There is consistent evidence from double-blind trials that antibiotic treatment is more effective than placebo at preventing diarrhoea in healthy adults travelling to countries with a high risk of traveller's diarrhoea (for example Mexico, Africa, Asia, and Latin America). One study found no difference between antibiotic and placebo for people travelling to low-risk countries (Mediterranean Europe or the Canary Islands). Duration of antibiotic treatment was 1–3 weeks.

CKS identified no systematic reviews or meta-analyses on the use of antibiotics for preventing traveller's diarrhoea. Ten double-blind randomized controlled trials (RCTs) were identified which compared antibiotic treatment with placebo and/or another antibiotic. All the trials involved healthy adults, with treatment taken for 1–3 weeks. Trials were generally small and reported that antibiotic treatment was well tolerated.

Although there is evidence supporting the use of co-trimoxazole, doxycycline, and trimethoprim, these antibiotics 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].

• Ciprofloxacin compared with placebo
• One double-blind RCT (in 54 Dutch travellers staying in first-class hotels in Tunisia) found ciprofloxacin 500 mg daily for one week was more effective than placebo in reducing the number of people who experienced diarrhoea (4% versus 64% respectively, p < 0.0001) [Rademaker et al, 1989].
• Ciprofloxacin compared with co-trimoxazole and placebo
• In one double-blind RCT in 278 adult volunteers working in Latin America and the Caribbean, the number of people experiencing diarrhoea was lower in the groups taking ciprofloxacin 500 mg daily for 2 weeks (5%) or co-trimoxazole 960 mg daily for 2 weeks (16%) compared with placebo (33%) [Heck et al, 1994]. Ciprofloxacin was more effective than co-trimoxazole.
• Co-trimoxazole compared with trimethoprim and placebo
• One double-blind RCT (145 US students travelling to Mexico) found that, when given for 2 weeks, fewer people experienced diarrhoea in the groups receiving co-trimoxazole 960 mg (2%, p < 0.0001) or trimethoprim 200 mg (14%, p < 0.05) compared with placebo (33%) [DuPont et al, 1983]. Co-trimoxazole was more effective than trimethoprim (p < 0.05). However, no difference was found between the groups in terms of:
• The severity of clinical illness among those who developed diarrhoea.
• Number of people who developed diarrhoea in the 8-day post-treatment interval (incidence range 23–36%).
• Adverse effects: skin rashes were reported in 3% of people in the co-trimoxazole group and 7% in the trimethoprim group. Three students who received antibiotics withdrew due to generalized skin eruptions.
• Doxycycline compared with placebo
• Four small, double-blind RCTs involving Peace Corps volunteers were identified using doxycycline.
• In the first trial (50 people) undertaken in Morocco, doxycycline 100 mg daily for 3 weeks reduced the number of people experiencing diarrhoea compared with placebo (8% versus 46%, p < 0.01) [Sack et al, 1979]. When treatment was stopped, no difference was found in the number of people developing traveller's diarrhoea.
• Three subsequent studies were undertaken in countries where doxycycline-resistant enterotoxigenic Escherichia coli was known to be common. During the 3 weeks when treatment was taken, no statistical difference was found between placebo and antibiotic groups in two trials: in one trial in Honduras in 46 people, doxycycline 100 mg was taken twice weekly [Santosham et al, 1981], and in the other trial in Thailand in 63 people, doxycycline 100 mg was taken daily [Echeverria et al, 1984]. The third trial in 44 people found doxycycline 100 mg daily for 3 weeks was more effective than placebo (32% experienced diarrhoea versus 100% respectively, p < 0.05) [Sack et al, 1984].
• Norfloxacin compared with placebo
• Three double-blind RCTs were identified. For people travelling to countries with a high risk of traveller's diarrhoea, all three studies found norfloxacin was more effective than placebo at preventing diarrhoea.
• In one RCT in 120 US students travelling to Mexico, only 7% of people taking norfloxacin 400 mg daily for 2 weeks experienced diarrhoea, compared with 61% in the placebo group (p < 0.0001) [Johnson et al, 1986b]. An adverse event was reported: one person in the norfloxacin group developed a generalized skin rash.
• In the second RCT in 127 Swedish travellers to countries outside northern Europe, fewer people travelling to areas with a high risk of traveller's diarrhoea (Africa, Asia, or Latin America) developed diarrhoea in the norfloxacin 200 mg daily group (12.5%) than in the placebo group (53.3%, p = 0.0004) [Wiström et al, 1987]. No difference was found between the two groups for those travelling to low-risk countries (Mediterranean Europe or the Canary Islands). The median duration of treatment in both groups was 15 days (range 7–23 days).
• In the third RCT in 222 US military personnel on shore leave in Egypt, only 2% of the norfloxacin 400 mg daily for 7 days group developed acute diarrhoea, compared with 26% in the placebo group [Scott et al, 1990].
• Rifaximin compared with placebo
• One double-blind RCT in 210 American adults travelling to Mexico found 2 weeks of treatment with rifaximin (200 mg daily, or 200 mg twice daily, or 300 mg three times a day) resulted in fewer people developing diarrhoea (14.74%), compared with placebo (53.70%; rate ratio 0.27, 95% CI 0.17 to 0.43) [DuPont et al, 2005]. Adverse events were comparable in both groups. Rifaximin is not available in the UK.