Review article: Rifaximin, a minimally absorbed oral antibacterial for the treatment of travellers’ diarrhoea Peter Layer, Viola Andresen
To cite this version:
Peter Layer, Viola Andresen. Review article: Rifaximin, a minimally absorbed oral antibacterial for the treatment of travellers’ diarrhoea. Alimentary Pharmacology and Therapeutics, Wiley, 2010, 31 (11), pp.1155. 10.1111/j.1365-2036.2010.04296.x. hal-00552547
HAL Id: hal-00552547 https://hal.archives-ouvertes.fr/hal-00552547 Submitted on 6 Jan 2011
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Review article: Rifaximin, a minimally absorbed oral antibacterial for the treatment of travellers' diarrhoea
ForJournal: Alimentary Peer Pharmacology Review & Therapeutics Manuscript ID: APT-0008-2010.R2
Manuscript Type: Review Article
Date Submitted by the 09-Mar-2010 Author:
Complete List of Authors: Layer, Peter; Israelitic Hospital Andresen, Viola; Israelitic Hospital
Diarrhoea < Topics, X keyword = no topic , Y keyword = no topic, Z Keywords: keyword = no topic
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C:\ScholarOne\conversions\7509596 1322205\$ASQ7509596_File000000_121344542.doc 1 2 3 Review article: Rifaximin, a minimally absorbed oral antibacterial for the 4 5 6 treatment of travellers’ diarrhoea 7 8 9 Peter Layer, MD, PhD; Viola Andresen, MD, MSc 10 11 12 Israelitic Hospital, Orchideenstieg 14, 22297 Hamburg, Germany 13 14 15 16 17 18 Address for correspondence: 19 20 For Peer Review 21 Peter Layer, MD, PhD 22 Professor of Medicine 23 Israelitic Hospital 24 Orchideenstieg 14 25 22297 Hamburg 26 Germany 27 Phone +49 40 51125 5001 28 Email: layer@ik h.de 29 30 31 32 33 Running title: Rifaximin in travellers’ diarrhoea 34 35 36 37 38 39 ACKNOWLEDGEMENTS 40 41 42 Medical writing support was provided by Euro RSCG Life Medicom and funded by Norgine. 43 44 45 Declaration of personal and funding interests 46 47 48 Professor Peter Layer has been a speaker and/or advisory board member for, and/or 49 50 recipient of unrestricted scientific grant by, the following pharmaceutical companies and 51 52 institutions: Abbott Laboratories, The Altana Group, Astra Zeneca, Axcan Pharma, Essex 53 54 55 Pharma, Falk Foundation, GlaxoSmithKline, Norgine, Novartis, Nycomed, Roche and 56 57 Solvay. 58 59 60 Dr Viola Andresen has been a speaker and/or advisory board member for Astra Zeneca,
Axcan Pharma, Falk Foundation, Norgine, Pfizer and Solvay.
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C:\ScholarOne\conversions\7509596 1322205\$ASQ7509596_File000000_121344542.doc 1 2 3 SUMMARY 4 5 6 Background 7 8 9 Travellers’ diarrhoea (TD), a common problem worldwide with significant medical impact, is 10 11 generally treated with anti diarrhoeal agents and fluid replacement. Systemic antibiotics are 12 13 also used in selected cases but these may be associated with adverse effects, bacterial 14 15 resistance and drug drug interactions. 16 17 Aim 18 19 To review the clinical evidence supporting the efficacy and safety of the minimally absorbed 20 For Peer Review 21 22 oral antibiotic rifaximin in TD. 23 24 Methods 25 26 PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and 27 28 International Society of Travel Medicine congress abstracts (2003 −2009) were searched to 29 30 identify relevant publications. 31 32 33 Results 34 35 A total of 10 publications were identified. When administered three times daily for 3 days, 36 37 rifaximin is superior to placebo or loperamide and at least as effective as ciprofloxacin in 38 39 reducing duration of illness and restoring wellbeing in patients with TD, both with and without 40 41 identification of a pathogen, as well as in Escherichia coli infection causing diarrhoea . 42 43 Rifaximin demonstrates only minimal potential for development of bacterial resistance and 44 45 46 for cytochrome P450 mediated drug drug interactions, and its tolerability profile is similar to 47 48 that of placebo. 49 50 Conclusions 51 52 When antibiotic therapy is warranted in uncomplicated TD, rifaximin may be considered as a 53 54 first line treatment option due to its favourable efficacy, tolerability and safety profiles. 55 56 57 58 59 Key words: antibiotic, enteropathogen, minimal absorption, rifaximin, travellers’ diarrhoea 60
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C:\ScholarOne\conversions\7509596 1322205\$ASQ7509596_File000000_121344542.doc 1 2 3 BACKGROUND 4 5 6 Travellers’ diarrhoea (TD) is a clinical syndrome frequently encountered by individuals (e.g. 7 8 9 holidaymakers, business travellers, military personnel) visiting certain regions of the world, 10 11 particularly the Middle East, Southern Asia, South and Central America, and the developing 12 13 nations of Africa. 1 The incidence of TD varies between specific locations, ranging between 14 15 20% and 90% for these regions, and is calculated to affect 15 −20 million travellers each year 16 17 worldwide. 2−4 18 19 20 For Peer Review 21 TD is characterized by acute diarrhoea, often accompanied by nausea, vomiting, abdominal 22 23 cramps and fever, due to the translocation of fluid and salts from the vascular to the mucosal 24 25 side of the gut, where they are lost. The impact of TD involves not only significant morbidity, 26 27 but also interruption to plans and daily activities. 1−3, 5, 6 In the majority of cases, symptoms 28 29 last 3 −4 days; 2, 3 however, in some instances, affected individuals may experience persistent 30
31 7 32 diarrhoea lasting for more than 2 weeks. In addition, more than 10% of people experiencing 33 8 34 TD may go on to develop post infectious irritable bowel syndrome (PI IBS). The primary 35 36 causative agents of TD are pathogenic enteric bacteria, most commonly enterotoxigenic 37 38 Escherichia coli (ETEC), enteroaggregative Escherichia coli (EAEC), Campylobacter jejuni , 39 40 Salmonella species and Shigella species. 9−12 However, prevalence of the bacteria causing 41 42 43 TD differs between geographical locations and up to 40% of TD cases are of unknown 44 6, 10, 13 45 aetiology, even after comprehensive microbiological evaluation. 46 47 48 Following anti diarrhoeal agents and fluid replacement, treatment of TD includes empiric 49 50 broad spectrum oral antibiotic therapy. The goal of treatment is to achieve a rapid resolution 51 52 of diarrhoea, in order to minimize disruption to planned activities, with only a short course of 53 54 treatment, and to minimize person to person spread of TD. 9, 14 A systematic review of clinical 55 56 57 studies (completed up to the year 2000) has concluded that antibiotic therapy for TD is 58 59 associated with a reduction in frequency of unformed stools passed at 24 hour intervals (i.e. 60 severity) and a significantly increased likelihood (around six fold) of achieving resolution of
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C:\ScholarOne\conversions\7509596 1322205\$ASQ7509596_File000000_121344542.doc 1 2 3 diarrhoea and other symptoms (clinical cure) within 72 hours of treatment initiation, versus 4 5 15 6 no treatment (placebo). However, there are differences in efficacy between antibiotic
7 11 8 agents. 9 10 11 In addition to broad spectrum activity against a range of bacterial enteropathogens and 12 13 efficacy against the symptoms of TD, other factors should be considered when selecting an 14 15 appropriate antibacterial treatment. These include specific targeted activity at the infection 16 17 site/poor systemic absorption,16 plus a low potential for side effects, 10, 15 drug interactions 1 18 19 and development of antibacterial resistance. 9 20 For Peer Review 21 22 Many antibacterials, such as the fluoroquinolones, are well absorbed into the systemic 23 24 17, 18 25 circulation after oral administration. This may be associated with an increased risk of 26 27 systemic adverse effects, most commonly dizziness and headache, and more rarely, hepatic 28 29 dysfunction or psychiatric adverse effects. 18 −21 In addition, resistance to fluoroquinolone 30 31 antibacterials among many of the pathogenic bacteria causing TD, such as ETEC, C. jejuni , 32 33 Shigella species and Salmonella species has been reported in many countries around the 34
35 22 −26 36 world, thus limiting their utility. Resistance of faecal E. coli and Shigella isolates from 37 38 subjects with TD to other (older) antibacterials, such as trimethoprim