS: No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02).
CONCLUSIONS AND RELEVANCE: This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01914731.

PMID 25322359  JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014・・・
著者: Johan S Bakken, Thomas Borody, Lawrence J Brandt, Joel V Brill, Daniel C Demarco, Marc Alaric Franzos, Colleen Kelly, Alexander Khoruts, Thomas Louie, Lawrence P Martinelli, Thomas A Moore, George Russell, Christina Surawicz, Fecal Microbiota Transplantation Workgroup
雑誌名: Clin Gastroenterol Hepatol. 2011 Dec;9(12):1044-9. doi: 10.1016/j.cgh.2011.08.014. Epub 2011 Aug 24.
Abstract/Text Clostridium difficile infection is increasing in incidence, severity, and mortality. Treatment options are limited and appear to be losing efficacy. Recurrent disease is especially challenging; extended treatment with oral vancomycin is becoming increasingly common but is expensive. Fecal microbiota transplantation is safe, inexpensive, and effective; according to case and small series reports, about 90% of patients are cured. We discuss the rationale, methods, and use of fecal microbiota transplantation.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 21871249  Clin Gastroenterol Hepatol. 2011 Dec;9(12):1044-9. doi:・・・
著者: Shigeki Bamba, Atsushi Nishida, Hirotsugu Imaeda, Osamu Inatomi, Masaya Sasaki, Mitsushige Sugimoto, Akira Andoh
雑誌名: J Microbiol Immunol Infect. 2017 Nov 5;. doi: 10.1016/j.jmii.2017.08.027. Epub 2017 Nov 5.
Abstract/Text We prospectively enrolled four Japanese patients with refractory Clostridium difficile infection (CDI) and were treated with a single fecal microbiota transplantation (FMT). The average age of the patients was 83.7 years. All patients had a successful clinical course for up to 3 months without any adverse events.

Copyright © 2017. Published by Elsevier B.V.
PMID 29158082  J Microbiol Immunol Infect. 2017 Nov 5;. doi: 10.1016/j・・・

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