Traveler's diarrhea

Background

• A diarrheal syndrome which may be caused by a variety of intestinal pathogens contracted while traveling, particularly in low-income countries

Bacteria account for a majority of cases, but traveler's diarrhea may also be caused by parasites or viruses.

• • Is the most common travel-associated disease
  • Greatest contributor to illness poor hygiene in restaurants
• Most cases of traveler’s diarrhea are caused by bacterial enteropathogens, whereas bacterial pathogens cause less than 15% of endemic diarrhea cases in adults living in their home country
  • Most cases respond to antibiotics (as opposed to non-traveler's acute gastroenteritis, which is most commonly caused by viruses)
  • As duration of diarrhea increases, higher chance of parasitic cause
• At risk populations- Immunosuppressed, diabetes, taking meds to suppress acid production

Etiology

Organism	Latin America and Caribbean	Africa	South Asia	Southeast Asia
Enterotoxigenic Escherichia coli	≥35	25-35	15-25	5-15
Enteroaggregative E coli	25-35	<5	15-25	No data
Campylobacter	<5	<5	15-25	25-35
Salmonella	<5	5-15	<5	5-15
Shigella	5-15	5-15	5-15	<5
Norovirus	15-25	15-25	5-15	<5
Rotavirus	15-25	5-15	5-15	<5
Giardia	<5	<5	5-15	5-15

Clinical Features>

Characterized by the following:==

Uncomplicated Diarrhea

• No workup

Fever, Bloody Stools, or Ill Appearing

• Stool culture
• Systemic toxicity
  • Extended workup including blood cultures

Persistent or Refractory Diarrhea (>14 days)

• Typically not done in the ER (at follow-up)
  • Stool culture (including Salmonella, Shigella, and Campylobacter)
  • Stool O&P (including testing for protozoal parasites, Giardia, Cryptosporidium)
  • Fecal leukocytes, giardia antigen, C. difficile PCR

Management

Supportive Care

• Bismuth subsalicylate (Pepto Bismol) ~524 mg every 30 to 60 minutes or 1,050 mg every 60 minutes as needed (maximum: ~4,200 mg/24 hours)
• Consider IVF if dehydrated
• Consider loperamide 4mg PO followed by 2mg after each loose stool (Max: 16mg/day)
  • If very frequent stools and no contra-indication:
    • Not pregnant
    • >2 years old
    • Fever or bloody stools without concomitant antibiotics (do not use as sole therapy)

Antibiotics

• Ciprofloxacin 750mg PO once daily x 1-3 days
  • First choice for use except in South and Southeast Asia
• Azithromycin 500mg PO q24h x 3 days OR 1000mg PO x 1
  • Nausea is a frequent adverse event
  • First choice for use in South and Southeast Asia
• Rifaximin 200mg PO TID x 3 days
  • Ineffective against mucosally invasive pathogens (Shigella, Salmonella, Campylobacter)
  • Considered very safe as it is not absorbed

Pediatrics

Antibiotic Options:

Avoid fluroquinolones

• Azithromycin 10mg/kg/day once daily x 3 days OR
• Ceftriaxone 50mg/kg/day once daily x 3 days

Disposition

• Outpatient for the vast majority
• Consider admission if systemic toxicity

Complications

• Postinfectious irritable bowel syndrome
• Reactive arthritis
• Guillain-Barre syndrome

See Also

• Diarrhea
• Diarrhea (Peds)
• Travel Medicine

External Links

• CDC - Travelers Diarrhea

Differential Diagnosis

The differential diagnosis includes foodborne illnesses less commonly associated with travel, such as: Bacterial gastroenteritis, including: Bacillus cereus food poisoning, which often presents with nausea and vomiting resolving in 12-24 hours Staphylococcus aureus food poisoning, which often presents with acute onset nausea, vomiting, and abdominal cramping resolving in 24-48 hours Clostridium perfringens food poisoning, which often presents as severe watery diarrhea with abdominal cramps and little or no vomiting Listeriosis Helminth infections acquired from fish, such as anisakiasis, typically presenting with nausea and vomiting Food poisoning from marine toxins, including: Ciguatera fish poisoning, in which gastrointestinal symptoms often occur in first 6-24 hours and may be followed by neurologic symptoms, often perioral numbness and paresthesias Scombroid poisoning, which is typically associated with flushing, palpitation, itching due to histamine release, and scombrotoxins, which may be accompanied by diarrhea and abdominal cramps Paralytic shellfish poisoning, in which neurologic symptoms arise 30-60 minutes after ingestion and may be accompanied by nausea, vomiting, and diarrhea Neurotoxic shellfish poisoning, which presents with gastroenteritis accompanied by minor paresthesias/dysesthesias Diarrheic shellfish poisoning, which typically presents with nausea, vomiting, and abdominal cramps Diarrhea caused by Shiga toxin-producing organisms: Antibiotic treatment may increase the release of Shiga toxins and precipitate hemolytic-uremic syndrome (HUS). Antimotility agents should be similarly avoided. Shiga toxin-producing organisms include: Shiga toxin-producing Escherichia coli (STEC), predominantly O157:H7 Shigella dysenteriae serotype 1, a less common cause (see also Bacillary Dysentery) Suspect STEC in patients with: Bloody diarrhea Abdominal pain greater that is typically seen with other forms of bacterial gastroenteritis Painful defecation Fever and leukocytosis are variably present. Reference - Lancet 2005 Mar 19-25;365(9464):1073 See also Foodborne Illnesses. The differential diagnosis also includes early presentations of inflammatory bowel disease such as Crohn disease and ulcerative colitis. See also: Acute Diarrhea in Adults Acute Diarrhea in Children - Approach to the Patient Fever in the Returning Traveler

Evaluation

The diagnosis is made clinically in patients with new onset diarrhea during travel or shortly afterward (within 1-2 weeks). Laboratory testing is not required in most cases, as the diarrhea is often self-limited. Consider the following tests when signs of invasive infection (such as fever, bloody stool, or cholera-like diarrhea with dehydration) are present, or in patients with diarrhea lasting ≥ 14 days: Stool culture for enteropathogens Shiga toxin assay, to rule out Shiga toxin-producing E. Coli (STEC) Fecal leukocyte or lactoferrin testing Molecular assays targeting common enteropathogens When diarrhea persists for ≥ 14 days, consider testing for parasites with: Stool microscopy for ova, cysts, and parasites (O&P). Stool antigen detection for Giardia spp., Cryptosporidium spp., And Entamoeba histolytica parasites. Modified acid-fast staining of stool for Cyclospora spp.

Workup

Evaluation of returned travelers: Testing is typically not required as mild or uncomplicated disease is often self-limited or can be treated empirically.2,4 Indications for laboratory evaluation include:2,3 Diarrhea lasting ≥ 14 days Fever > 101.3 degrees F (38.5 degrees C) Dysentery Cholera-like diarrhea with dehydration ISTM recommends microbiological testing for returning travelers with severe or persistent symptoms, including bloody diarrhea or mucus in stools, or who fail empiric therapy (ISTM Strong recommendation, Low/very low-level evidence). Identification of the etiology may help direct pathogen-specific treatment. Molecular testing to identify broad range of clinically-relevant pathogens is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis (ISTM Ungraded recommendation). Testing may include: Stool culture Stool microscopy to examine for ova, cysts, and parasites Blood culture if bacteremia is suspected Fecal leukocytes or fecal lactoferrin test if bacterial infection is suspected Molecular assays targeting multiple pathogens

Diagnosis

Stool culture for enteropathogens Microscopy and antigen detection to test for parasites Blood tests, including blood culture, if bacteremia is suspected Shiga toxin assay to rule out Shiga toxin-producing Escherichia coli (STEC) Fecal leukocyte or lactoferrin testing Molecular assays for detection of common enteropathogens Blood tests Blood tests may be helpful for patients with persistent, systemic, or severe symptoms and include:2,3 Complete blood count (eosinophilia may indicate schistosomiasis, strongyloidiasis, or other helminthic infection) Liver function tests Renal function tests Inflammatory markers (such as erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) Blood culture if bacteremic salmonellosis (including typhoid fever) is suspected

Management

Most bacterial and viral cases are self-limited and typically resolve in 2-7 days, though parasitic infection may persist for longer if untreated. The severity of illness determines treatment approach. Mild diarrhea is tolerable, not distressing, and does not interfere with planned activities. Moderate diarrhea is distressing or interferes with planned activities. Severe diarrhea is incapacitating or completely prevents planned activities. All dysentery (grossly bloody stools) is considered severe. Self-treatment is the preferred treatment strategy for many travelers as diarrhea often arises during travel. Provide medications to patients prior to travel. Educate patients about preventive measures. Management strategies: All patients with traveler's diarrhea should maintain hydration by drinking clear fluids (fruit juice, soups, tea) and gradually reintroduce regular foods to their diet. The risk of dehydration is higher in very young children or in adults with chronic medical illness. Oral rehydration may help travelers feel better more quickly. Antimotility therapy can be used when rapid control of symptoms is needed (for example, on a long bus ride without a toilet). Loperamide: Consider as monotherapy in patients with mild (ISTM Strong recommendation, Moderate-level evidence) or moderate (ISTM Strong recommendation, High-level evidence) traveler's diarrhea. Loperamide ay be used as adjunctive therapy with antibiotics in patients with moderate-to-severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence). Dosing by age: For patients ≥ 12 years old, dosing is 4 mg orally after the first loose stool, then 2 mg orally after each subsequent loose stool (maximum 16 mg/24 hours; nonprescription maximum of 8 mg/24 hours). For patients 9-11 years old (27 kg-43 kg [60-95 lbs]), dosing is 2 mg orally after the first loose stool, then 1 mg orally after each subsequent loose stool (maximum 6 mg/24 hours). For patients 6-8 years old (21 kg-26 kg [48-59 lbs]), dosing is 2 mg orally after the first loose stool, then 1 mg orally after each subsequent loose stool (maximum 4 mg/24 hours). Do not use loperamide as monotherapy in patients with bloody diarrhea and fever. Bismuth subsalicylate: Consider bismuth subsalicylate in patients with mild traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence). It may reduce nausea. Dosing in adults and children ≥ 12 years old: Regular strength dosing is 525 mg orally every 0.5 to 1 hour as needed, up to a maximum of 8 doses/day (4200 mg/day). Extra strength dosing is 1050 mg orally every 1 hour as needed, up to a maximum of 4 doses in 24 hours (4200 mg/day). Bismuth subsalicylate is not recommended in children < 3 years old and typically not used in children < 12 years old. Antibiotics are recommended for patients with moderate-to-severe diarrhea. Antibiotics may reduce the duration of illness, but may carry an increased risk of adverse events. International Society of Travel Medicine recommendations for antibiotic use in traveler's diarrhea: Antibiotics are not recommended for mild traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence). Consider antibiotic therapy for moderate traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence). Options include: Azithromycin (ISTM Strong recommendation, High-level evidence) Fluoroquinolones (ISTM Strong recommendation, Moderate-level evidence) with qualifications due to the: Emergence of resistance to this drug class, especially in Southeast Asia Potential for adverse dysbiotic and musculoskeletal events Rifaximin (ISTM Weak recommendation, Moderate-level evidence), but caution is suggested when considering rifaximin in regions with a high risk of invasive pathogens Antibiotics are recommended for severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence). Options include: Azithromycin (preferred) (ISTM Strong recommendation, Moderate-level evidence) Fluoroquinolones or rifaximin for severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence) Single-dose regimens are recommended for moderate or severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence). Antibiotics and antimotility agents should be avoided in cases of known or suspected infection with Shiga toxin-producing organisms. While most cases of traveler's diarrhea are caused by bacteria, in cases of known parasitic infection treatment options are based on the causative organism. Preferred options for giardiasis include: 5-nitroimidazoles, such as: Tinidazole 2 g orally single dose (50 mg/kg single dose in children) Metronidazole 250 mg orally 3 times daily (15 mg/kg/day in 3 divided doses for children) for 5-7 days Nitazoxanide 500 mg orally twice daily taken with food for 3 days in adults and children ≥ 12 years old (7.5 mg/kg twice daily for 3 days in children < 12 years old) See Giardiasis for additional information. Cryptosporidiosis may be treated with nitazoxanide. Cyclosporiasis may be treated with trimethoprim-sulfamethoxazole. Amebiasis may be treated with metronidazole or tinidazole, followed by luminal agent such as paromomycin or iodoquinol.

Disposition

Fluoroquinolones International Society of Travel Medicine (ISTM) recommendations suggest fluoroquinolones may be used to treat:5 Moderate traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence), with qualifications due to the: Emergence of resistance to this drug class, especially in Southeast Asia Potential for adverse dysbiotic and musculoskeletal events Severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence) Avoid fluoroquinolones in cases of suspected Shiga toxin-producing Escherichia coli (STEC), due to the potential for increased risk of complications.4 Dosing:1,2,3,5 Levofloxacin 500 mg orally once daily for 1-3 days (single dose can be continued daily for up to 3 days if symptoms do not resolve after 24 hours) Ciprofloxacin: 750 mg orally as single dose (continue daily dosing for up to 3 days if symptoms do not resolve after 24 hours) OR 500 mg orally twice daily for 3 days Ofloxacin 400 mg/day orally for 1-3 days (single dose can be continued daily for up to 3 days if symptoms do not resolve after 24 hours) Norfloxacin 400 mg orally once daily (not available in the United States) Fluoroquinolones may be associated with abdominal discomfort, nausea, insomnia, or irritability.4 Considerations in special populations:4 There have been concerns about transient musculoskeletal effects in children, but ciprofloxacin is considered safe for pediatric patients, particularly for short-course treatment. Use is not routinely advised during pregnancy. STUDY SUMMARY fluoroquinolones appear to be effective in patients with traveler's diarrhea DynaMed Level 2 RANDOMIZED TRIAL: Antimicrob Agents Chemother 1992 Jan;36(1):87

Details Resistance to fluoroquinolones Increasing rates of resistance to fluoroquinolones have been found among causative organisms of traveler's diarrhea.1,5 Impacted pathogens include Campylobacter, Shigella and Salmonella species. Fluoroquinolone resistance is particularly widespread in Southeast and South Asia. STUDY SUMMARY resistance of Campylobacter to fluoroquinolones may be increasing COHORT STUDY: N Engl J Med 1999 May 20;340(20):1525 COHORT STUDY: Emerg Infect Dis 2002 Dec;8(12):1501 COHORT STUDY: Emerg Infect Dis 2003 Feb;9(2):267 COHORT STUDY: Clin Infect Dis 1998 Feb;26(2):341 COHORT STUDY: Am J Trop Med Hyg 2002 Nov;67(5):533

Details Only 25% of Campylobacter jejuni and 33% of Campylobacter coli infections were susceptible to ciprofloxacin in a cohort study of 230 adults with acute diarrhea during a visit to Cusco, Peru between 2003 and 2010 (Am J Trop Med Hyg 2017 May;96(5):1097). Azithromycin International Society of Travel Medicine (ISTM) recommendations for azithromycin:5 Azithromycin may be used to treat moderate traveler's diarrhea (ISTM Strong recommendation, High-level evidence). It is the preferred treatment for severe traveler's diarrhea (including dysentery or febrile diarrhea) (ISTM Strong recommendation, Moderate-level evidence). It is the first-line choice for empiric therapy to cover fluoroquinolone-resistant Campylobacter in Southeast Asia and India, or other areas if there is suspicion of Campylobacter or resistant enterotoxigenic Escherichia coli. Azithromycin is effective against a broad range of pathogens that cause traveler's diarrhea, including Campylobacter infection.2,4 Dosage:1,5 Adult dosing: 1,000 mg orally once (if symptoms are not resolved after 24 hours, continue daily dosing for up to 3 days) 500 mg orally once daily for 3 days Dosing in children: 10 mg/kg orally once daily for 3 days Azithromycin is considered safe for children and pregnant persons.4 It may be associated with pruritus or candida vaginitis.4 Efficacy: Azithromycin 500 mg appears to have similar clinical efficacy compared to ciprofloxacin 500 mg in patients with traveler's diarrhea DynaMed Level 2 . Single dose azithromycin appears at least as effective as single dose levofloxacin for traveler's diarrhea DynaMed Level 2 . Azithromycin 1,000 mg appears to have similar efficacy compared to levofloxacin 500 mg in adults with traveler's diarrhea receiving loperamide DynaMed Level 2 . Azithromycin 1,000 mg orally once appears more effective than a 3-day course of azithromycin 500 mg or levofloxacin 500 mg for resolution of traveler's diarrhea DynaMed Level 2 . See Comparative efficacy of antibiotics for the details of each study. Rifaximin International Society of Travel Medicine (ISTM) recommends rifaximin may be used for treatment of:5 Moderate traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence), but suggest caution when considering rifaximin in regions with high risk of invasive pathogens Severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence) Rifaximin is a poorly absorbed, gut-selective antibiotic.2,5 Rifaximin (Xifaxan) is FDA approved for treatment of patients ≥ 12 years old with traveler's diarrhea caused by noninvasive E. coli. Dose is 200 mg orally three times daily for 3 days. Adverse effects include headache. Reference - FDA DailyMed 2020 Oct 30 STUDY SUMMARY rifaximin may reduce duration of traveler's diarrhea in adults DynaMed Level 2 RANDOMIZED TRIAL: Am J Gastroenterol 2003 May;98(5):1073

Details Rifamycin Rifamycin (Aemcolo) is FDA approved for treatment of traveler’s diarrhea caused by noninvasive Escherichia coli. It is not approved for use in patients with diarrhea complicated by fever or blood in the stool or due to pathogens other than noninvasive strains of Escherichia coli. Dosing and administration: Dosing is 388 mg orally twice daily (in the morning and evening) for 3 days. Take each dose with 6-8 ounces of liquid. Do not take with alcohol. Adverse effects include headache and constipation. Reference - FDA DailyMed 2020 Feb 14 Rifamycin may be considered as an alternative to rifaximin.1