AN ONGOING CE PROGRAM
OF THE UNIVERSITY OF CONNECTICUT
SCHOOL OF PHARMACY
AND DRUG TOPICS
2 EARN CE CREDIT
CPE FOR THIS ACTIVITY AT
CREDITS WWW.DRUGTOPICS.COM
EDUCATIONAL OBJECTIVES
GOAL: The goal of this activity is to review the various risk
The Rundown:
Management of
factors, etiologies, and treatments of diarrhea as well
as the pharmacist’s role in its management.
Diarrhea
of diarrhea, including the mechanism of
action, indications, side effects, onset of
effect, duration of therapy, and clinical usage
considerations for each agent
> Outline the pharmacist’s role in providing
recommendations to treat diarrhea and
referral to a physician for inadequate response
to OTC therapies
Alexa A. Carlson, PharmD, BCPS
After participating in this activity, ASSISTANT CLINICAL PROFESSOR, DEPARTMENT OF PHARMACY AND HEALTH SYSTEMS SCIENCES, NORTHEASTERN UNIVERSITY,
pharmacy technicians will be able to: SCHOOL OF PHARMACY, BOSTON, MA
> Recall the basic definition of diarrhea
> Recall the risk factors for diarrhea Tayla N. Rose, PharmD
> List available OTC and prescription drug ASSISTANT CLINICAL PROFESSOR, DEPARTMENT OF PHARMACY AND HEALTH SYSTEMS SCIENCES, NORTHEASTERN UNIVERSITY,
therapies for diarrhea SCHOOL OF PHARMACY, BOSTON, MA
> Recognize when to refer patients to the
pharmacist for recommendations on diarrhea
management
Alycia Gelinas
STUDENT PHARMACIST, CLASS OF 2016, NORTHEASTERN UNIVERSITY, SCHOOL OF PHARMACY, BOSTON, MA
and click on the “Take a Quiz” link. This will direct you
to the UConn/Drug Topics website, where you will click Faculty Disclosure: Dr. Carlson, Dr. Rose, and Ms. Gelinas have no actual or potential conflicts of interest associ-
on the Online CE Center. Use your NABP E-Profile ID and ated with this article.
the session code: 16DT29-YFJ22 for pharma- Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion of
cists or the session code: 16DT29-XFT88 for
pharmacy technicians to access the online quiz
unlabeled/unapproved use of drugs in the United States and will be noted if it occurs. The content and views
and evaluation. First-time users must pre-register in presented in this educational program are those of the faculty and do not necessarily represent those of Drug
the Online CE Center. Test results will be displayed Topics or University of Connecticut School of Pharmacy. Please refer to the official information for each product
immediately and your participation will be recorded for discussion of approved indications, contraindications, and warnings. Please refer to the official prescribing
with CPE Monitor within 72 hours of completing the information for each product for discussion of approved indications, contraindications, and warnings.
requirements.
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DRUGTOPICS.COM | JUNE 2016 | DrugTopics 55
CONTINUING EDUCATION
M A NAG E M E N T OF AC U T E A N D CH RON IC DI A R R H E A
Introduction TABLE 1
Diarrhea affects nearly all patients at Classification of Diarrhea
some point in their lives. Although diar-
FREQUENCY CLASSIFICATION
rhea is commonly categorized as merely a
bothersome symptom in the United States
(US), the consequences of diarrhea can be Acute ≤14 days in duration
fatal if not properly managed. Each year,
Persistent >14 days in duration
an estimated 2 billion cases of diarrheal
disease and 2.5 million deaths due to Chronic >30 days in duration
diarrhea-related illness occur worldwide.1,2
Diarrhea, in its most basic definition, is MECHANISTIC CLASSIFICATION
a variation from normal bowel movements
with stools of increased frequency and/or Occurs when a substance either decreases absorption or increases secretion of
decreased consistency. Normal bowel hab- large quantities of water and electrolytes in the gastrointestinal tract
its vary among individuals, with frequency Secretory Leads to large stool volume (>1 L/d)
ranging from three times per week to three Fasting does not alter stool volume
May be caused by bacterial toxins, laxatives, or excess bile salts
times per day, and these variations must
be considered when clinicians are evaluat- Occurs when a poorly absorbed substance retains intestinal fluids and leads to a
ing patients and recommending treatments flux of water and electrolytes into the lumen as the gut adjusts to the osmolality
for symptom management. To help guide of the plasma
Osmotic
treatment recommendations, diarrhea can Unlike other mechanisms, fasting causes diarrhea to stop
be classified by suspected or proven etiol- May be caused by lactose intolerance or ingestion of magnesium-containing
antacids or poorly soluble carbohydrates (lactulose)
ogy (infectious or noninfectious), duration,
and pathophysiologic mechanism. Diarrhea Occurs when an inflammatory process in the GI tract causes discharge of
is defined as acute, persistent, or chronic mucous, serum proteins, and blood into the gut, and discharged substances are
based on the duration of symptoms, and Exudative excreted in the stool
the pathophysiologic mechanism may fall Absorption, secretory, or motility functions are altered to accommodate
large stool volume
into one or more of the following clinical
groups: secretory, osmotic, exudative, or Occurs when altered intestinal motility leads to reduction in contact time of
motor (Table 1).2-4 chyme (semifluid combination of gastric fluids and partially digested food) in
Treatment recommendations vary the small intestine; premature emptying of the colon; and bacterial overgrowth.
greatly depending on the etiology, dura- Diarrhea may also be caused by increased contact time, which leads to
Motor overgrowth of fecal bacteria and rapid dumping of chyme into the colon that is
tion, and pathophysiologic mechanism of unable to absorb water
diarrhea; therefore, an attempt should be May occur with bypass surgery, intestinal resection, or administration of
made to classify a diarrheal episode upon metoclopramide
presentation. Pharmacists and pharmacy Source: Refs 2,4
technicians play an integral role in the man-
agement of diarrhea through self-treatment an). Infectious etiologies may be ruled out propriate solutions by mouth to prevent
recommendations or referrals for medical with a negative stool culture and testing or correct dehydration related to diarrhea.
evaluation. Thus, it is critical for pharma- for ova and parasites.5 Noninfectious diar- ORT solutions recommended by the WHO
cists and technicians to be familiar with rhea can occur acutely due to medication contain the following per 1 L of solution:
the various classifications of diarrhea and and food intolerance or chronically due to 2.6 g sodium chloride, 2.9 g trisodium ci-
the prescription and over-the-counter (OTC) primary gastrointestinal (GI) disease, such trate, 1.5 g potassium chloride, and 13.5 g
products available for treatment and symp- as inflammatory bowel disease. glucose.6 ORT has been found to be a
tom management. This review will focus on cost-effective means of managing acute
treatment and management of diarrhea in Hydration and diet management diarrhea and reducing hospitalizations.2
immunocompetent adults. The main component of treatment for ORT solutions such as Pedialyte are not
acute noninfectious diarrhea is hydration interchangeable with sports drinks and
Noninfectious diarrhea therapy to maintain water and electrolyte more closely resemble the WHO ORT rec-
Diarrhea is classified as noninfectious balances despite the loss of important ommendations for replenishment during
when symptoms worsen or become chron- salts in the stool. The World Health Or- diarrheal illness. However, in otherwise
ic in the absence of an identifiable infec- ganization (WHO) defines oral rehydration healthy patients who present without
tious organism (virus, bacterium, protozo- therapy (ORT) as the administration of ap- dehydration, adequate fluid intake may
be achieved with consumption of broths, complete relief of acute nonspecific diar- intestine, and is used as an energy source
soups, diluted fruit juices, soft drinks, and rhea and gas-related symptoms compared for bacteria residing in the intestinal tract.
salted crackers.7 with either agent administered alone.13 In addition to producing gas, undigested
Specific dietary recommendations out- Bismuth subsalicylate (Pepto-Bismol) is lactose creates an osmotic pull in the GI
side of ORT are not well supported in the an alternative option for the symptomatic tract that leads to water retention in the
clinical literature. In fact, abstaining from treatment of diarrhea in adults.5 Bismuth bowel and subsequent diarrhea.16 Patients
food consumption during the occurrence of subsalicylate has demonstrated antisecre- who experience gas and diarrhea after
diarrheal symptoms appears to have little tory, anti-inflammatory, and antibacterial consumption of lactose-containing prod-
positive effect on outcomes.8 ORT with effects.4 Bismuth subsalicylate is adminis- ucts such as milk, ice cream, or cheese
early refeeding is the preferred treatment tered in doses of 525 mg (two 262 mg tab- may self-administer lactase tablets (eg,
for dehydration to reduce the duration of lets) every 30 to 60 minutes or 1,050 mg Lactaid) before ingesting the aforemen-
illness and improve nutritional outcomes.9 (four 262 mg tablets) every 60 minutes as tioned dairy products. However, as with
Adequate nutrition is also necessary to en- needed for up to two days, with a maximum all food intolerances, avoidance of the
able renewal of cells in the intestinal lining dose of approximately 4,200 mg/24 h. causative food products is highly recom-
called enterocytes.10 An initial response can be seen within mended.
TABLE 2
New Agents for the Treatment of IBS-D
AMERICAN COLLEGE OF
MECHANISM
DRUG COMMON ADVERSE DRUG-DRUG GASTROENTEROLOGY COST (AWP)
OF ACTION DOSING REACTIONS INTERACTIONS RECOMMENDATIONS
Eluxadoline Mu-opioid 100 mg twice Abdominal pain Cyclosporine increases Approved after guideline $1152.00 (30-day
receptor agonist daily with food Constipation exposure to eluxadoline monograph issued supply)
Nausea Eluxadoline may
increase exposure to
rosuvastatin
Strong CYP inhibitors
may increase exposure
to eluxadoline
Rifaximin Rifamycin 550 mg Increased ALT Cyclosporine increases Weak recommendation for $1539.31 (14-day
antibacterial three times Nausea exposure to rifaximin use to decrease bloating supply)
daily for 14 and other symptoms in
days; maybe IBS-D
repeated for
2 additional
courses
Abbreviations: AWP, average wholesale price; ALT, alanine aminotransferase. Source: Refs 22,26-28
determine the risk versus benefit for the 40% of patients with IBS may be charac- sistency of stools.23 Furthermore, eluxado-
medication’s therapeutic effects and the terized as IBS-D.19 line has shown benefit in patients whose
side effect of diarrhea. In patients taking Loperamide has demonstrated efficacy symptoms are not adequately relieved with
magnesium-containing antacids, antacids in decreasing fecal urgency and frequency loperamide.23,24 Common adverse effects
with calcium carbonate may be recom- of stools as well as increasing the number associated with this agent include nausea
mended as an alternative.17 Any unap- of formed stools in patients with IBS-D.23 and constipation (Table 2).22,23,26-28
proved herbals or supplements such as St. However, it does not provide relief from Rifaximin is a rifamycin antibiotic simi-
John’s wort should be stopped if they are other symptoms such as pain and bloat- lar to rifampin that is not significantly ab-
suspected of being the causative agent. ing. Current American College of Gastroen- sorbed into systemic circulation.24 Its effi-
terology treatment guidelines do not rec- cacy in IBS-D is attributed to alterations
Irritable bowel syndrome-diarrhea ommend the use of loperamide for IBS-D in GI flora.23 Rifaximin has been shown to
Irritable bowel syndrome (IBS) is a relaps- because of lack of strong evidence.22 decrease many symptoms of IBS-D, includ-
ing and remitting disorder of the bowel as- Tricyclic antidepressants may be useful ing abdominal discomfort/pain, unformed
sociated with abnormal defecation and ab- in relieving symptoms of IBS-D because of stools, and bloating.23,24 Patients whose
dominal discomfort/pain affecting 11.8% their ability to slow transit through the GI condition relapsed after an initial course
of the US population.19,20 It is thought to tract.23 Guidelines include a weak recom- of rifaximin achieved statistically significant
be more common in younger individuals mendation for the use of tricyclic antide- benefits with up to two additional cours-
and in women.20,21 To receive a diagno- pressants but recognize that limited evi- es.24 Rifaximin is generally well tolerated;
sis of IBS, patients must be symptomatic dence is available and that patients may the most common adverse effects include
for at least six months. Diagnostic symp- find the anticholinergic adverse effects GI and upper respiratory symptoms.23,24
toms include abdominal discomfort/pain intolerable.22 Current guidelines include a weak recom-
that has occurred on at least three days Eluxadoline is a mu-opioid receptor mendation for the use of rifaximin for the
per month for the past three months and agonist and delta-opioid antagonist that relief of bloating and other symptoms of
that meets at least two of the following reduces the symptoms of IBS-D by slowing IBS-D.22
stipulations: is accompanied by changes motility and relieving pain in the GI tract.24 Serotonergic antagonists are believed
in consistency of stool, is accompanied Eluxadoline became available in December to provide benefit in IBS-D through modu-
by increased/decreased defecation, or is 2015 and is classified as a Schedule IV lation of secretion and motility in the GI
alleviated upon defecation.22 Once diag- controlled substance by the Drug Enforce- tract.23 Alosetron, which was removed
nosed, cases may be further classified ment Administration.25 Decreases in ab- from the US market in 2001 because of
into diarrhea-predominant IBS (IBS-D), dominal pain, stool frequency, and urgen- a risk of ischemic colitis, has been avail-
constipation-predominant IBS (IBS-C), or cy have been associated with eluxadoline able since 2002 with access currently
mixed IBS (IBS-M).19,21 It is estimated that therapy in conjunction with improved con- restricted by a Risk Evaluation and Mitiga-
and alcohol. The use of alcohol while tak- common side effects associated with fidax- of food or beverages contaminated with
ing metronidazole can lead to a reaction omicin include GI adverse effects such as pathogenic bacteria.47 Commonly impli-
similar to that seen with disulfiram, which nausea and diarrhea. Because of its high cated food carriers include salads, raw
may include nausea, vomiting, headache, cost, fidaxomicin is not used as a first-line vegetables, unpeeled fruits, and seafood
and abdominal cramps. As such, patients agent. In studies comparing fidaxomicin or meat products that are not thoroughly
should abstain from alcohol while they are with vancomycin, fidaxomicin was found cooked.43 Activities such as hiking and
taking metronidazole and for three days to be noninferior to vancomycin for clinical camping are particularly risky because of
after treatment. Vancomycin is a bacteri- cure rates but was associated with signifi- the limited ability to properly clean and
cidal glycopeptide antibiotic that works by cantly lower rates of recurrence.42 cook foods.43 Travelers should be aware of
inhibiting the formation of the bacterial cell The first recurrence of CDAD can be the possibility of contracting TD based on
wall.39 Because this agent has minimal managed with the same preferred therapy, the region to which they will be venturing.
systemic absorption, orally administered whereas a second recurrence may be man- Mexico, Central and South America, Africa,
vancomycin is indicated only for the man- aged with pulsed or tapered dose vanco- most of Asia, and the Middle East are con-
agement of CDAD and enterocolitis second- mycin. Alternative management strategies, sidered to be the highest risk.44 Conversely,
ary to Staphylococcus aureus, and routine including stool transplants, may also be the lowest risk regions are Australia, New
monitoring of vancomycin levels is unnec- considered at this point. Zealand, North and West Europe, Canada,
essary. The most common adverse effects Traveler’s diarrhea. TD affects individu- and Japan.45 Timing of travel is an important
of vancomycin are nausea, abdominal pain, als who live in developed countries and consideration, as most cases of TD occur
flatulence, diarrhea, and vomiting. Vanco- travel to less developed or more tropical during hot and rainy seasons.43
mycin-resistant Enterococcus is a concern areas of the world.43 Afflicted patients ex-
with overuse of oral vancomycin therapy.
Zar et al completed a prospective, ran-
perience at least three loose stools within
a one-day period accompanied by at least
Antibiotics are
domized, double-blind, placebo-controlled
trial comparing metronidazole 250 mg by
one of the following symptoms: elevated
temperature, cramping or pain in the abdo-
the mainstay of
mouth four times daily to vancomycin 125 men, urgency to defecate, stools containing pharmacologic therapy
mg by mouth four times daily for 10 days in mucus or blood, nausea, or vomiting.43,44
patients stratified by CDAD disease sever- It is estimated that one in two people who for TD and should be
ity.40 In patients with mild disease, 90% of
patients taking metronidazole (37/41) and
travel to developing areas will experience di-
arrhea.45 TD develops within the first seven
initiated after a patient
98% of those taking vancomycin (39/40) days of the trip and often runs its course in passes three or more
achieved clinical cure (P = 0.36). For those seven days or fewer without medication.43,44
with severe disease, a significant differ- However, one in five patients with TD may unformed stools in 24
ence was found between the two groups, experience symptoms significant enough
with 76% (29/38) achieving clinical cure in to limit activities, and one in 100 patients hours.”
the metronidazole group compared to 97% may experience severe illness requiring
(30/31) in the vancomycin group (P = 0.02), hospital admission.43 Patients may consult a pharmacist re-
suggesting the benefit of preferential use Bacteria cause eight of 10 cases of TD; garding strategies to prevent TD before trav-
of vancomycin in this population. No sig- therefore, bacterial pathogens will be the el. Antibiotic prophylaxis is very effective but
nificant difference was found in the rate of focus of this review.43,46 The most frequently is generally not recommended because of
relapse between the two groups (14% in implicated bacteria are ETEC, followed by increased risk of adverse effects and anti-
the metronidazole group; 7% in the vanco- other common pathogens such as Shigella biotic resistance.44 Furthermore, changes to
mycin group; P = 0.27). This led the IDSA to species, Campylobacter, Aeromonas spe- normal GI flora precipitated by antibiotic use
recommend that mild to moderate disease cies, Salmonella species, and Plesiomo- may in fact increase a patient’s susceptibil-
should be managed with oral metronidazole nas species, with prevalence varying by ity to infection by more virulent pathogens.44
therapy, whereas vancomycin should be location.43,44,46 Other important causative Additionally, antibiotic prophylaxis may lead
used for severe CDAD (Table 3).35-37 agents include parasites such as Giardia patients to have a false sense of protection
Fidaxomicin is a macrocyclic antibiotic (comprising approximately 10% of TD cases) and be less cautious when selecting food
indicated for the management of CDAD- and viruses such as norovirus and rotavi- and beverages.46
associated diarrhea in patients at least 18 rus (comprising <10% of TD cases).43,44,46 Bismuth subsalicylate has been shown
years of age. This agent maintains bacte- Information about the management of viral to decrease the risk of TD by half when
ricidal activity by inhibiting RNA synthesis. diarrhea can be found in the “infectious di- used prophylactically.44 However, patients
The FDA-approved dose is 200 mg by arrhea” section of this article. must take two tablets four times daily, and
mouth twice daily for 10 days.41 The most TD is transmitted by the consumption pill burden limits the usefulness of this regi-
men. Patients should be counseled that the sources.47 The most common of these in- because of an increased risk of complica-
most effective strategies for preventing TD fectious etiologies include Salmonella spe- tions resulting in hospitalization or death.
are proper hand hygiene and selection of cies, Shigella species, S aureus, Campylo- Pregnant women, patients taking immuno-
foods and beverages. Before eating, pa- bacter species, and norovirus; Salmonella suppressive medications, and those with
tients should clean their hands thoroughly species are associated with the highest immunocompromising diseases should be
with soap and water or alcohol-containing annual rates of illnesses, hospitalizations, treated under the care of a provider. Pa-
sanitizers if clean water is not available.44 and deaths.48 Symptoms of foodborne ill- tients who report severe pain in the abdo-
Travelers should seek fruits and vegeta- ness occur within hours to days of infec- men and those who observe pus or blood
bles that can be peeled or that have been tion depending on the causative organism in the stool should be referred to rule out
rinsed with clean water. They should only and are short in duration.30 Foods com- more serious illnesses. Technicians may
eat meals that have been recently cooked. monly associated with foodborne illnesses play a role in collecting information about
Beverages should be bottled if possible or include meats, poultry, water, unpasteur- patient symptoms and severity in prepara-
boiled before consumption if not bottled.45 ized dairy products, and vegetables. An tion for referral to the pharmacist.
If a patient does contract TD, the first assessment of foodborne illness causes Those patients who are eligible for
step is to adequately replace fluids and in the US from 1998 to 2008 found that self-care with OTC products should be
electrolytes.44 Parents traveling with young norovirus was associated with the most counseled that use of these agents is not
children should be counseled to carry ORT. outbreaks of foodborne illnesses. Produce recommended beyond 48 hours after the
ORT must be prepared by combining the commodities, including fruits, vegetables, onset of acute diarrhea symptoms, regard-
contents of the packet with a specified and nuts, accounted for many of the ill- less of when OTC products are initiated.17
amount of sterile water.44 Many patients, nesses (46%), and leafy vegetables ac- Chronic and persistent diarrhea should be
especially children, may find the salty taste counted for more illnesses than any other further evaluated by a provider before con-
of ORT to be unpleasant; however, ORT commodity (22%). Poultry-based infections tinued use of self-care interventions.
should be replaced with more palatable (19%) were primarily caused by Listeria
sports drinks only in cases of mild diarrhea. monocytogenes or Salmonella species.49 Conclusion
Beverages with high sugar content such as Preventive strategies include avoidance Diarrhea is a common complaint with a
fruit juice and cola have the potential to ex- of undercooked seafood or meat, preven- higher incidence of morbidity and mortal-
acerbate diarrhea through osmotic effects tion of cross-contamination, and avoidance ity in patients at the extremes of age and
and should therefore be avoided. Antibi- of unpasteurized dairy products.3 Treatment in immunosuppressed populations. Hydra-
otics are the mainstay of pharmacologic strategies include supportive care with flu- tion is the primary treatment modality for
therapy for TD and should be initiated after ids and electrolytes. Foodborne illnesses both noninfectious and infectious diarrhea.
a patient passes three or more unformed caused by Bacillus cereus, Clostridium per- Noninfectious diarrhea may be caused by
stools in a 24-hour period.46 Fluoroquino- fringens, and S aureus do not benefit from food intolerances, in which case patients
lones, specifically levofloxacin and cipro- antimicrobial therapy management; the should be counseled to avoid the offend-
floxacin, are the antibiotics of choice, and management of other infectious causes of ing foods, or by IBS-D, for which newer
a one-day course of these agents is usually foodborne illnesses has been discussed in treatment modalities may be employed.
sufficient.44 In areas where resistance to previous sections. Other management options for noninfec-
fluoroquinolones is increasing among TD tious diarrhea include bismuth subsalicy-
pathogens, azithromycin 500 mg may be The pharmacist’s role and self-care late and loperamide. Infectious diarrhea
used for one to three days. Rifaximin is exclusions may be caused by bacterial, viral, or pro-
not approved for empiric therapy but may When assessing a patient with diar- tozoal sources; the management of these
be used when the causative pathogen is rhea, pharmacists should first determine cases depends on the underlying cause
known to be noninvasive E coli. Antimotility whether a patient is in need of medical of infection. Preventive therapy for infec-
agents such as loperamide are generally evaluation, such as those patients at risk tious diarrhea is focused on vaccinations
considered safe and effective when used for dehydration and other complications. when appropriate, proper hand hygiene,
in conjunction with antibiotics to provide Patients who are at high risk for dehydra- antibiotic stewardship, and proper food
additional symptom relief.44 tion include those with diarrhea lasting preparation to prevent cross-contamina-
more than two days, diarrhea occurring tion. Because loperamide monotherapy
Foodborne illness at least six times per day, those who are has the potential to worsen disease and
There are approximately 9.4 million epi- experiencing frequent vomiting in addition cause complications, this treatment option
sodes, 56,000 hospitalizations, and more to diarrhea, and those with fever (temper- should be avoided in most cases of infec-
than 1000 deaths due to foodborne ill- ature of at least 101.3°F/38.5°C).50 Indi- tious diarrhea.
nesses each year in the US. These may viduals who are less than two years old References are available online at
be caused by bacterial, parasitic, or viral or older than 65 years should be referred www.drugtopics.com/cpe. •
For Pharmacists
1. Which of the following medications for IBS-D 4. Which of the following bacteria are most b. Cephalosporins
is only available through a Risk Evaluation and commonly implicated in traveler’s diarrhea? c. Amoxicillin
Mitigation Strategy program? a. Enterotoxigenic Escherichia coli d. All of the above
a. Alosetron b. Salmonella species
b. Eluxadoline c. Shigella species 8. In a patient with mild CDAD, which of the
c. Loperamide d. Campylobacter species following agents is considered first-line therapy?
d. Rifaximin a. Metronidazole
5. Which of the following is a cause of infectious b. Vancomycin
2. Which of the following medications for IBS-D is diarrhea? c. Rifaximin
a schedule IV controlled substance? a. Bacteria d. Fidaxomicin
a. Alosetron b. Viruses
b. Eluxadoline c. Protozoa 9. Based on epidemiologic studies, which of the
c. Loperamide d. All of the above following food substances was most commonly
d. Rifaximin associated with foodborne illnesses?
6. In the management of noninfectious diarrhea, a. Fruits
3. Which of the following patients should be which of the following OTC agents is associated b. Poutry
referred for medical evaluation? with tinnitus? c. Leafy vegetables
a. 45-year-old man with a 36-hour history of diarrhea a. Bismuth subsalicylate d. Shellfish
and a temperature of 101°F b. Loperamide
b. 18-year-old woman with a three-day history of c. Pedialyte 10. Which of the following is the primary cause of
diarrhea and a temperature of 99.6°F d. Omeprazole gastroenteritis in the United States?
c. 12-year-old boy with four loose stools occurring in
7. Which of the following antibiotics is commonly a. Rotavirus
the past 24 hours and a temperature of 100.4°F
associated with causing Clostridium difficile b. Norovirus
d. 56-year-old man with three loose stools and one
associated diarrhea (CDAD)? c. Salmonella species
episode of vomiting in the past 18 hours and a
d. Escherichia coli
temperature of 98.5°F a. Fluoroquinolones
References
1. Kosek M, Bern C, Guerrant RL. The global burden of di- 23. Lacy BE. Diagnosis and treatment of diarrhea-predominant [erratum in N Engl J Med. 2013;368:2242]. N Engl J Med.
arrhoeal disease, as estimated from studies published irritable bowel syndrome. Int J Gen Med. 2016;9:7-17. 2013;368:1817-1825.
between 1992 and 2000. Bull World Health Organ.
24. Rivkin A, Rybalov S. Update on the management of diar- 46. DuPont HL, Ericsson CD. Prevention and treatment of trav-
2003;81:197-204.
rhea-predominant irritable bowel syndrome: focus on rifaxi- eler’s diarrhea. N Engl J Med. 1993;328:1821-1827.
2. Farthing M, Salam MA, Lindberg G, et al; WGO. Acute di- min and eluxadoline. Pharmacotherapy. 2016;36:300-316.
arrhea in adults and children: a global perspective. J Clin 47. Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness
25. Drug Scheduling. United States Drug Enforcement Agency. acquired in the United States—major pathogens. Emerg
Gastroenterol. 2013;47:12-20.
www.dea.gov/druginfo/ds.shtml. Accessed April 21, 2016. Infect Dis. 2011;17:7-15.
3. Guerrant RL, Van Gilder T, Steiner TS, et al; Infectious
26. Viberzi (eluxadoline) prescribing information. Parsippany, NJ: 48. Estimates of Foodborne Illness in the United States. Cen-
Diseases Society of America. Practice guidelines for
Actavis Pharma; 2015. ters for Disease Control and Prevention. Updated January
the management of infectious diarrhea. Clin Infect Dis.
2001;32:331-351. 27. Xifaxan (rifaximin) prescribing information. Bridgewater, NJ: 8, 2014. www.cdc.gov/foodborneburden. Accessed April
Salix Pharmaceuticals; 2015. 21, 2016.
4. Fabel PH, Shealy KM. Diarrhea, constipation, and irritable
bowel syndrome. In: DiPiro JT, Talbert RL, Yee GC, Matzke 28. Red Book Online [data base online]. Greewood Village, CO: 49. Painter JA, Hoekstra RM, Ayers T, et al. Attribution of
GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Patho- Truven Health Analytics. http://www.micromedexsolutions. foodborne illnesses, hospitalizations, and deaths to food
physiologic Approach. 9th ed. New York, NY: McGraw-Hill; com/. Accessed April 10, 2016. commodities by using outbreak data, United States, 1998-
2014:531-548. 2008. Emerg Infect Dis. 2013;19:407-415.
29. Min YW, Rhee PL. The clinical potential of ramosetron in the
5. Barr W, Smith A. Acute diarrhea. Am Fam Physician. treatment of irritable bowel syndrome with diarrhea (IBS-D). 50. Walker PC. Diarrhea. In: Berardi RR, ed. Handbook of Non-
2014;89:180-189. Therap Adv Gastroenterol. 2015;8:136-142. prescription Drugs: An Interactive Approach to Self-Care.
16th ed. Washington DC: American Pharmacists Associa-
6. Oral rehydration therapy and oral rehydration salts. 30. Martin S, Jung R. Gastrointestinal infections and enterotoxi- tion; 2009:289-308.
In: Oral Rehydration Salts: Production of the New ORS. genic poisonings. In: DiPiro JT, Talbert RL, Yee GC, Matzke
Geneva, Switzerland: World Health Organization and UNI- GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Patho-
CEF; 2006:11-12. physiologic Approach. 9th ed. New York, NY: McGraw-Hill;
2014:1807-1820.
7. DuPont HL. Guidelines on acute infectious diarrhea in
adults. The Practice Parameters Committee of the Ameri- 31. DuPont HL. Acute infectious diarrhea in immunocompetent
can College of Gastroenterology. Am J Gastroenterol. adults. N Engl J Med. 2014;370:1532-1540.
1997;92:1962-1975. 32. Charles MD, Holman RC, Curns AT, Parashar UD, Glass RI,
8. De Bruyn G. Diarrhea in adults (acute). Am Fam Physician. Bresee JS. Hospitalizations associated with rotavirus gas-
2008;78:503-504. troenteritis in the United States, 1993-2002. Pediatr Infect
Dis J. 2006;25:489-493.
9. Gadewar S, Fasano A. Current concepts in the evaluation,
diagnosis and management of acute infectious diarrhea. 33. Rotavirus Vaccine Information Statement. Centers for Dis-
Curr Opin Pharmacol. 2005;5:559-565. ease Control and Prevention. Updated April 16, 2015. www.
cdc.gov/vaccines/hcp/vis/vis-statements/rotavirus.html.
10. Duggan C, Santosham M, Glass RI. The management of
Accessed April 21, 2016.
acute diarrhea in children: oral rehydration, maintenance,
and nutritional therapy. Centers for Disease Control and 34. Bok K, Green KY. Norovirus gastroenteritis in immunocom-
Prevention. MMWR Recomm Rep. 1992;41:1-20. promised patients. N Engl J Med. 2012;367:2126-2132.
11. Heel RC, Brogden RN, Speight TM, Avery GS. Loperamide: 35. Leffler DA, Lamont JT. Clostridium difficile infection. N Engl
a review of its pharmacological properties and therapeutic J Med. 2015;372:539-548.
efficacy in diarrhoea. Drugs. 1978;15:33-52. 36. Cohen SH, Gerding DN, Johnson S, et al; Society for Health-
12. Imodium A-D (loperamide) package insert. Fort Washington, care Epidemiology of America; Infectious Diseases Society
PA: Johnson & Johnson Consumer Inc, McNeil Consumer of America. Clinical practice guidelines for Clostridium dif-
Health Division; Revised 2015. ficile infection in adults: 2010 update by the Society for
Healthcare Epidemiology of America (SHEA) and the In-
13. Sirinavin S, Garner P. Antibiotics for treating salmonella gut
fectious Diseases Society of America (IDSA). Infect Control
infections. Cochrane Database Syst Rev. 2000;CD001167.
Hosp Epidemiol. 2010;31:431-455.
14. DuPont HL. Bismuth subsalicylate in the treatment and
37. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for
prevention of diarrheal disease. Drug Intell Clin Pharm.
diagnosis, treatment, and prevention of Clostridium difficile
1987;21:687-693.
infections. Am J Gastroenterol. 2013;108:478-498.
15. Pepto-Bismol (bismuth subsalicylate) package insert.
38. Metronidazole. Lexi-Drugs. Lexicomp Online. Wolters Kluwer
Cincinnati, OH: Procter & Gamble; 2014.
Health, Inc. http://online.lexi.com. Accessed April 12, 2016.
16. Schiller LR. Diarrhea and malabsorption in the elderly.
39. Vancocin (vancomycin) prescribing information. Exton, PA:
Gastroenterol Clin N Am. 2009;38:481-502.
ViroPharma Incorporated; 2005.
17. Pray WS. Nonprescription Product Therapeutics. 2nd ed.
40. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A compari-
Baltimore, MD: Lippincott Williams & Wilkins; 2005.
son of vancomycin and metronidazole for the treatment of
18. Fernandez-Banares F, Esteve M, Viver JM. Fructose-sorbitol Clostridium difficile-associated diarrhea, stratified by dis-
malabsorption. Curr Gastroenterol Rep. 2009;11:368-374. ease severity. Clin Infect Dis. 2007;45:302-307.
19. Longstreth GF, Thompson WG, Chey WD, Houghton LA, 41. Dificid (fidaxomicin) prescribing information. Whitehouse
Mearin F, Spiller RC. Functional bowel disorders [erratum Station, NJ: Merck & Co; 2015.
in Gastroenterology. 2006;131:688]. Gastroenterology.
42. Louie TJ, Miller MA, Mullane KM, et al; OPT-80-003 Clinical
2006;130:1480-1491.
Study Group. Fidaxomicin versus vancomycin for Clostridium
20. Lovell RM, Ford AC. Global prevalence of and risk factors difficile infection. N Engl J Med. 2011;364:422-431.
for irritable bowel syndrome: a meta-analysis. Clin Gastro-
43. Diemert DJ. Prevention and self-treatment of traveler’s diar-
enterol Hepatol. 2012;10:712-721.
rhea. Clin Microbiol Rev. 2006;19:583-594.
21. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome:
44. Connor BA. Travelers’ diarrhea. Centers for Disease Control
a clinical review. JAMA. 2015;313:949-958.
and Prevention Health Information for International Travel
22. Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Man- 2016. Updated July 10, 2015. wwwnc.cdc.gov/travel/
agement of Functional Bowel Disorders. American College yellowbook/2016/the-pre-travel-consultation/travelers-
of Gastroenterology monograph on the management of ir- diarrhea. Accessed April 21, 2016.
ritable bowel syndrome and chronic idiopathic constipation.
45. Ross AG, Olds GR, Cripps AW, Farrar JJ, McManus DP.
Am J Gastroenterol. 2014;109:S2-S26.
Enteropathogens and chronic illness in returning travelers