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| {{Diarrhea DDX}} | | {{Diarrhea DDX}} |
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| ==Evaluation<ref name="Steffen"></ref>== | | ==Evaluation== |
| | ''Diagnosis is typically made clinically'' |
| ===Uncomplicated Diarrhea=== | | ===Uncomplicated Diarrhea=== |
| *No workup | | *No workup<ref name="Steffen"></ref> |
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| ===Fever, Bloody Stools, or Ill Appearing=== | | ===Fever, Bloody Stools, or Ill Appearing=== |
| *Stool culture | | *Stool culture <ref name="Steffen"></ref> |
| *Systemic toxicity | | *Systemic toxicity |
| **Extended workup including blood cultures | | **Extended workup including blood cultures |
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| *Typically not done in the ER (at follow-up) | | *Typically not done in the ER (at follow-up) |
| **Stool culture (including [[Salmonella]], [[Shigella]], and [[Campylobacter]]) | | **Stool culture (including [[Salmonella]], [[Shigella]], and [[Campylobacter]]) |
| **Stool O&P (including testing for protozoal parasites, [[Giardia]], [[Cryptosporidium]]) | | **Stool O&P (including testing for protozoal parasites, [[Giardia]], [[Cryptosporidium]])<ref name="Steffen"></ref> |
| **Fecal leukocytes, giardia antigen, C. difficile PCR | | **Fecal leukocytes, giardia antigen, C. difficile PCR |
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| ==Management== | | ==Management== |
| ===Supportive Care=== | | ===Supportive Care=== |
| | *PO hydration and consider [[oral rehydration fluids]] |
| | *Consider [[ondansetron]] if concurrent nausea/vomiting |
| *[[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)<ref>Brum, et al. Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea. Dig Dis Sci. 2021; 66(7): 2323–2335. doi: 10.1007/s10620-020-06509-7</ref> | | *[[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)<ref>Brum, et al. Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea. Dig Dis Sci. 2021; 66(7): 2323–2335. doi: 10.1007/s10620-020-06509-7</ref> |
| *Consider [[IVF]] if dehydrated | | *Consider [[IVF]] if dehydrated |
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| [[Category:Tropical Medicine]] | | [[Category:Tropical Medicine]] |
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| ==Evaluation==
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| The diagnosis is made clinically in patients with new onset diarrhea during travel or shortly afterward (within 1-2 weeks).
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| Laboratory testing is not required in most cases, as the diarrhea is often self-limited.
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| 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:
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| Stool culture for enteropathogens
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| Shiga toxin assay, to rule out Shiga toxin-producing E. Coli (STEC)
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| Fecal leukocyte or lactoferrin testing
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| Molecular assays targeting common enteropathogens
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| When diarrhea persists for ≥ 14 days, consider testing for parasites with:
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| Stool microscopy for ova, cysts, and parasites (O&P).
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| Stool antigen detection for Giardia spp., Cryptosporidium spp., And Entamoeba histolytica parasites.
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| Modified acid-fast staining of stool for Cyclospora spp.
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| ===Workup===
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| Evaluation of returned travelers:
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| Testing is typically not required as mild or uncomplicated disease is often self-limited or can be treated empirically.2,4
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| Indications for laboratory evaluation include:2,3
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| Diarrhea lasting ≥ 14 days
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| Fever > 101.3 degrees F (38.5 degrees C)
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| Dysentery
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| Cholera-like diarrhea with dehydration
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| 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).
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| Identification of the etiology may help direct pathogen-specific treatment.
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| 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).
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| Testing may include:
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| Stool culture
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| Stool microscopy to examine for ova, cysts, and parasites
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| Blood culture if bacteremia is suspected
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| Fecal leukocytes or fecal lactoferrin test if bacterial infection is suspected
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| Molecular assays targeting multiple pathogens
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| ===Diagnosis===
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| Stool culture for enteropathogens
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| Microscopy and antigen detection to test for parasites
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| Blood tests, including blood culture, if bacteremia is suspected
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| Shiga toxin assay to rule out Shiga toxin-producing Escherichia coli (STEC)
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| Fecal leukocyte or lactoferrin testing
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| Molecular assays for detection of common enteropathogens
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| Blood tests
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| Blood tests may be helpful for patients with persistent, systemic, or severe symptoms and include:2,3
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| Complete blood count (eosinophilia may indicate schistosomiasis, strongyloidiasis, or other helminthic infection)
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| Liver function tests
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| Renal function tests
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| Inflammatory markers (such as erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP])
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| Blood culture if bacteremic salmonellosis (including typhoid fever) is suspected
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| ==Management==
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| Most bacterial and viral cases are self-limited and typically resolve in 2-7 days, though parasitic infection may persist for longer if untreated.
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| The severity of illness determines treatment approach.
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| Mild diarrhea is tolerable, not distressing, and does not interfere with planned activities.
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| Moderate diarrhea is distressing or interferes with planned activities.
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| Severe diarrhea is incapacitating or completely prevents planned activities. All dysentery (grossly bloody stools) is considered severe.
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| Self-treatment is the preferred treatment strategy for many travelers as diarrhea often arises during travel.
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| Provide medications to patients prior to travel.
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| Educate patients about preventive measures.
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| Management strategies:
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| 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.
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| The risk of dehydration is higher in very young children or in adults with chronic medical illness.
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| Oral rehydration may help travelers feel better more quickly.
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| Antimotility therapy can be used when rapid control of symptoms is needed (for example, on a long bus ride without a toilet).
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| Loperamide:
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| Consider as monotherapy in patients with mild (ISTM Strong recommendation, Moderate-level evidence) or moderate (ISTM Strong recommendation, High-level evidence) traveler's diarrhea.
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| Loperamide ay be used as adjunctive therapy with antibiotics in patients with moderate-to-severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence).
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| Dosing by age:
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| 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).
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| 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).
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| 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).
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| Do not use loperamide as monotherapy in patients with bloody diarrhea and fever.
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| Bismuth subsalicylate:
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| Consider bismuth subsalicylate in patients with mild traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence).
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| It may reduce nausea.
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| Dosing in adults and children ≥ 12 years old:
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| 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).
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| 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).
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| Bismuth subsalicylate is not recommended in children < 3 years old and typically not used in children < 12 years old.
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| Antibiotics are recommended for patients with moderate-to-severe diarrhea.
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| Antibiotics may reduce the duration of illness, but may carry an increased risk of adverse events.
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| International Society of Travel Medicine recommendations for antibiotic use in traveler's diarrhea:
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| Antibiotics are not recommended for mild traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence).
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| Consider antibiotic therapy for moderate traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence). Options include:
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| Azithromycin (ISTM Strong recommendation, High-level evidence)
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| Fluoroquinolones (ISTM Strong recommendation, Moderate-level evidence) with qualifications due to the:
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| Emergence of resistance to this drug class, especially in Southeast Asia
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| Potential for adverse dysbiotic and musculoskeletal events
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| Rifaximin (ISTM Weak recommendation, Moderate-level evidence), but caution is suggested when considering rifaximin in regions with a high risk of invasive pathogens
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| Antibiotics are recommended for severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence). Options include:
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| Azithromycin (preferred) (ISTM Strong recommendation, Moderate-level evidence)
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| Fluoroquinolones or rifaximin for severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence)
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| Single-dose regimens are recommended for moderate or severe traveler's diarrhea (ISTM Strong recommendation, High-level evidence).
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| Antibiotics and antimotility agents should be avoided in cases of known or suspected infection with Shiga toxin-producing organisms.
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| 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.
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| Preferred options for giardiasis include:
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| 5-nitroimidazoles, such as:
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| Tinidazole 2 g orally single dose (50 mg/kg single dose in children)
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| Metronidazole 250 mg orally 3 times daily (15 mg/kg/day in 3 divided doses for children) for 5-7 days
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| 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)
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| See Giardiasis for additional information.
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| Cryptosporidiosis may be treated with nitazoxanide.
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| Cyclosporiasis may be treated with trimethoprim-sulfamethoxazole.
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| Amebiasis may be treated with metronidazole or tinidazole, followed by luminal agent such as paromomycin or iodoquinol.
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| ==Disposition==
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| Fluoroquinolones
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| International Society of Travel Medicine (ISTM) recommendations suggest fluoroquinolones may be used to treat:5
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| Moderate traveler's diarrhea (ISTM Strong recommendation, Moderate-level evidence), with qualifications due to the:
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| Emergence of resistance to this drug class, especially in Southeast Asia
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| Potential for adverse dysbiotic and musculoskeletal events
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| Severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence)
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| Avoid fluoroquinolones in cases of suspected Shiga toxin-producing Escherichia coli (STEC), due to the potential for increased risk of complications.4
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| Dosing:1,2,3,5
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| 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)
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| Ciprofloxacin:
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| 750 mg orally as single dose (continue daily dosing for up to 3 days if symptoms do not resolve after 24 hours) OR
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| 500 mg orally twice daily for 3 days
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| 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)
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| Norfloxacin 400 mg orally once daily (not available in the United States)
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| Fluoroquinolones may be associated with abdominal discomfort, nausea, insomnia, or irritability.4
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| Considerations in special populations:4
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| There have been concerns about transient musculoskeletal effects in children, but ciprofloxacin is considered safe for pediatric patients, particularly for short-course treatment.
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| Use is not routinely advised during pregnancy.
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| STUDY SUMMARY
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| fluoroquinolones appear to be effective in patients with traveler's diarrhea
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| DynaMed Level
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| 2
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| RANDOMIZED TRIAL: Antimicrob Agents Chemother 1992 Jan;36(1):87
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| Details
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| Resistance to fluoroquinolones
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| Increasing rates of resistance to fluoroquinolones have been found among causative organisms of traveler's diarrhea.1,5
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| Impacted pathogens include Campylobacter, Shigella and Salmonella species.
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| Fluoroquinolone resistance is particularly widespread in Southeast and South Asia.
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| STUDY SUMMARY
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| resistance of Campylobacter to fluoroquinolones may be increasing
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| COHORT STUDY: N Engl J Med 1999 May 20;340(20):1525
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| COHORT STUDY: Emerg Infect Dis 2002 Dec;8(12):1501
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| COHORT STUDY: Emerg Infect Dis 2003 Feb;9(2):267
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| COHORT STUDY: Clin Infect Dis 1998 Feb;26(2):341
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| COHORT STUDY: Am J Trop Med Hyg 2002 Nov;67(5):533
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| Details
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| 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).
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| Azithromycin
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| International Society of Travel Medicine (ISTM) recommendations for azithromycin:5
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| Azithromycin may be used to treat moderate traveler's diarrhea (ISTM Strong recommendation, High-level evidence).
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| It is the preferred treatment for severe traveler's diarrhea (including dysentery or febrile diarrhea) (ISTM Strong recommendation, Moderate-level evidence).
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| 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.
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| Azithromycin is effective against a broad range of pathogens that cause traveler's diarrhea, including Campylobacter infection.2,4
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| Dosage:1,5
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| Adult dosing:
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| 1,000 mg orally once (if symptoms are not resolved after 24 hours, continue daily dosing for up to 3 days)
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| 500 mg orally once daily for 3 days
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| Dosing in children: 10 mg/kg orally once daily for 3 days
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| Azithromycin is considered safe for children and pregnant persons.4
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| It may be associated with pruritus or candida vaginitis.4
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| Efficacy:
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| Azithromycin 500 mg appears to have similar clinical efficacy compared to ciprofloxacin 500 mg in patients with traveler's diarrhea
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| DynaMed Level
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| 2
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| .
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| Single dose azithromycin appears at least as effective as single dose levofloxacin for traveler's diarrhea
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| DynaMed Level
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| 2
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| .
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| Azithromycin 1,000 mg appears to have similar efficacy compared to levofloxacin 500 mg in adults with traveler's diarrhea receiving loperamide
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| DynaMed Level
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| 2
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| .
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| 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
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| DynaMed Level
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| 2
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| .
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| See Comparative efficacy of antibiotics for the details of each study.
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| Rifaximin
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| International Society of Travel Medicine (ISTM) recommends rifaximin may be used for treatment of:5
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| Moderate traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence), but suggest caution when considering rifaximin in regions with high risk of invasive pathogens
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| Severe, nondysenteric traveler's diarrhea (ISTM Weak recommendation, Moderate-level evidence)
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| Rifaximin is a poorly absorbed, gut-selective antibiotic.2,5
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| Rifaximin (Xifaxan) is FDA approved for treatment of patients ≥ 12 years old with traveler's diarrhea caused by noninvasive E. coli.
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| Dose is 200 mg orally three times daily for 3 days.
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| Adverse effects include headache.
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| Reference - FDA DailyMed 2020 Oct 30
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| STUDY SUMMARY
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| rifaximin may reduce duration of traveler's diarrhea in adults
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| DynaMed Level
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| 2
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| RANDOMIZED TRIAL: Am J Gastroenterol 2003 May;98(5):1073
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| Details
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| Rifamycin
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| Rifamycin (Aemcolo) is FDA approved for treatment of traveler’s diarrhea caused by noninvasive Escherichia coli.
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| 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.
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| Dosing and administration:
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| Dosing is 388 mg orally twice daily (in the morning and evening) for 3 days.
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| Take each dose with 6-8 ounces of liquid.
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| Do not take with alcohol.
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| Adverse effects include headache and constipation.
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| Reference - FDA DailyMed 2020 Feb 14
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| Rifamycin may be considered as an alternative to rifaximin.1
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| ==See Also== | | ==See Also== |
