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Diarrhoea - prevention and advice for travellers - Management
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Overview of management

  • Assess the risk of traveller's diarrhoea.
    • The risk is highest for people travelling to the Middle East, Africa, Central and South America, and most of Asia.
  • For people at low or intermediate risk of traveller's diarrhoea:
    • Provide information on food hygiene and safe drinking water if the person is travelling to locations with low standards of hygiene and sanitation.
    • Offer advice regarding self-management and when to seek medical advice if they develop diarrhoea during their travels.
  • For people at high risk of traveller's diarrhoea:
    • Emphasize the importance of personal hygiene, as well as food hygiene and safe drinking water, to reduce the risk of traveller's diarrhoea.
    • Warn the person about the risk of waterborne infection and to avoid contaminated recreational water.
    • Do not routinely offer prophylactic antibiotics for prevention of traveller's diarrhoea.
      • Antibiotic prophylaxis may be appropriate for certain high-risk travellers.
      • Consider whether a prescription for empirical antibiotic treatment to use if affected is a more suitable alternative if prophylaxis is not indicated, and the person is travelling to particularly high-risk locations where medical assistance is poor or not available.
      • For information on the choice of antibiotic, see How to prescribe antibiotics.
    • Inform the person that there are no universal vaccines for traveller's diarrhoea. However, travellers to risky areas must seek advice about appropriate vaccination against other intestinal infections such as cholera, hepatitis A, and typhoid. For further information on vaccines recommended for overseas travel, and extended holidays or for people working overseas, see the CKS topic on Immunizations - travel.
    • Offer advice regarding self-management and when to seek medical advice if the person develops diarrhoea during their trip.

How should I assess the risk of someone developing traveller's diarrhoea?

  • Enquire about the country to be visited.
    • Countries and places with generally poor standards of hygiene pose a greater risk.
      • Although the risks are greater in developing countries, locations with poor hygiene may be present in any country.
    • In general, the relative risk of traveller's diarrhoea can be classed as:
      • Low for people travelling to northern and western European countries, the USA and Canada, Japan, Australia, and New Zealand.
      • Intermediate for people travelling to eastern European countries, Russia, South Africa, and some of the Caribbean islands.
      • High for people travelling to the Middle East, Africa, Central and South America, and most of Asia.
    • For assessment of individual countries where travellers should practice strict food, water, and personal hygiene precautions, see the National Travel Health Network and Centre (NaTHNaC) website (www.nathnac.org).
  • Assess for other risk factors known to further increase the risk of traveller's diarrhoea, such as poor accommodation and sanitation amenities — see Additional information.
  • Review the person's susceptibility to traveller's diarrhoea and their risk of complications. Those at higher risk include:
    • Young children and babies, and elderly or frail people.
    • People with reduced immunity (such as those with HIV infection or AIDS).
    • People with severe cardiac or renal disease.
    • People with inflammatory bowel disease.
    • People with reduced acidity in the stomach, which is a risk factor for infection with acid-sensitive organisms such as Salmonella and Campylobacter.
  • Enquire about access to medical amenities — this is particularly important for those travelling to remote areas with few or no medical amenities (especially trekking, camping).
  • Discuss whether journeys to high-risk areas are essential and whether the person is suitably prepared (for example if backpacking through remote areas).
    • Some people may have been inadequately informed or prepared of the risks of a holiday in a high-risk area and may wish to travel to a lower risk area instead.
Additional information

The risk for traveller's diarrhoea depends on:

  • The country being visited — countries and places with generally poor standards of hygiene pose a greater risk.
  • Local amenities and sanitation — for example in areas with poor sewage facilities or access to safe drinking water, there is a high risk of contamination and poor sanitation.
  • How the person will be travelling — trekkers, campers, adventurers, and passengers on cruise ships are at increased risk.
  • When the person will be travelling — the peak incidence of traveller's diarrhoea is in the summer. In South Asia, a higher rate of traveller's diarrhoea is reported during the hot months preceding the monsoon season.
  • What the person eats — for example shellfish and other filter feeders (including mussels, oysters, and clams) tend to concentrate viral and bacterial pathogens and toxins.
  • The person's susceptibility to illness — for example reduced acidity in the stomach is a risk factor for infection with acid-sensitive organisms such as Salmonella and Campylobacter [Neal et al, 1996].

[Ericsson, 2003; Al-Abri et al, 2005; CDC, 2009]

Basis for recommendation

These recommendations are based on published US guidelines and expert opinion [Al-Abri et al, 2005; CDC, 2009; Dupont, 2009; Shah et al, 2009].

Risk of traveller's diarrhoea

  • The travel destination is regarded as the most important determinant of risk [CDC, 2009; Dupont, 2009].
    • The risk of traveller's diarrhoea is highest for people from developed countries travelling to developing countries, with 30–50% of travellers estimated to develop traveller's diarrhoea during a 1–2 week stay.
    • For people travelling to countries with intermediate risk (for example Asia and Russia), the rate is 8–15%.
    • The rate is lowest (less than 4%) for people travelling between two low-risk regions (for example between the USA and western Europe).

How should I advise someone at low or intermediate risk of traveller's diarrhoea?

For people at low or intermediate risk of traveller's diarrhoea:

  • Reassure the person that no special precautions (other than basic hygiene measures) are required when travelling to locations with a high standard of hygiene.
  • Provide information on food hygiene and safe drinking water if the person is travelling to locations with low standards of hygiene and sanitation.
  • Offer advice regarding self-management and when to seek medical advice if the person develops diarrhoea during their trip.
Basis for recommendation

How should I manage someone at high risk of traveller's diarrhoea?

For people at high risk of traveller's diarrhoea:

  • Emphasize the importance of personal hygiene, as well as food hygiene and safe drinking water, to reduce the risk of traveller's diarrhoea.
  • Warn travellers about the risk of food- and water-borne infections and how to avoid potentially contaminated recreational water.
  • Do not routinely offer prophylactic treatment for prevention of traveller's diarrhoea, as it is not indicated for most travellers.
    • Antibiotic prophylaxis may be appropriate for certain high-risk travellers (see Prophylactic or empirical antibiotics).
    • The use of bismuth subsalicylate and probiotics for prophylaxis is not recommended.
    • Antidiarrhoeal drugs (such as loperamide) should not be taken prophylactically.
  • Consider whether a prescription for empirical antibiotic treatment (to use if affected) is a suitable alternative if prophylaxis is not indicated, and the person is travelling to particularly high-risk locations where medical assistance is poor or unavailable (see Prophylactic or empirical antibiotics).
  • Inform the person that there are no universal vaccines to cover all the infections which may cause traveller's diarrhoea. However, travellers to risky areas must seek advice about appropriate vaccination against other intestinal infections such as cholera, hepatitis A, and typhoid. For further information on vaccines recommended for overseas travel, and extended holidays or for people working overseas, see the CKS topic on Immunizations - travel.
  • Offer advice regarding self-management and when to seek medical advice if the person develops diarrhoea during their trip.
Basis for recommendation

Food hygiene and safe drinking water

Prophylactic treatments

  • Apart from the use of prophylactic antibiotics for certain at-risk groups (see Prophylactic or empirical antibiotics), WHO does not recommended any particular measures for the prophylaxis of traveller's diarrhoea [WHO, 2009]. WHO warns that antidiarrhoeal medicines such as loperamide are contraindicated for prophylactic use.

Probiotics

  • Probiotics are not recommended for the prevention of traveller's diarrhoea because CKS found insufficient evidence to support their use.

Bismuth subsalicylate (Pepto-Bismol®)

  • The use of bismuth subsalicylate (off-label indication) for prophylaxis for traveller's diarrhoea is not recommended because:
    • Although it was up to 60% more effective than placebo in reducing the incidence of traveller's diarrhoea, this was based on limited evidence from three small trials.
    • Antibiotics are a more effective option and are estimated to be around 80% effective (provided they have activity against the enteropathogens in that geographical region) [Ericsson, 2003].
  • The usefulness of bismuth treatment may be limited by the following:
    • Compliance may be difficult as the treatment (30 mL or two tablets) needs to be taken four times a day.
    • Prophylaxis is recommended for up to 3 weeks (based on duration of trials) and the quantity required might be inconvenient to carry.
    • Adverse effects are common (particularly black tongue and stool) and the risk of tinnitus is of concern.
    • The salicylate content is high: one day's treatment is equivalent to taking four 325 mg aspirin tablets daily [Thomas, 2000; Ericsson, 2005]. Consequently, it is not suitable for people with aspirin allergy, renal insufficiency, gout, or those taking anticoagulants [Hill and Ryan, 2008; CDC, 2009], as well as those with a history of peptic ulcer disease or at increased risk of gastrointestinal bleeding.
    • Pepto-bismol® is not licensed for children younger than 16 years of age due to a possible association between salicylates and Reye's syndrome [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2009b].

Vaccination

  • A universal vaccine to protect against the general syndrome of traveller's diarrhoea is not possible due to the wide range of possible causes.
  • An oral cholera vaccine (Dukoral®) may produce cross-protective immunity against enterotoxigenic Escherichia coli (which expresses a heat labile enterotoxin similar to cholera toxin). However, the effectiveness of this vaccine is limited, because [Hill et al, 2006; Hill and Ryan, 2008]:
    • Up to 50% of enterotoxigenic E. coli strains do not express this particular heat labile enterotoxin.
    • Protection is variable. It is estimated that the vaccine will only prevent 1–7% of cases of traveller's diarrhoea, depending on the destination and prevalence of enterotoxigenic E. coli strains which produce this heat labile enterotoxin.

What food and drink measures are recommended for preventing traveller's diarrhoea?

General hygiene

  • Hands should always be washed before handling and consuming food — particularly after contact with raw meat and uncooked food.

Advice on food and drink

  • Food must have been thoroughly cooked, and must remain steaming hot prior to serving.
    • Raw seafood should be avoided, as well as any meat or poultry that has not been thoroughly cooked.
    • Food from buffets, markets, restaurants, and street vendors should be avoided, if this has not either been kept hot, or refrigerated or kept on ice.
    • Cooked food that has been in contact with raw food, or contains raw or uncooked eggs (such as homemade mayonnaise), should be avoided.
  • Fruits and vegetables that can be peeled or shelled are suitable choices.
    • Fruits and vegetables with damaged skins should be avoided.
  • Ice should be avoided, unless it has been made from safe water.
  • Ice-cream from unreliable sources, including street vendors, should be avoided.
  • Unpasteurized (raw) milk should be boiled before consumption.
  • Carbonated bottled beverages are usually safe to drink provided they are sealed, as they are normally free from microorganisms which could cause traveller's diarrhoea.

Advice on drinking water

  • Bottled water is the safer choice for drinking water. The seal must not have been tampered with.
  • Water should be boiled (for at least 1 minute) if its safety for drinking is in doubt.
  • Other options include micropore filtering and the use of disinfectant preparations. These might be more relevant for people travelling to areas where there is little or no access to safe drinking water.
  • Advise the use of oral rehydration salt solution for the management and prevention of dehydration (particularly for children and infants). For further information, see Advice on traveller's diarrhoea.

Information leaflets on preventing food disease (pdf) and on ensuring safe drinking water (pdf) are available on the World Health Organization website (www.who.int).

Basis for recommendation

These recommendations are based on guidance issued by the World Health Organization (WHO) [WHO, 2005; WHO, 2007; WHO, 2009].

When should I consider prescribing prophylactic or empirical antibiotic for traveller's diarrhoea?

  • Antibiotics should not routinely be prescribed for the prevention or empirical (if required) treatment of traveller's diarrhoea.
  • Consider prophylactic antibiotics only for people who are at high risk of traveller's diarrhoea and who:
    • Have increased susceptibility to infection or are immunocompromised, for example:
      • People receiving chemotherapy or immunosuppressive drugs.
      • People with HIV infection.
    • Have a high risk of complications if they were to develop traveller's diarrhoea, for example:
      • People with chronic gastrointestinal disease (such as Crohn's disease, ulcerative colitis).
      • People with an ileostomy or colostomy.
      • People with other chronic diseases (such as Type 1 diabetes mellitus, renal disease, congestive heart failure) in whom a diarrhoeal illness might severely impact on their health.
    • Are undertaking critical trips in which a short bout of diarrhoea could severely impact the purpose of the trip.
    • Note: for people taking acid-suppressive drugs (such as proton pump inhibitors), antibiotic prophylaxis should not be routinely offered unless they have a high risk of complications (for example, if they are immunocompromised).
  • Consider empirical antibiotics for people who:
    • Are travelling to high-risk locations where access to medical assistance is poor or not available and antibiotic prophylaxis is not the preferred choice.
  • For information on how to prescribe prophylactic or empirical antibiotics, see How to prescribe antibiotics.
Additional information
  • The decision to prescribe an antibiotic depends on an assessment of:
    • The risk of the person developing traveller's diarrhoea (see Assessing risk).
    • The potential harm to the person if they were to develop traveller's diarrhoea.
    • The benefits and risks of antibiotic treatment.
    • Access to medical assistance while travelling.
Basis for recommendation

Antibiotic prophylaxis

  • There is evidence that prophylactic antibiotics are effective in preventing traveller's diarrhoea, given that bacterial infection is a major cause of this condition.
  • However, the World Health Organization (WHO) warns that the use of prophylactic antibiotics is controversial (with some experts not recommending this [NIH Consensus Development Program, 1985; Thielman and Guerrant, 2004]), although WHO acknowledges that there is a role for their use in travellers with increased susceptibility to infection and for those individuals on critical missions [WHO, 2009].
  • This is supported by US guidelines [Hill et al, 2006; CDC, 2009] which also recommend that antibiotic prophylaxis should not be routinely prescribed because:
    • Antibiotic prophylaxis offers no protection against non-bacterial causes of traveller's diarrhoea (such as viruses and parasites).
    • For most people, traveller's diarrhoea is mild and self-limiting.
    • Self-treatment with a short course of antibiotics (up to 3 days) can reduce the duration of traveller's diarrhoea.
    • Taking antibiotic prophylaxis may give the traveller a false sense of security, which might lead to neglect of food and water precautions.
    • The increasing prevalence of antibiotic resistance is of concern (including to fluoroquinolones [Hakanen et al, 2003; Ruiz et al, 2007; Vlieghe et al, 2008]).
    • Antibiotic treatment can lead to adverse effects.
      • Reports of Clostridium difficile infection (which can be potentially life-threatening) have been reported for people taking antibiotics for the treatment of traveller's diarrhoea [Norman et al, 2008]. The risk of C. difficile infection is increased in people taking a longer course of antibiotics (such as for prophylaxis).
      • Other adverse effects associated with antibiotics include gastrointestinal symptoms (such as diarrhoea), allergic reactions, vaginal thrush, and sun sensitivity (associated with quinolones).
  • There is no evidence to support the effectiveness of antibiotic prophylaxis for people travelling to countries with low or intermediate risk of traveller's diarrhoea.
    • One double-blind trial in 127 participants found antibiotic treatment (norfloxacin) to be effective in reducing the number of Swedish travellers developing diarrhoea in high-risk countries (Africa, Asia, or Latin America, p = 0.0004) but not for those travelling to low-risk countries (Mediterranean Europe or the Canary Islands) [Wiström et al, 1987].
  • No antibiotics are licensed in the UK for the prophylaxis of traveller's diarrhoea.

Groups considered for antibiotic prophylaxis

People on acid-suppressive therapy

  • Although people on acid-suppressive therapy (such as proton pump inhibitors) are at increased risk of traveller's diarrhoea, the majority of CKS expert reviewers recommend that antibiotic prophylaxis should not be offered routinely to this group unless they have a high risk of complications (for example, if they are immunocompromised).

Empirical antibiotics for treatment of traveller's diarrhoea

  • There is evidence from a Cochrane systematic review supporting the use of antibiotics for treating traveller's diarrhoea [de Bruyn et al, 2000]. Secondary outcomes indicate that antibiotics are more effective than placebo at increasing the number of people cured after 72 hours and at reducing the severity of diarrhoea. However, antibiotic treatment was associated with more adverse effects than placebo.
  • Antibiotic treatment usually limits the duration of illness by an average of about 1 day (for further information, see the evidence on Antibiotic treatment) [WHO, 2009].

Indication for empirical antibiotic treatment

  • The recommendation to offer empirical treatment to people travelling to high-risk regions where medical assistance is poor or limited is in line with the recommendation from WHO. WHO recommends that antibiotic treatment should be used where there is no medical help available and if bowel movements become 'very frequent, very watery or contain blood, or last beyond 3 days' [WHO, 2007].

How should I prescribe antibiotics for prophylaxis or empirical treatment of traveller's diarrhoea?

  • For the prophylaxis of traveller's diarrhoea:
    • Prescribe ciprofloxacin 500 mg once daily (off-label use, requiring private prescription) for up to 3 weeks.
    • Do not prescribe ciprofloxacin for the following groups; seek specialist advice:
      • Children and adolescents.
      • Women who are pregnant or breastfeeding.
      • People travelling to countries where quinolone resistance is prevalent (for example Thailand and the Far East).
      • People for whom quinolones are not suitable or contraindicated.
    • Azithromycin is not suitable for prophylaxis.
  • For the empirical treatment of traveller's diarrhoea (to be taken if needed):
    • Prescribe ciprofloxacin 500 mg twice daily for 3 days (licensed indication, requiring private prescription).
      • Advise the person to evaluate response after 24 hours of taking antibiotic (see advice below).
    • Prescribe azithromycin (off-label use, requiring private prescription) instead of ciprofloxacin for the following groups:
      • Children and adolescents.
      • People travelling to countries where quinolone resistance is prevalent (for example Thailand and the Far East).
      • Pregnant women.
      • People for whom quinolones are contraindicated.
    • For adults and children of more than 45 kg body weight, prescribe azithromycin 500 mg daily for 3 days (off-label use).
    • For children 6 months of age or more who weigh less than 45 kg, prescribe azithromycin 10 mg/kg once daily (maximum dose 500 mg once daily) for 3 days (off-label use). As a guide:
      • Body weight 15–25 kg (approximately 3–7 years of age): 200 mg once daily for 3 days.
      • Body weight 26–35 kg (8–11 years of age): 300 mg once daily for 3 days.
      • Body weight 36–45 kg (12–14 years of age): 400 mg once daily for 3 days.
      • Body weight greater than 45 kg: dose as for adults.
      • Remind the parent or carer that azithromycin 200 mg/5 mL suspension must be reconstituted using safe drinking water.
    • Advise on the appropriate use of empirical antibiotics:
      • Antibiotics should be taken only when symptoms are moderate-to-severe (for example bowel movements becoming very frequent, very watery, or containing blood) or if symptoms last beyond 3 days.
      • The person should assess their response to treatment after 24 hours — if they are still unwell they should complete the 3-day course, but if they are much improved there is no need to continue treatment.
      • The addition of loperamide (off-label use) can be considered if immediate control of symptoms is required, but loperamide must be avoided if the person is feverish or has bloody diarrhoea. The combination should not be used for more than 2 days.
Prescribing information

Ciprofloxacin

  • Contraindications and precautions
    • Ciprofloxacin should not be used in people with a history of tendon disease/disorder related to quinolone treatment, or who are taking tizanidine or methotrexate.
    • Ciprofloxacin should be used with caution in people with central nervous system disorders who may be predisposed to seizure [CSM, 1991].
    • Because of the possible risk of arthropathy, ciprofloxacin should not routinely be prescribed to children and adolescents. Other quinolones are not licensed for use in these age groups.
  • Pregnancy and breastfeeding
    • Because of the risk of arthropathy in the fetus and infant, all manufacturers of quinolones recommend that these antibiotics should be avoided in women who are pregnant or breastfeeding. Seek specialist advice before prescribing quinolones in these women.
  • Advise the person to stop taking ciprofloxacin if they develop any of the following:
    • Tendinitis or tendon rupture (especially of the Achilles tendon): this can be bilateral and occur as soon as within the first 48 hours of treatment [CSM, 2002]. The risk of tendonopathy may be increased in elderly people and in people who are also taking corticosteroids.
    • Convulsions: quinolones such as ciprofloxacin are known to trigger seizures or lower the seizure threshold. Ciprofloxacin should be used with caution in people with central nervous system disorders which may predispose them to seizure.
    • Polyneuropathy; neurological symptoms such as pain, burning, sensory disturbances, or muscle weakness, alone or in combination.
  • Inform the person that:
    • Ciprofloxacin has been shown to cause photosensitivity reactions. People taking ciprofloxacin should avoid direct exposure to extensive sunlight or ultraviolet irradiation during treatment.

Azithromycin

  • Contraindications
    • The manufacturer of azithromycin recommends that people prescribed ergot derivatives (such as ergotamine — not commonly prescribed) should avoid azithromycin because of the theoretical possibility of ergotism.
  • Pregnancy
    • Azithromycin is recommended as the first-line antibiotic by WHO for treating traveller's diarrhoea in pregnant women [WHO, 2009].
  • Breastfeeding
    • Information is limited on the excretion of azithromycin in breast milk.
    • Although not contraindicated, the manufacturer advises that the decision to prescribe azithromycin should be based on an assessment of benefits and harms to the mother and fetus.
    • Azithromycin is regarded as a second-line macrolide for use in women who are breastfeeding [Schaefer et al, 2007].

[ABPI Medicines Compendium, 2008b; ABPI Medicines Compendium, 2008c]

Basis for recommendation

Antibiotic choice for the prophylaxis and empirical treatment of traveller's diarrhoea

  • Fluoroquinolones are generally recommended for adults (except for pregnant or breastfeeding women and people travelling to locations with widespread quinolone resistance) due to the resistance of micro-organisms to other antibiotics [Hill et al, 2006; CDC, 2009].
  • In countries where quinolone resistance is unknown, the use of quinolones (such as ciprofloxacin) is supported by the majority of CKS expert reviewers.
  • Although other fluoroquinolones may be offered, ciprofloxacin is preferred because:
    • It is less expensive than other fluoroquinolones and there is evidence to support its use for the prophylaxis and treatment of traveller's diarrhoea.
    • Unlike other fluoroquinolones, ciprofloxacin is licensed for the treatment of gastrointestinal tract infection, including the empirical treatment of severe traveller's diarrhoea [ABPI Medicines Compendium, 2008c].
  • Although rifaximin (a poorly absorbed antibiotic) is also recommended in some sources, it is not available in the UK.
  • Doxycycline, taken for malaria prophylaxis, offers little or no protection against traveller's diarrhoea in most areas of the world.

Azithromycin as an alternative to ciprofloxacin for empirical treatment

  • Although it is not licensed for the treatment of traveller's diarrhoea, azithromycin is recommended by the World Health Organization (WHO), and by experts, for the treatment of traveller's diarrhoea if resistance to fluoroquinolones is suspected or known [Al-Abri et al, 2005; Hill et al, 2006; WHO, 2009].
  • It is also recommended as the first-line antibiotic by WHO, and by experts, for treating traveller's diarrhoea in children and pregnant women [Hill and Ryan, 2008; WHO, 2009].
    • Ciprofloxacin and other quinolones should be avoided in children and adolescents, and in pregnant or breastfeeding women because of the increased risk of quinolone-associated arthropathy in the child or fetus [ABPI Medicines Compendium, 2008c].
    • The manufacturer of ciprofloxacin recommends that ciprofloxacin treatment should be initiated in children only 'by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents' [ABPI Medicines Compendium, 2008c].
    • Manufacturers of other quinolones warn that these antibiotics are contraindicated in children and growing adolescents [ABPI Medicines Compendium, 2009c; ABPI Medicines Compendium, 2009d; ABPI Medicines Compendium, 2009e].
    • All the manufacturers of quinolones state they should not be used in pregnant or breastfeeding women.
  • The off-label dosages provided are extrapolated from those recommended by the manufacturer of azithromycin [ABPI Medicines Compendium, 2008b].

Antibiotics that are not recommended for prophylaxis and empirical treatment

  • Co-trimoxazole, doxycycline, and trimethoprim are no longer considered effective against the enteric bacterial pathogens involved in traveller's diarrhoea, due to widespread resistance in most areas of the world [Al-Abri et al, 2005; CDC, 2009].

Duration of antibiotic prophylaxis

Duration of empirical treatment

Antibiotic prophylaxis for children and adolescents, and women who are pregnant or breastfeeding

  • CKS recommends seeking specialist advice because there are no data supporting antibiotic prophylaxis for these groups [Hill et al, 2006].
  • In addition quinolones should be avoided in these people because of the increased risk of quinolone-associated arthropathy in the child or fetus [ABPI Medicines Compendium, 2008c].
  • Although azithromycin is recommended as an alternative to quinolones for treating traveller's diarrhoea, no studies have been undertaken to determine an appropriate dose for azithromycin prophylaxis [Al-Abri et al, 2005; Hill et al, 2006].

Antibiotic prophylaxis for regions where quinolone resistance is widespread

  • CKS recommends seeking specialist advice if the person is planning to travel to regions where resistance to fluoroquinolones is high (predominantly Campylobacter species), such as India, Thailand, and the Far East, because:
    • There is currently no other antibiotic with demonstrated prophylactic efficacy against Campylobacter species [Hill et al, 2006; Hill and Ryan, 2008].
    • No studies have been undertaken using azithromycin for prophylaxis.

Combination of antibiotic and loperamide

  • The combination of an antibiotic and loperamide has been recommended to reduce the frequency of bowel movement for people who need immediate control of symptoms [Hill and Ryan, 2008; CDC, 2009; WHO, 2009].
  • There is limited evidence from a systematic review that a combination of loperamide and antibiotic treatment is more effective than antibiotic alone in treating traveller's diarrhoea [Riddle et al, 2008]. More people were cured after 24 hours and 48 hours, but not after 72 hours, of starting treatment. However, in terms of the time to the last diarrhoeal stool for the two treatments, the differences were variable, ranging from 2–22 hours. This result should be interpreted with caution given the significant heterogeneity of the studies.
  • The combined use of loperamide and antibiotics in the presence of fever or blood in the stool is controversial [Ericsson, 2003]. Some experts recommend this combination should only be used when there is no fever or blood in the stool [Hill et al, 2006; Hill and Ryan, 2008]. For people with fever or blood in the stool, there are concerns that loperamide can inhibit peristalsis, resulting in complications such ileus, megacolon, and toxic megacolon.
  • Given that the above systematic review failed to assess adverse effects (people with fever or blood in the stool were excluded from the trials) and the limited evidence supporting its use, CKS advises that the combination should be avoided when there is fever or blood in the stool.

What should I advise about managing traveller's diarrhoea while travelling?

  • Advise the person that most episodes of traveller's diarrhoea are mild and self-limiting, lasting around 3–5 days.
  • The person could consider purchasing sachets of oral rehydration salt before travelling — particularly for infants.
  • During an episode of diarrhoea, fluid intake should be increased to prevent dehydration — this is particularly important for infants, young children, and elderly people.
    • For infants, breastfeeding should not be interrupted.
    • Hydration must be maintained, for example with oral rehydration salt solution and boiled, treated, or bottled water.
    • Safe drinking water should be used to reconstitute oral rehydration salt sachets.
    • Alcohol and other drinks and beverages with a diuretic effect (such as coffee and tea) should be avoided.
    • Immediate medical attention is required if children show signs of dehydration; such as restlessness or irritability, great thirst, sunken eyes, and dry skin with reduced elasticity.
  • Neither loperamide nor Pepto-Bismol® are recommended for children to relieve diarrhoeal symptoms.
    • Loperamide should not be used in children younger than 12 years of age because of concerns that it may cause intestinal obstruction.
    • Pepto-Bismol® contains salicylate and must not be used in children younger than 16 years of age because of the possible association between salicylates and Reye's syndrome.
  • Both loperamide and Pepto-Bismol® may be considered in adults for relieving mild-to-moderate diarrhoea.
    • They should be used for no longer than 1–2 days.
    • Loperamide can be considered when rapid control of symptoms is required — for example during travelling where toilet amenities are limited or unavailable.
    • Because of its salicylate content, Pepto-Bismol® is not suitable for people with aspirin allergy, renal insufficiency, gout, or who are taking an anticoagulant such as warfarin, as well as those at risk of gastrointestinal bleeding. Darkened tongue and stools are common adverse effects.
    • Loperamide should be avoided if the person is feverish, or has bloody diarrhoea or acute ulcerative colitis, as it can inhibit peristalsis, resulting in complications such ileus, megacolon, and toxic megacolon.
  • Certain medications may be affected by severe diarrhoea (for example the effectiveness of warfarin, anticonvulsants, and the oral contraceptive pill are reduced) or can exacerbate dehydration (for example diuretics).
  • Medical assistance must be sought if:
    • Stools are blood stained, or there is fever.
    • The person becomes dehydrated — particularly in infants and children (restlessness or irritability, very thirsty, sunken eyes, and dry skin with reduced elasticity).
    • It is difficult to maintain adequate hydration, because of frequent, watery stools, or repeated vomiting.
    • Diarrhoea persists for more than 3 or 4 days.
    • Diarrhoea does not respond within 3 days to empirical antibiotic treatment.
  • Advice for travellers can be found on the following websites:
Basis for recommendation

Measures to prevent dehydration

  • These recommendations are based on guidelines issued by the World Health Organization (WHO) on managing traveller's diarrhoea [WHO, 2007; WHO, 2009].

Symptomatic treatment for children is not recommended.

  • CKS found no evidence to support the use of bismuth subsalicylate and loperamide in children with traveller's diarrhoea.
  • The recommendation to avoid loperamide in children younger than 13 years of age is in line with guidance from WHO, which advises against the use of loperamide and other antimotility drugs because they may cause intestinal obstruction [WHO, 2007]. Over-the-counter loperamide is only licensed for use in children older than 12 years of age [ABPI Medicines Compendium, 2008].
  • Bismuth salicylate (Pepto-Bismol®) is not licensed for use in children younger than 16 years of age because of the possible association between salicylates and Reye's syndrome [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2009b].

Symptomatic treatment for adults

  • Symptomatic treatment is usually not necessary because traveller's diarrhoea is generally a mild, self-limiting illness.
    • CKS found limited evidence to support the use of bismuth subsalicylate and loperamide for traveller's diarrhoea in adults. Trials were generally of poor methodological quality. Although a reduction in stool frequency was reported when compared with placebo, the differences were small.
    • Some experts recommended their use for mild-to-moderate traveller's diarrhoea [Ericsson, 2003; Hill and Ryan, 2008].
  • Comparison between loperamide and bismuth subsalicylate
    • There is weak evidence from two unblinded trials in students with traveller's diarrhoea that loperamide is more effective than bismuth subsalicylate at reducing the number of unformed stools in the initial stage of treatment (generally within the first 24 hours). However, the differences were small and the clinical significance is uncertain.
    • Consequently, loperamide (widely available over-the-counter) might be considered when rapid control of symptoms is required — for example during travelling where toilet amenities are limited or unavailable.
    • This is in line with expert opinion [Ericsson, 2003; Hill et al, 2006; DuPont et al, 2009a].
  • Recommended indications and precautions for loperamide and bismuth subsalicylate (Pepto-Bismol®)

When to seek medical assistance

Prescriptions

For information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

Prophylactic ciprofloxacin: adults (except pregnant/breastfeeding women)

Age from 18 years onwards
Ciprofloxacin tablets: 500mg daily (1 week)
Ciprofloxacin 500mg tablets
Take one tablet once a day.
Supply 7 tablets.
Age: from 18 years onwards
Licensed use: no - off-label indication
Private prescription: yes
Ciprofloxacin tablets: 500mg daily (2 weeks)
Ciprofloxacin 500mg tablets
Take one tablet once a day.
Supply 14 tablets.
Age: from 18 years onwards
Licensed use: no - off-label indication
Private prescription: yes
Ciprofloxacin tablets: 500mg daily (3 weeks)
Ciprofloxacin 500mg tablets
Take one tablet once a day.
Supply 21 tablets.
Age: from 18 years onwards
Licensed use: no - off-label indication
Private prescription: yes

Empirical ciprofloxacin: adults (except pregnant/breastfeeding women)

Age from 18 years onwards
Ciprofloxacin tabs: 500mg twice a day for 3 days
Ciprofloxacin 500mg tablets
Take one tablet twice a day for 3 days.
Supply 6 tablets.
Age: from 18 years onwards
Licensed use: yes
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If you are still unwell after 24 hours of starting treatment, you should complete the 3-day course, but if your symptoms are much improved, there is no need to continue treatment.

Empirical azithromycin (ciprofloxacin contraindicated)

Age from 6 months to 2 years 11 months
Azithromycin susp: child weighs < 15kg
Azithromycin 200mg/5ml oral suspension
*WEIGHT REQUIRED* Take 10mg per kg bodyweight ONCE a day for 3 days.
Supply 15 ml.
Age: from 6 months to 2 years 11 months
Licensed use: no - off-label indication
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If the child is still unwell after 24 hours of starting treatment, the child should complete the 3-day course, but if the symptoms are much improved, there is no need to continue treatment. The suspension must be reconstituted using safe drinking water.
Age from 3 years to 7 years 11 months
Azithromycin susp: child weighs 15-25kg
Azithromycin 200mg/5ml oral suspension
Take one 5ml spoonful once a day for 3 days.
Supply 15 ml.
Age: from 3 years to 7 years 11 months
Licensed use: no - off-label indication
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If the child is still unwell after 24 hours of starting treatment, the child should complete the 3-day course, but if the symptoms are much improved, there is no need to continue treatment. The suspension must be reconstituted using safe drinking water.
Age from 8 years to 11 years 11 months
Azithromycin susp: child weighs 26-35kg
Azithromycin 200mg/5ml oral suspension
Take 7.5ml once a day for 3 days.
Supply 22 ml.
Age: from 8 years to 11 years 11 months
Licensed use: no - off-label indication
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If the child is still unwell after 24 hours of starting treatment, the child should complete the 3-day course, but if the symptoms are much improved, there is no need to continue treatment. The suspension must be reconstituted using safe drinking water.
Age from 12 years to 13 years 11 months
Azithromycin susp: child weighs 36-45kg
Azithromycin 200mg/5ml oral suspension
Take two 5ml spoonfuls once a day for 3 days.
Supply 30 ml.
Age: from 12 years to 13 years 11 months
Licensed use: no - off-label indication
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If the child is still unwell after 24 hours of starting treatment, the child should complete the 3-day course, but if the symptoms are much improved, there is no need to continue treatment. The suspension must be reconstituted using safe drinking water.
Age from 14 years onwards
Azithromycin tabs: adults and children > 45kg
Azithromycin 500mg tablets
Take one tablet daily for 3 days.
Supply 3 tablets.
Age: from 14 years onwards
Licensed use: no - off-label indication
Private prescription: yes
Patient information: To be taken when symptoms are moderate to severe (for example, bowel movements becoming very frequent, very watery, or contain blood) or if symptoms are lasting beyond 3 days. If you are still unwell after 24 hours of starting treatment, you should complete the 3-day course, but if your symptoms are much improved, there is no need to continue treatment.

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