今日の臨床サポート

旅行者下痢症

著者: 竹下望 国立感染症研究センター 研究企画調整センター

監修: 大曲貴夫 国立国際医療研究センター

著者校正済:2022/02/16
現在監修レビュー中
参考ガイドライン:
  1. 厚生労働省健康局結核感染症課:抗微生物薬適正使用の手引き第2版 2019年
  1. 米国感染症学会(IDSA):2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea
  1. 日本感染症学会日本化学療法学会 JAID/JSC 感染症治療ガイド・ガイドライン作成委員会:JAID/JSC 感染症治療ガイドライン2015
患者向け説明資料

概要・推奨   

  1. 消化管感染症以外の感染症も下痢症状を起こし得るため、発熱を認める場合は、熱帯熱マラリア、デング熱等の疾患を常に鑑別に入れることが強く推奨される(推奨度1)
  1. 腸チフス、パラチフスの流行地域への流行地域への渡航歴があり、発熱がある場合は下痢の有無にかかわらず、腸チフスとパラチフスを鑑別に入れる必要がある(推奨度1/G
  1. 多くの治療が必要ではない旅行者下痢症においては、検査は推奨されない。SalmonellaShigellaCampylobacterE.coli、O157を考慮するような場合は便培養を行う。
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  1. 症状が遷延する場合は原虫・寄生虫検査を実施。8〜12週以内に抗菌薬投与歴がある場合は、Clostridium difficile toxin A+Bを検査する。また炎症性腸疾患、postinfectious irritable bowel syndrome も考慮する(推奨度2/G)
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  1. 東南アジアからの帰国者ではCampylobacterの頻度が高いため、治療を行う場合には、推定起炎菌として考慮する必要がある(推奨度2/J)。(抗菌薬使用時にはカバーを考慮する)
  1. アジスロマイシン500mg 1回投与は旅行者下痢症に効果がある。本邦では、アジスロマイシンの保険適応はないが、東南アジアからの帰国の患者はキノロン耐性のCampylobacterの保有有率が多いため、アジスロマイシンにて治療することはおそらく推奨される(推奨度2)
  1. Campylobacterの抗菌薬耐性化は開発途上国で進んでおり、特にキノロン系抗菌薬に対して進んでいる。したがって、Campylobacterの頻度が高い地域で、治療対象として考慮する場合は、シプロフロキサシンを旅行者下痢症のfirst choiceとすることはおそらく推奨されない(推奨度3)
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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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
竹下望 : 未申告[2022年]
監修:大曲貴夫 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを実施し、掲載フォーム変更に合わせた記載の修正を実施した。

病態、疫学、診察

疾患情報  
  1. 旅行者下痢症は、発展途上国に渡航した際に認められる健康問題の中で最も多い。旅行者の30~40%が罹患するとされる。帰国後に健康問題を訴えて国際医療センターで受診した1,449人中、31%が旅行者下痢症であった。
  1. 古典的な旅行者下痢症の定義は、海外渡航中または帰国後短期に、1日3回以上の非有形便を認めることである。
  1. 感染経路は水、食事が主である。
  1. 細菌、ウイルス、寄生虫など原因となる病原体は多様だが、毒素原生大腸菌(enterotoxigenic Escherichia coli、ETEC)が最多である。
  1. 旅行者下痢症は一般的に自然経過で改善するため、輸液や電解質補正による対症療法が重要である。ただし症状が持続する場合や症状が強い場合には、抗菌薬投与を行う。
  1. 発熱を伴う場合、下痢症状を認めても全身性発熱疾患の鑑別を行う。
問診・診察のポイント  
  1. 脱水の程度を速やかに評価し、経静脈的に輸液を行うべきか判断する。

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文献 

R L Guerrant, T Van Gilder, T S Steiner, N M Thielman, L Slutsker, R V Tauxe, T Hennessy, P M Griffin, H DuPont, R B Sack, P Tarr, M Neill, I Nachamkin, L B Reller, M T Osterholm, M L Bennish, L K Pickering, Infectious Diseases Society of America
Practice guidelines for the management of infectious diarrhea.
Clin Infect Dis. 2001 Feb 1;32(3):331-51. doi: 10.1086/318514. Epub 2001 Jan 30.
Abstract/Text
PMID 11170940
Emil C Reisinger, Carlos Fritzsche, Robert Krause, Guenter J Krejs
Diarrhea caused by primarily non-gastrointestinal infections.
Nat Clin Pract Gastroenterol Hepatol. 2005 May;2(5):216-22. doi: 10.1038/ncpgasthep0167.
Abstract/Text Infectious diseases that do not primarily affect the gastrointestinal tract can cause severe diarrhea. The pathogenesis of this kind of diarrhea includes cytokine action, intestinal inflammation, sequestration of red blood cells, apoptosis and increased permeability of endothelial cells in the gut microvasculature, and direct invasion of gut epithelial cells by various infectious agents. Of the travel-associated systemic infections presenting with fever, diarrhea occurs in patients with malaria, dengue fever and SARS. Diarrhea also occurs in patients with community-acquired pneumonia, when it is suggestive of legionellosis. Diarrhea can also occur in patients with systemic bacterial infections. In addition, although diarrhea is rare in patients with early Lyme borreliosis, the incidence is higher in those with other tick-borne infections, such as ehrlichiosis, tick-borne relapsing fever and Rocky Mountain spotted fever. Unfortunately, it is often not established whether diarrhea is an initial symptom or develops during the course of the disease. The real incidence of diarrhea in some infectious diseases must also be questioned because it could represent an adverse reaction to antibiotics.

PMID 16265204
Andi L Shane, Rajal K Mody, John A Crump, Phillip I Tarr, Theodore S Steiner, Karen Kotloff, Joanne M Langley, Christine Wanke, Cirle Alcantara Warren, Allen C Cheng, Joseph Cantey, Larry K Pickering
2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.
Clin Infect Dis. 2017 Nov 29;65(12):1963-1973. doi: 10.1093/cid/cix959.
Abstract/Text These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PMID 29194529
Nipam Shah, Herbert L DuPont, David J Ramsey
Global etiology of travelers' diarrhea: systematic review from 1973 to the present.
Am J Trop Med Hyg. 2009 Apr;80(4):609-14.
Abstract/Text Fifty-one published studies of travelers' diarrhea (TD) were examined to look for regional differences in pathogens identified. Enterotoxigenic E. coli was detected in 1,678/5,518 (30.4%) of TD cases overall, with rates in Latin America/Caribbean (L. America), Africa, south Asia, and Southeast Asia of 1,109/3,302 (33.6%), 389/1,217 (31.2%), 153/499 (30.6%), and 36/500 (7.2%), respectively (P < 0.001). Enteroaggregative E. coli was the second most common agent in L. America, found in 166/689 (24.1%), compared with 3/165 (1.8%) in Africa and 33/206 (16%) in south Asia (P < 0.001). Other significantly regional differences were seen for enteropathogenic E. coli, diffusely adherent E. coli, Campylobacter, Shigella spp., Salmonella, Aeromonas spp., Plesiomonas, Vibrios, rotavirus, noroviruses, Giardia, and Entoamoeba histolytica. The regional differences in pathogen identification identified will serve as a baseline for antimicrobial therapy recommendations and vaccines strategies.

PMID 19346386
G De Bruyn, S Hahn, A Borwick
Antibiotic treatment for travellers' diarrhoea.
Cochrane Database Syst Rev. 2000;(3):CD002242. doi: 10.1002/14651858.CD002242.
Abstract/Text BACKGROUND: Traveller's diarrhoea is a syndrome frequently encountered in persons crossing an international boundary. Diarrhoea can lead to significant discomfort and interference with travel plans. Bacterial pathogens are a frequent cause of this syndrome. Several antibiotics have been tested for efficacy in reducing the duration and severity of the illness.
OBJECTIVES: The aims of this review were to assess the effects of antibiotics on traveller's diarrhoea in relation to duration of illness, severity of illness, and adverse effects of medications.
SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted.
SELECTION CRITERIA: All trials in any language in which travellers older than 5 years were randomly allocated to treatment for acute non-bloody diarrhoea with antibiotics and where the causative organism is not known at allocation.
DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data.
MAIN RESULTS: Twenty published studies met inclusion and quality criteria for inclusion. Twelve studies were placebo-controlled. A meta-analysis for the primary outcome was not feasible. All of the 10 trials reported a significant reduction in duration of diarrhoea in participants treated with antibiotics compared with placebo. Data from two trials demonstrated a small reduction for antibiotic treated patients in the number of unformed stools passed per each 24 hour period from randomisation up to 72 hours. Data from six trials demonstrated a greater number of participants being cured of diarrhoea by 72 hours (odds ratio [OR] 5. 9, 95% confidence interval [CI] 4.06 to 8.57). Data regarding side effects were available from five trials. There was wide variation in the prevalence of side effects reported in different trials. Persons taking antibiotics experienced more side effects than those taking placebo (OR 2.37, 95% CI 1.5 to 3.75).
REVIEWER'S CONCLUSIONS: Antibiotic treatment is associated with shorter duration of diarrhoea but higher incidence of side-effects. Trials generally do not report duration of post-treatment diarrhoea using time-to-event analyses, and should do.

PMID 10908534
Mark S Riddle, Sarah Arnold, David R Tribble
Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in traveler's diarrhea: a systematic review and meta-analysis.
Clin Infect Dis. 2008 Oct 15;47(8):1007-14. doi: 10.1086/591703.
Abstract/Text BACKGROUND: A previous Cochrane Collaboration review established an effective advantage of antibiotic therapy, compared with placebo, for treatment of traveler's diarrhea. The goal of the present study was to conduct a systematic review of the literature to establish the effect on treatment outcomes of using antimotility agents in conjunction with antibiotic therapy.
METHODS: The meta-analysis was conducted through searches of electronic databases and pertinent reference lists (including other review articles) and consultation with experts in the field. Clinical trials on therapy of infectious diarrhea in adult populations that met eligibility criteria were studied. Data were extracted and verified by 2 independent investigators and were analyzed for outcomes of clinical cure at 24 h, 48 h, and 72 h and time to last unformed stool. Study quality, heterogeneity, and publication bias were assessed. When appropriate, effect estimates among studies were pooled and sensitivity analyses were performed.
RESULTS: Nine studies consisting of 12 different adjunctive loperamide antibiotic regimens were included for analysis. Among 6 paired studies comparing antibiotics alone versus antibiotics in combination with loperamide, the odds of clinical cure at 24 h and 48 h favored combination therapy, with summary odds ratios of 2.6 (95% confidence interval, 1.8-3.6; P = .20 by chi(2) heterogeneity statistic) and 2.2 (95% confidence interval, 1.5-3.1; P = .20, by chi(2) heterogeneity statistic), respectively, with no evidence of heterogeneity. Factors that possibly affect advantage of combination therapy over solo therapy included increased frequency of pretreatment diarrhea and higher prevalence of noninvasive pathogens.
CONCLUSION: Antibiotic therapy with adjunctive loperamide offers an advantage over antibiotics alone by decreasing the illness duration and increasing the probability of early clinical cure.

PMID 18781873
David R Tribble, John W Sanders, Lorrin W Pang, Carl Mason, Chittima Pitarangsi, Shahida Baqar, Adam Armstrong, Paul Hshieh, Anne Fox, Elisabeth A Maley, Carlos Lebron, Dennis J Faix, James V Lawler, Gautam Nayak, Michael Lewis, Ladaporn Bodhidatta, Daniel A Scott
Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen.
Clin Infect Dis. 2007 Feb 1;44(3):338-46. doi: 10.1086/510589. Epub 2006 Dec 28.
Abstract/Text BACKGROUND: Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed.
METHODS: Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication).
RESULTS: A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P=.03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%-100%), compared with levofloxacin (38%) (P=.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild, self-limited complaint associated with single-dose azithromycin.
CONCLUSIONS: Single-dose azithromycin is recommended for empirical therapy of traveler's diarrhea acquired in Thailand and is a reasonable first-line option for empirical management in general.

PMID 17205438
Joaquim Ruiz, Francesc Marco, Ines Oliveira, Jordi Vila, Joaquim Gascón
Trends in antimicrobial resistance in Campylobacter spp. causing traveler's diarrhea.
APMIS. 2007 Mar;115(3):218-24. doi: 10.1111/j.1600-0463.2007.apm_567.x.
Abstract/Text The aim of this study was to analyze the evolution of the levels of resistance to nine antimicrobial agents in clinical isolates of Campylobacter spp. causing traveler's diarrhea during the period from 1993 to 2003. The antimicrobial resistance levels to ampicillin, amoxicillin plus clavulanic acid, chloramphenicol, tetracycline, erythromycin, gentamicin, clindamicin, nalidixic acid and ciprofloxacin were established by the method of Kirby-Bauer. Two subperiods (1993-1998 and 1999-2003) were chosen to compare the evolution of the levels of antimicrobial resistance. Mantel-Haenszel or Fisher's exact test was performed to determine statistical significance. High levels of resistance to four out of nine antimicrobial agents tested were detected: ampicillin (66.3%), nalidixic acid (52.2%), ciprofloxacin (46.7%), and tetracycline (42.4%). In addition, resistance levels of 20.6% to amoxicillin plus clavulanic acid were detected. An increase in the resistance levels between the two subperiods analyzed for those five antimicrobial agents was observed. This increase was statistically significant for ampicillin, nalidixic acid, and ciprofloxacin. Two cases of therapeutic failure during treatment with ciprofloxacin were detected. The level of resistance to the most commonly used antibacterial agents in the developing world is increasing in Campylobacter spp., the increase in the resistance to quinolones being of special concern.

PMID 17367467
David R Hill, Charles D Ericsson, Richard D Pearson, Jay S Keystone, David O Freedman, Phyllis E Kozarsky, Herbert L DuPont, Frank J Bia, Philip R Fischer, Edward T Ryan, Infectious Diseases Society of America
The practice of travel medicine: guidelines by the Infectious Diseases Society of America.
Clin Infect Dis. 2006 Dec 15;43(12):1499-539. doi: 10.1086/508782. Epub 2006 Nov 8.
Abstract/Text
PMID 17109284

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