Drug Prophylaxis for Travelers' Diarrhea
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
TRAVEL MEDICINE INVITED ARTICLE
Charles D. Ericsson and Robert Steffen, Section Editors
Drug Prophylaxis for Travelers’ Diarrhea
Pamela Rendi-Wagner and Herwig Kollaritsch
Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, Vienna, Austria
Travelers’ diarrhea is the most common health impairment in persons visiting developing countries, affecting 20% to 150%
of tourists. Although it is usually benign, travelers’ diarrhea represents a considerable socioeconomic burden for both the
traveler and the host country. The most common enteropathogens are enterotoxigenic and enteroaggregative Escherichia coli.
Travelers’ compliance with dietary precautionary measures is poor. Despite the excellent protection rates provided by anti-
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
biotics, routine administration of prophylaxis is currently not recommended because of potential adverse reactions. Of the
various antibiotics that have been tested, quinolones are considered to be the first choice worldwide; however, quinolone-
resistant pathogens are increasingly being isolated. Because it is frequently administered and provides only moderate pro-
tection, bismuth subsalicylate is not considered a recommendable option for prophylaxis in Europe, where it is rarely available
anyhow. To date, no probiotic has been able to demonstrate clinically relevant protection worldwide. In conclusion, there is
no satisfactory prophylactic option, and worldwide monitoring of antimicrobial susceptibility patterns and the search for
novel antimicrobial agents, such as nonabsorbed antibiotics, and nonantibiotic medications should continue.
Diarrheal illness is by far the most common health impairment costs associated with medication, medical services, canceled ac-
associated with international tourism in terms of frequency and tivities, and change of itinerary) and the destination country (by
economic impact. Today, 150 million people travel each year causing loss of income from tourism) [3–6].
from developed countries to developing countries, and 20% to In most studies, classic TD is defined as passage of ⭓3 un-
150% of these travelers report being affected by this distressing formed stools in a 24-h period with ⭓1 accompanying symp-
condition during the first 2 weeks of their stay, with the like- tom of enteric disease, such as nausea, vomiting, abdominal
lihood of acquiring this condition depending on well-known cramps, fever, tenesmus, or bloody stool [6]. The definition of
risk factors, such as origin and destination of travel, travel TD should also include episodes of diarrhea that occur during
season, and various host factors [1–3]. When data since the the first 7–10 days after the traveler returns home. Illness lasts
late 1970s are assessed, no relevant difference—in particular, 11 week in 8%–15% of patients and 11 month in up to 2%
no decrease in the incidence of travelers’ diarrhea (TD)—can of patients. Approximately 20% of patients with TD are con-
be observed, despite the efforts made by the tourist industry fined to bed for ∼1–2 days [2, 7]. Patients who are at special
to improve local infrastructure (e.g., water treatment, sanita- risk, however, such as small children, pregnant women, elderly
tion, heath care) [2, 3]. patients, and patients with preexisting illnesses, are at an in-
Although TD is self-limited (duration, ∼3–4 days) and benign creased risk of developing complicated and long-lasting disease
in most cases, it causes remarkable discomfort and inconvenience [8, 9]. Other complications may include dehydration (partic-
for the traveler, who is consequently unable to pursue planned ularly in children), reactive arthritis, postinfectious enteropathy,
activities. Moreover, TD represents a considerable socioeconomic and Campylobacter jejuni–associated Guillain-Barré syndrome
burden from the perspective of both the traveler (by incurring [2, 10, 11].
The incidence of TD is not influenced by the patient’s sex.
However, teenagers and young adults have been found to be
Received 31 July 2001; revised 26 October 2001; electronically published 16 January 2002.
at higher risk, most likely because of the ingestion of larger
Reprints or correspondence: Dr. Herwig Kollaritsch, Dept. of Specific Prophylaxis and Tropical
Medicine, Institute of Pathophysiology, University of Vienna, Kinderspitalgasse 15, A-1095 volumes of potentially contaminated food and an adventurous
Vienna, Austria (herwig.kollaritsch@univie.ac.at). lifestyle [3, 4, 12]. Several findings suggest that, although strict
Clinical Infectious Diseases 2002; 34:628–33
2002 by the Infectious Diseases Society of America. All rights reserved.
alimentary hygiene may help minimize the risk of acquiring
1058-4838/2002/3405-0011$03.00 TD, it will definitely not eliminate that risk, because motiva-
628 • CID 2002:34 (1 March) • TRAVEL MEDICINEtional problems on the part of the traveler exist despite exten- to find effective and well-tolerated prophylaxis for travel-as-
sive pretravel counseling [4, 13–15]. Therefore, intensive efforts sociated gastrointestinal disorders. Different types of drugs, in-
have been undertaken to find an effective prophylactic medi- cluding nonantibiotic agents and prophylactic antibiotics, can
cation to prevent TD. Various classes of drugs and means of be considered for the prevention of TD.
prophylaxis have been investigated, including nonantimicrobial Antibiotics. Despite the excellent protection rates provided
agents, antibiotics, and, more recently, the administration of by antibiotics, routine administration of prophylactic antimi-
immunizations. crobial agents is currently not recommended to the healthy
traveler who would just prefer not to experience TD [19–21].
In 1985, a Consensus Conference at the National Institute of
ETIOLOGY
Health confirmed the protective effect of antibiotics for TD
TD is usually caused by ingestion of food and beverages that prevention, but disclaimed a general recommendation of TD
are contaminated with fecal matter. Various infectious agents prophylaxis for widespread use because of potential drug-as-
have been identified, and their prevalences differ remarkably sociated adverse reactions [21]. One of the first antibiotics stud-
according to season and geographical region [16]. Bacteria are ied was doxycycline (100 mg/d), which demonstrated effec-
the most common enteropathogens and are responsible for up tiveness because tetracyclines have a broad spectrum of
to 80% of all cases of TD. The most common bacteria are coverage of TD pathogens. Unfortunately, doxycycline-resistant
enterotoxigenic Escherichia coli, the recently identified entero- strains evolved in many targeted tourist destinations, which
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
aggregative E. coli, Shigella species, Campylobacter jejuni, Sal- limited its potential use in TD therapy and prophylaxis [22,
monella species, and Aeromonas species [8, 17]. Enteric path- 23]. In the early 1980s, other systemic antimicrobials, such as
ogens other than bacteria (protozoa such as Entamoeba trimethoprim-sulfamethoxazole, were also used successfully
histolytica and Giardia lamblia, or enteroviruses) are generally [24, 25] until increasing drug resistance limited their applica-
less important as causes of TD. TD due to Rotavirus and Cam- tion to certain areas and seasons, such as inland Mexico during
pylobacter species is found more frequently in areas with dry the summer [26, 27].
winters [16]. In a considerable proportion (up to 20%) of cases In the past 10 years, 4-fluoroquinolones (norfloxacin, cip-
of TD, however, ⭓2 potentially enteropathogenic agents could rofloxacin, fleroxacin, ofloxacin, and levofloxacin) have at-
be isolated in the course of the same episode [3]. Depending tracted considerable attention as a result of their excellent safety
on the study, 20%–50% of all cases of TD remain of undeter- profile and wide spectrum of coverage of enteropathogenic
mined etiology, despite excellent experimental accuracy and agents [14, 28–31]. It was shown, when taken daily in a single
optimal laboratory evaluation [8, 13]. Most of these cases may low dose—for instance, 400 mg of norfloxacin per day [31] or
be caused by enteropathogenic bacteria or their toxins, because 250 mg of ciprofloxacin per day [29]—the protection against
the disease can be suppressed by prophylactic use of antimi- TD is up to 90%, providing that the enteropathogens present
crobial agents. Speculations about noninfectious causes of TD, in the region of study were susceptible to the agent. Thus far,
such as changes in normal gastrointestinal flora caused by a insufficient data exist to recommend lower doses, although one
different diet or excessive alcohol consumption, are usually can speculate that these doses might be sufficient. However,
unjustified, because the documented benefit of prophylactic the total duration of intake should not exceed 3 weeks, because
antibacterial agents is ∼90%, which implies that TD is mainly the potential for long-term adverse reactions is unknown, and
caused by bacteria or their toxins. individual antimicrobial resistance may be induced [32, 33].
To date, fluoroquinolones have maintained excellent in vitro
activity against most bacterial pathogens associated with TD,
CHEMOPROPHYLAXIS
although the increasing resistance and in vivo emergence of
Although TD is usually mild and self-limiting, there is still a resistance of C. jejuni to quinolones reported from Thailand
need for safe and effective means of prevention. Because con- and Southeast Asia are a matter for serious concern [34–36].
taminated food or beverages are the most important vehicle of Isolation of quinolone-resistant E. coli strains remained rare
transmission of all pathogens that cause TD, precautions re- until 1990; starting in 1990, quinolones have been used for
garding dietary habits (the rule of “boil it, cook it, peel it, or treatment on a widespread scale. Unfortunately, the situation
forget it!”) remain the cornerstone of prevention. However, the is evolving, and resistant strains are increasingly being isolated,
impact of pretravel health advice on the incidence of TD re- particularly in Asia [37].
mains unsatisfactory, mostly because there are problems in mo- Thus far, quinolones remain the drugs of choice when che-
tivating the traveler into taking precautions regarding what to moprophylaxis is indicated for, for instance, patients with severe
eat and drink [4, 13–15, 18]. baseline disease. However, side effects have been observed, such
Since the late 1970s, extensive efforts have been undertaken as skin rash, vaginal candidiasis, CNS reactions, phototoxicity,
TRAVEL MEDICINE • CID 2002:34 (1 March) • 629and gastrointestinal complaints; and, very rarely, there have of up to 65%. This agent has been shown to have short-term
been severe events, including anaphylaxis (table 1) [5, 38]. intraluminal antibacterial action in the prevention of TD [43,
Moreover, confusion might occur with regard to how to man- 44, 52]. Optimal protection rates were reported when the sub-
age an illness that occurs despite the patient’s receipt of anti- stance was administered as 2 tablets 4 times daily (2.1 g/day)
biotic prophylaxis. Quinolones are not approved for prophy- for a maximum period of 3 weeks, because it seems that the
laxis in children and pregnant women. optimal antibacterial effect is provided by simultaneous inges-
Ampicillin, like most other penicillins, is not useful as a tion of contaminated food and BSS [43, 52]. Wine, which is
therapeutic or prophylactic agent because of widespread resis- anecdotally reported to have some sort of preventive effect,
tance and incomplete coverage of TD-causing pathogens [42]. when compared with BSS, was shown to have an equivalent
The spectrum of mecillinam, another penicillin, includes effect in reducing the number of viable organisms; however,
mainly gram-negative aerobic microorganisms, but mecillinam the clinical relevance of these data remains doubtful [53].
lacks effectiveness against such pathogens as enterococci be- The most commonly reported adverse reactions associated
cause it shows selection of resistant pathogens in fecal flora. with BSS were transient blackening of tongue and stools, con-
The new macrolides, such as clarithromycin, have been noted
stipation, tinnitus, and nausea (table 1) [43, 44]. It should be
to significantly impair the oropharyngeal and intestinal micro-
noted that BSS can deplete the absorption of doxycycline, re-
flora by causing overgrowth of new enterobacteria and to select
ducing its circulating levels, a fact that may be of importance
highly resistant isolates when used for prolonged periods, which
with regard to malaria prophylaxis with doxycycline [54]. In
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
makes their application for long-term prophylactic purposes
most European countries, however, BSS preparations are not
unsuitable [45–48].
licensed and are considered an attractive option for neither
Because of the spread in resistance to quinolones, there is great
prophylactic nor therapeutic use. A rather large number of
interest in the development of novel antimicrobial agents that
tablets has to be taken per day; the side effects simply make
are minimally absorbed from the gut, which would thereby attain
high intestinal levels and avoid serious (although rare) toxicity BBS an unattractive option for travelers, and the high level of
of systemic drugs in treatment and prophylaxis. In recent studies, compliance is rewarded by only moderate protection.
rifaximin, a rifamycin derivative with broad-spectrum antibac- Probiotics. Another approach to the prevention of TD is
terial activity [49], has shown promising results with regard to the use of probiotics, which are attractive in view of their lack
safety and efficacy for the treatment of patients with bacterial of toxicity and drug interactions. Protective mechanisms that
infectious diarrhea who traveled to Mexico, Guatemala, and may play a role in the concept of action of these medications
Kenya [50, 51]. This agent, which is presently used in Italy to include the production of acids, hydrogen peroxide, or anti-
treat enteric bacterial infection, should be considered as a po- microbial substances, as well as the competition for nutrients
tential prophylactic candidate that deserves to be evaluated spe- or adhesion receptors, antitoxin action, and stimulation of the
cifically for the purpose of TD prophylaxis. immune system [55]. Many health-related claims have been
Bismuth subsalicylate. A number of studies have con- made concerning probiotics, especially with regard to their po-
firmed that bismuth subsalicylate (BSS) has a protective efficacy tential to prevent and cure intestinal disturbances; however,
Table 1. Prophylactic drugs used to prevent travelers’ diarrhea.
Protective
Drug efficacy, % Side effects Geographic factors References
Probiotics
Lactobacilli GG 0–50 None Depends on the destination [39, 40]
Saccharomyces boulardii 0–60 None Effective in North Africa and Turkey [41]
Antibiotics
Fluoroquinolones 80–100 Nausea, gastrointestinal complaints, Resistance of Campylobacter species [28–31,
vaginitis, anaphylaxis, CNS effects in Thailand and Southeast Asia 34–38, 42]
TMP-SMZ 79–94 Headache, nausea, vaginitis, anaphylaxis, Effective in inland Mexico in summer [25–27]
Stevens-Johnson syndrome
Doxycycline 59–86 Gastrointestinal complaints, vaginitis, Widespread resistance worldwide [22, 23]
photosensitivity, anaphylaxis
Bismuth subsalicylate 40–65 Black tongue and stools, constipation, None [41, 43, 44]
tinnitus, encephalopathya
NOTE. TMP-SMZ, trimethoprim-sulfamethoxazole.
a
Although it is rare, encephalopathy may develop in patients with AIDS after administration of excessive doses.
630 • CID 2002:34 (1 March) • TRAVEL MEDICINEonly a few probiotic agents have been shown to be effective in However, doctors should be conservative in prescribing che-
randomized controlled trials (table 1). moprophylaxis to these travelers.
Oksanen et al. [39] reported that Lactobacillus GG prophy- In any case, chemoprophylaxis should not be recommended
laxis given to tourists traveling to Turkey led to a 12% reduction for long-term travel (duration, 13 weeks) because of increased
of TD; however, the effect was significant only for 1 destination. toxicity and interference with the development of natural im-
In another double-blind, randomized, controlled trial, the risk munity to a number of enteric pathogens, especially entero-
of TD was 4% in American travelers who received Lactobacillus toxigenic E. coli. Besides, prophylaxis may provoke the false
GG (dose, 2 ⫻ 109) and 7% in the control group, which in- impression of security, leading the traveler to take fewer pre-
dicates that there was minimal, although significant, protection cautions in food selection and thereby causing a relative in-
[40]. No protective effect, however, was evident in studies of crease in the incidence of nonbacterial diarrhea. In making a
other lactobacilli, such as Lactobacillus fermentum and Lacto- decision about the use of prophylaxis, the benefits of TD pre-
bacillus acidophilus, because various strains seem to differ in vention need to be clearly balanced against the advantages of
their potential for colonization of the intestine [39, 56, 57]. a simple 1- or 2-day, highly effective, self-administered therapy
A mild but significant and dose-dependent (250 mg and 1000 begun early in the course of diarrhea.
mg) protection against TD with a varying regional effect was The groups that are most seriously affected by TD are small
reported for travelers to North Africa and Turkey who were children and pregnant women. For both of these groups, neither
taking Saccharomyces boulardii [41]. The evaluation of an “oral quinolone-based prophylaxis nor treatment are approved. This
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
vaccine,” which consisted of 1011 heat-inactivated Enterobac- limitation, plus the fact that none of the current options for
teriaceae (Dodecoral; Serotherapeutisches Institut) did not ef- prophylactic medication are entirely satisfactory for broad use
fectively reduce the incidence of TD [57]. because of discouraging protective efficacy, potential adverse
On the basis of these data, the principal concept of protection events, and the increasing prevalence of drug resistance, means
mediated by nonpathogenic bacteria remains appealing, but that alternative options for the prevention of TD are clearly
until now, no probiotic medication has been demonstrated to required.
provide clinically relevant worldwide protection against TD; It is possible that immunoprophylaxis will be developed, but
therefore, a general recommendation for the use of such prep- the chances that a vaccine will be effective are limited, because
arations cannot be provided. It would be worthwhile to inten- the etiology of TD is extremely variable, and it would be difficult
sify research on probiotics, because these medications are low- for even a “broad-spectrum vaccine” to sufficiently cover a great
priced and have excellent safety profiles and acceptance, making variety of TD-causing pathogens and to protect travelers in a
them ideal for tourist self-medication (particularly for persons clinically relevant manner [58–60].
in high-risk groups, such as children and pregnant women).
CONCLUSIONS
GENERAL CONSIDERATIONS
Although most episodes of TD are benign and self-limiting in
A cost-effectiveness analysis that simply compares the cost of healthy adults, considerable morbidity and disruption to travel
chemoprophylaxis with the cost of treatment of patients with results. Therefore, effective prophylaxis against infectious di-
TD shows that prevention of TD in short-term travelers is cost arrhea in travelers is desirable, because travelers put pressure
effective. The most important contributor to the mean cost of on doctors to provide pretravel health advice. A generally ac-
TD was the cost associated with a day of incapacitation asso- ceptable prophylactic agent should meet the following basic
ciated with illness [5]. Thus, prophylaxis may be recommended requirements: it should provide protection to at least 75% of
once the risks and benefits are clearly understood by the patient. travelers, it should have an optimal safety profile for use as
Prophylaxis would be particularly desirable for management of self-medication (and should also be suitable for use by children
conditions with severe baseline disease, such as chronic gas- and pregnant women), administration should be simple (pref-
trointestinal, immunologic (including HIV), endocrinologic, erably a single dose taken daily), there should be no drug re-
and hematologic disorders; it would also be attractive for use sistance problems or drug interactions, and, finally, it should
by travelers who are regularly affected by serious (perhaps ge- be inexpensive. Rifaximin, which shows considerable phar-
netically based) TD [3]. A person with one of these disorders macologic and safety advantages over the existing drugs, might
should definitely be considered a candidate for chemoprophy- prove to be a candidate.
laxis. In addition, chemoprophylaxis should be considered for For now, worldwide monitoring of antimicrobial susceptibility
persons who request preventive medication for important patterns and the search for new antimicrobial agents and non-
short-term trips abroad, such as politicians or businesspeople. antibiotic options of prophylaxis of TD should be intensified.
TRAVEL MEDICINE • CID 2002:34 (1 March) • 631References teers working in Latin America and the Caribbean. J Travel Med 1994;1:
36–42.
1. World Health Organization. The World Health Report 1996: report of 25. Sack RB. Antimicrobial prophylaxis of travelers’ diarrhea: a summary
the Director-General. Geneva: World Health Organization, 1996:5. of studies using doxycycline or trimethoprim and sulfamethoxazole.
2. Steffen R, Van der Linde F, Gyr K, Schär M. Epidemiology of diarrhea Scand J Gastroenterol Suppl 1983; 84:111–7.
in travelers. JAMA 1983; 249:1176–80. 26. Bandres JC, Mathewson JJ, Ericsson CD, et al. Trimethoprim/sulfame-
3. Steffen R, Collard F, Tornieporth N, et al. Epidemiology, etiology, and thoxazole remains active against enterotoxigenic Escherichia coli and Shi-
impact of traveler’s diarrhea in Jamaica. JAMA 1999; 281:811–7. gella species in Guadelajara, Mexico. Am J Med Sci 1992; 303:289–91.
4. Peltola H, Gorbach SL. Travelers’ diarrhea: epidemiology and clinical 27. Murray BE, Alvarado T, Kim K-H, et al. Increasing resistance to tri-
aspects. In: DuPont HL, Steffen R, eds. Textbook of travel medicine methoprim-sulfamethoxazole among isolates of Escherichia coli in de-
and health. Hamilton, Canada: BC Decker, 1997:151–9. veloping countries. J Infect Dis 1985; 152:1107–13.
5. Reeves RR, Johnson PC, Ericsson CD, et al. A cost-effectiveness com- 28. Wistrom J, Norrby SR, Burman LG, Lundholm R, Jellheden B, Englund
parison of the use of antimicrobial agents for treatment or prophylaxis G. Norfloxacin versus placebo for prophylaxis against travelers’ diar-
of travelers’ diarrhea. Arch Intern Med 1988; 148:2421–7. rhea. J Antimicrob Chemother 1987; 20:563–74.
6. Von Sonnenburg F, Tornieporth N, Waiyaki P, et al. Risk and aetiology 29. Parry H, Howard AJ, Galpin OP, Hassan SP. The prophylaxis of trav-
of diarrhea at various tourist destinations. Lancet 2000; 356:133–4. elers’ diarrhea: a double-blind placebo controlled trial of ciprofloxacin
7. Ericsson CD, DuPont HL. Travelers’ diarrhea: approaches to prevention during a Himalayan expedition. J Infect 1994; 28:337–8.
and treatment. Clin Infect Dis 1993; 16:616–24. 30. Scott DA, Haberberger RL, Thornton SA, Hyams KC. Norfloxacin for
8. DuPont HL, Ericsson CD. Prevention and treatment of travelers’ di- the prophylaxis of travelers’ diarrhea in US military personnel. Am J
arrhea. N Engl J Med 1993; 328:1821–7. Trop Med Hyg 1990; 42:160–4.
9. Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of 31. Johnson PC, Ericsson CD, Morgan DR, et al. Lack of emergence of
travelers’ diarrhea in infants and children. Pediatr Infect Dis J 1991; resistant fecal flora during successful prophylaxis of traveler’s diarrhea
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
10:719–23. norfloxacin. Antimicrob Agents Chemother 1986; 30:671–4.
10. Rees JH, Soudain SE, Gregson NA, Hughes RAC. Campylobacter jejuni 32. Ericsson CD, Mattila L. Prevention of travelers’ diarrhea: risk avoidance
infection and Guillain-Barré syndrome. N Engl J Med 1995; 333: and chemoprophylaxis. In: DuPont HL, Steffen R, eds. Textbook of
1374–9. travel medicine and health. Hamilton, Canada: BC Decker, 1997:
11. Taylor DN, Connor BA, Shlim DR. Chronic diarrhea in the returned 159–64.
traveler. Med Clin North Am 1999; 83:1033–52. 33. Wiström J, Gentri LO, Palmgren AC, et al. Ecological effects of short-
12. Kollaritsch H. Travelers’ diarrhea in Austrian tourists in warm climates term ciprofloxacin treatment of travelers’ diarrhea. J Antimicrob
countries. Eur J Epidemiol 1989; 5:74–81. Chemother 1992; 30:693–706.
13. Peltola H. Travelers’ diarrhea: epidemiology and risk factors [abstract 34. Hoge CW, Gambet JM, Srijan A, Pitarangsi C, Echeverria P. Trends in
SY05.01]. In: Program and abstracts of the 7th Conference of the antibiotics resistance among diarrhea pathogens isolated in Thailand
International Society of Travel Medicine (ISTM; Innsbruck, Austria). over 15 years. Clin Infect Dis 1998; 26:341–5.
Innsbruck, Austria, ISTM, 2001. 35. Kuschner R, Trofa AF, Thomas RJ, et al. Use of azithromycin for the
14. Herwaldt BL, De Arroyave KR, Roberts JM, Juranek DD. A multiyear treatment of Campylobacter enteritis in travelers to Thailand, an area
prospective study of the risk factor for and incidence of diarrheal illness where ciprofloxacin resistance is prevalent. Clin Infect Dis 1995; 21:
in a cohort of Peace Corps volunteers in Guatemala. Ann Intern Med 536–41.
2000; 132:982–8. 36. Gaudreau C, Glibert H. Antimicrobial resistance of clinical strains of
15. Mattila L, Siitonen A, Kyrönseppä H, et al. Risk behavior for travelers’ Campylobacter jejuni subsp. jejuni isolated from 1985–1997 in Quebec,
diarrhea among Finnish travellers. J Travel Med 1995; 2:77–84. Canada. Antimicrob Agents Chemother 1998; 42:2106–8.
16. Mattila L, Siitonen A, Kyronseppa H, et al. Seasonal variation in eti- 37. Cheong H-J, Yoo C-W, Sohn J-W, et al. Bacteremia due to quinolone-
ology of travelers’ diarrhea. Finnish-Moroccan Study Group. J Infect resistant Escherichia coli in a teaching hospital in South Korea. Clin
Dis 1992; 165:385–8. Infect Dis 2001; 33:48–53.
17. Adachi JA, Jiang ZD, Mathewson JJ, et al. Enteroaggregative Escherichia 38. Stahlmann R, Lode H. Toxicity of quinolones. Drugs 1999; 58(Suppl
coli as a major etiologic agent in traveler’s diarrhea in 3 regions of the 2):37–42.
world. Clin Infect Dis 2001; 32:1706–9. 39. Oksanen PJ, Salminen S, Saxelin M, et al. Prevention of travelers’
18. Kozicki M, Steffen R, Schär M. “Boil it, cook it, peel it or forget it”: diarrhea by Lactobacillus GG. Ann Med 1990; 22:53–6.
does this rule prevent travellers’ diarrhea? Int J Epidemiol 1985; 14: 40. Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus
169–72. GG as a diarrheal preventive in travelers. J Travel Med 1997; 4:41–3.
19. Ryan ET, Kain KC. Health advice and immunization for travelers. N 41. Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prophylaxe der
Engl J Med 2000; 342:1716–25. Reisediarrhöe mit Saccharomyces boulardii [Prevention of travelers’ di-
20. Steffen R, Kollaritsch H, Fleischer K. Travelers’ diarrhea in the new arrhea by Saccharomyces boulardii: results of a placebo-controlled dou-
millennium—consensus among experts from German-speaking coun- ble-blind study]. Fortschr Med 1993; 11:153–6.
tries. J Travel Med 2001 (in press). 42. Gomi H, Jiang ZD, Adachi JA, et al. In vitro antimicrobial susceptibility
21. Gorbach SL, Edelman R, eds. Travelers’ diarrhea: National Institutes testing of bacterial enteropathogens causing travelers’ diarrhea in four
of Health Consensus Development Conference. Rev Infect Dis 1986; geographic regions. Antimicrob Agents Chemother 2001; 45:212–6.
8(Suppl 2):109–233. 43. Steffen R, DuPont HL, Heusser R, et al. Prevention of travelers’ di-
22. Sack RB, Santosham M, Froehlich JL, Medina C, Ørskov F, Ørskov I. arrhea by the tablet form of bismuth subsalicylate. Antimicrob Agents
Doxycycline prophylaxis of travelers’ diarrhea in Honduras, an area Chemother 1986; 29:625–9.
where resistance to doxycycline is common among enterotoxigenic 44. Graham DY, Estes MK, Gentry LO. Double-blind comparison of bis-
Escherichia coli. Am J Trop Med Hyg 1984; 33:460–6. muth-subsalicylate and placebo in the prevention and treatment of
23. Sack DA, Kaminsky DC, Dack RB, et al. Prophylactic doxycycline for enterotoxigenic Escherichia coli–induced diarrhea in volunteers. Gas-
travelers’ diarrhea: results of a prospective double-blind study of Peace troenterology 1983; 85:1017–22.
Corps volunteers in Kenya. N Engl J Med 1978; 298:758–63. 45. Beyer G, Hiemer-Bau M, Ziege S, et al. Impact of moxifloxacin versus
24. Heck JE, Staneck JL, Cohen MB, et al. Prevention of travelers’ diarrhea: clarithromycin on normal oropharyngeal microflora. Eur J Clin Mi-
ciprofloxacin versus trimethoprim/sulfamethoxazole in adult volun- crobiol Infect Dis 2000; 19:548–50.
632 • CID 2002:34 (1 March) • TRAVEL MEDICINE46. Brismar B, Edlund C, Nord CE. Comparative effects of clarithromycin antimicrobial effects of bismuth salicylate and red and white wine. BMJ
and erythromycin on the normal intestinal microflora. Scand J Infect 1995; 311:1657–60.
Dis 1991; 23:635–42. 54. Ericsson CD, Pickering LK, Sullivan P, Cleary TG. Influence of sub-
47. Edlund C, Beyer G, Hiemer-Bau M, et al. Comparative effects of moxi- salicylate bismuth on absorption of doxycycline. JAMA 1982; 247:
floxacin and clarithromycin on the normal intestinal microflora. Scand 2266–7.
J Infect Dis 2000; 32:81–5. 55. Marteau PR, de Vrese M, Cellier CJ, Schrezenmeir J. Protection from
48. Edlund C, Alván G, Barkholt L, et al. Pharmacokinetics and compar- gastrointestinal disease with the use of probiotics. Am J Clin Nutr
ative effects telithromycin (HMR 3647) and clarithromycin on the 2001; 73(Suppl):430S–6S.
oropharyngeal and intestinal microflora. J Antimicrob Chemother 56. Katelaris PH, Salam I, Farthing MJG. Lactobacilli to prevent traveler’s
2000; 46:741–9. diarrhea? N Engl J Med 1995; 333:1360–1.
49. Hoover W, Gerlach E, Hohan D, Eliopoulos G, Pfaller M, Jones R.
57. Kollaritsch H, Kremsner P, Wiedermann G, Scheiner O. Prevention of
Antimicrobial activity and spectrum of rifaximin, a new tropical ri-
traveler’s diarrhea: comparison of different non-antibiotic prepara-
famycin deviate. Diagn Microbiol Infect Dis 1993; 16:111–8.
tions. Travel Med Int 1989; 9–17.
50. DuPont HL, Steffen R, Sack DA, et al. A randomized, double-blind,
58. Peltola H, Siitonen A, Kryoneseppa H, et al. Prevention of travelers’
parallel, placebo-controlled study of rifaximin at 600 and 1200 mg/
diarrhea by oral B-subunit/whole-cell cholera vaccine. Lancet 1991;
day in the treatment of bacterial infectious diarrhea in travelers [ab-
stract FC01.01]. In: Program and abstracts of the 7th Conference of 338:1285–9.
the International Society of Travel Medicine (ISTM; Innsbruck, Aus- 59. Wiedermann G, Kollaritsch H, Kundi M, Svennerholm AM, Bjare U.
tria). Innsbruck, Austria: ISTM, 2001. Double-blind, randomized, placebo controlled pilot study evaluating
51. DuPont HL, Ericsson CD, Mathewson JJ, et al. Rifaximin: a non- efficacy and reactogenicity of an oral ETEC B-subunit–inactivated
absorbed antimicrobial in the therapy of travelers’ diarrhea. Digestion whole cell vaccine against travelers’ diarrhea (preliminary report). J
1998; 59:708–14. Travel Med 2000; 7:27–9.
Downloaded from http://cid.oxfordjournals.org/ by guest on October 12, 2015
52. DuPont HL, Ericsson CD, Johnson PC, et al. Prevention of travelers’ 60. Svennerholm AM. Enteric vaccines [abstract SY05.03]. In: Program
diarrhea by the tablet formulation of bismuth subsalicylate. JAMA and abstracts of the 7th Conference of the International Society of
1987; 257:1347–50. Travel Medicine (ISTM; Innsbruck, Austria). Innsbruck, Austria: ISTM,
53. Weisse ME, Eberly B, Person DA. Wine as a digestive aid: comparative 2001.
TRAVEL MEDICINE • CID 2002:34 (1 March) • 633You can also read
