1. 
   

   What questions in the diarrhea history will guide the need for diagnostic testing?

   
   
2. 
   

   What is the yield of commonly ordered diagnostic stool tests?

   
   
3. 
   

   What is a practical algorithm to guide rational diagnostic stool testing?

   
   
4. 
   

   What are practical supportive therapies for hospitalized patients with diarrhea?

   
   
5. 
   

   What are the key preventative measures for preventing the spread of infectious diarrhea?

Definition

The typical adult eating a western diet excretes 100–200 grams of fecal matter a day, which consists of water, electrolytes, indigestible matter, unabsorbed food, intestinal secretions, epithelial cells, and enteric bacteria. Diarrhea is defined as an abnormal increase in excretion of fecal matter to >200 grams a day. Although no official definition for nosocomial diarrhea exists, if surmised from the definition of acute diarrhea, it is diarrhea of <2 weeks duration that first presents during an inpatient stay.

The epidemiology of acute nosocomial and acute community-acquired diarrhea are quite disparate, and this chapter will focus on the former. The usual bacterial, viral, and protozoal suspects in community-acquired diarrhea are rare culprits in nosocomial diarrhea. They will be mentioned in this chapter, to sufficiently discuss the differential diagnosis of acute diarrhea, but will be appropriately deemphasized as likely causes of diarrhea in hospitalized patients.

Incidence

Diarrhea is 1 of the most common afflictions in hospitalized patients, occurring in 33%-50% of inpatients. Patients who acquire diarrhea while in the hospital have longer lengths of stay and higher mortality than those who do not. Diarrhea also is associated with more diagnostic testing (stool studies, imaging exams, electrolyte monitoring), and interventions (intravenous fluids, electrolyte supplementation, and medication adjustments). It also creates issues for sanitation and quality of life, especially in patients that are not independent in mobility and self-care.

The differential diagnosis for diarrhea in hospitalized patients is extensive, but is most conveniently dichotomized into infectious and noninfectious etiologies.

There are more than 200 million cases of infectious diarrhea in the U.S. each year, resulting in 1.8 million hospitalizations. Most infectious diarrheas are acquired by fecal-oral transmission, by person-to-person contact, or by food/liquids (although the latter is highly unusual in the hospital setting). Contagious spread by person-to-person contact also includes transmission through fomites, such as stethoscopes, bedside commodes, or other medical equipment. The vast majority of infectious diarrhea in inpatients is caused by Clostridium difficile. A full discussion of Clostridium difficile-associated diarrhea (CDAD) diagnosis, management, and prevention can be found in Chapter 188 C difficile colitis. However, a few other bacterial, viral, and protozoal agents can be acquired in the hospital setting, and these are discussed below.

Bacterial Pathogens

The bacterial pathogens that commonly cause community-acquired diarrhea are rarely a cause of diarrhea in the hospitalized patient. However, cases do arise. In the U.S., there are 5.2 million cases of bacterial diarrhea, 46,000 hospitalizations, and 1500 deaths annually. The majority of these occur in outpatients as a result of food-borne transmission. Person to person transmission is less common, and usually occurs with pathogens that only require a small inoculum to cause disease (Table 80-1). The usual bacterial suspects include Salmonella spp, Shigella spp, Campylobacter spp, and Escherichia coli 0157:H7.

Salmonella typhi is almost always acquired by person to person transmission, from an acutely infected or chronic carrier, but rarely can be transmitted through food or water. Such was the case of Mary Mallon “Typhoid Mary,” a healthy Irish immigrant cook who, as an asymptomatic carrier, transmitted the infection to at least 22 people over 7 years before being identified as the source of the outbreaks. The rarity of Salmonella typhi outbreaks in the U.S. is a reflection of exemplary hygiene and sewage standards. Transmissibility of the organism depends on the density of the organism in the infected person, and the infectivity of the strain. Generally a high density of inoculum is required to result in clinical symptoms, based on voluntary experimental ingestions. Nontyphoidal Salmonella spp, on the other hand, are rarely transmitted person to person, usually derive from an environmental animal reservoir (farm animals), and require a much lower density of inoculum to cause clinical infection.

Campylobacter spp, similar to nontyphoidal Salmonella spp, is rarely transmitted person to person, and is usually linked to contaminated food sources (meat, dairy, or water). Although a small inoculum is required for infection, widespread outbreaks rarely occur, because most patients remain asymptomatic.

Escherichia coli 0157:H7 transmission also usually occurs through contaminated food (meats or fertilized fruits/vegetables), although secondary person-to-person transmission can subsequently occur. The infamous large outbreak in the early 1990s was linked to contaminated hamburger, and secondary infection was rampant, occurring in up to 20% of close contacts.

Shigella spp spreads from person to person or through contaminated food, but has no environmental reservoir (similar to salmonella typhi). It is highly contagious, with a low density of inoculum required to result in clinical infection. It therefore commonly causes outbreaks, usually within households and day care centers.

Other causes of bacterial diarrhea in hospitalized patients include Klebsiella oxytoca, Klebsiella pneumonia, Staphylococcus aureus, and Clostridium perfringens, all of which have been implicated in causing a toxin-associated diarrheal illness that can be clinically indistinguishable from CDAD. A small case series of patients with (non-Clostridium difficile) antibiotic-associated hemorrhagic colitis found that a majority of cases were caused by Klebsiella oxytoca, which produces a cytotoxin that causes epithelial cell death. Similarly there are strains of Klebsiella pneumonia that produce an enteropathogenic toxin that causes hemorrhagic diarrhea. There are also some strains of Staphylococcus areus that produce an enteropathogenic toxin, and may be the etiologic agent in patients with (non-Clostridium difficile) antibiotic-associated diarrhea. Enterotoxin producing Clostridium perfringens has also been suspected to be a causal agent in nosocomial diarrheas. Although there is still some disagreement about the role that these organisms play in non-C difficile toxigenic diarrheal syndromes, there does appear to be evidence of their existence.

Candida spp have also been implicated in nosocomial diarrhea. It is thought to cause a secretory diarrhea (without evidence of colitis) in critically ill or debilitated patients, but it is unclear how to treat or manage these patients.

Viruses/Protozoa

Viral outbreaks of diarrhea occur more commonly than bacterial outbreaks, both in the community and hospital setting. The most common viral causes of acute infectious diarrhea include the caliciviruses (Norwalk and Sapporo viruses), rotavirus (primarily in children), adenovirus, and astrovirus.

By far the most common are the caliciviruses, estimated to account for more than 90% of acute gastrointestinal outbreaks in the U.S. They are associated with a high infectivity rate (with attack rates reported to be as high as 50% in close contacts) and a low density of required inoculum. Cruise ships notoriously are headlined with these outbreaks, but they can (and have) occurred in medical environments, including nursing homes and hospitals. These viruses are transmitted both by infected food and water, and by secondary person-to-person spread. The viral particles are present in both the vomitus and the feces (as opposed to bacterial enteritis, in which the bacteria are present only in stool), increasing the likelihood of person-to-person transmission. Unfortunately, these viruses also persist on environmental surfaces and are resistant to ordinary cleaning agents (although are inactivated by household bleach).

Rotavirus infections tend to cause symptomatic disease only in children. Similar to the caliciviruses, the organism can remain in the environment for prolonged periods of time and are difficult to eradicate with routine cleaning agents. Enteric adenoviral strains also rarely produce symptomatic diarrheal disease in adults. Astroviral outbreaks spread from person to person and have occurred in the hospital setting. Although they much more commonly occur in pediatric populations, they also afflict the elderly, immunocompromised, and institutionalized.

Protozoal causes of acute diarrhea are most commonly caused by Giardia lamblia, cryptosporidium, and Entamoeba histolytica. These are usually connected with contaminated water sources, with secondary person-to-person transmission occurring via the fecal-oral route. They are transmitted via a very small inoculum and are therefore highly transmissible. These protozoa usually cause outbreaks in schools and daycare settings, and medical setting outbreaks are highly unusual.

Immunocompromised patients (especially HIV with CD4 < 50) clearly have a more extensive infectious differential diagnosis for nosocomial diarrhea. The additional organisms that should be considered include cryptosporidia, microsporidia, cyclospora, isospora, mycobacterium avium complex (MAC), and cytomegalovirus (CMV).

Noninfectious nosocomial diarrhea can be due to a host of insults, including the introduction of new agents or therapies (medications, foods, additives, enteral feedings, contrast agents, radiation therapy), and new diagnoses (fecal impaction, inflammatory bowel disease, opiate withdrawal, transplant rejection, GI bleeding, fat malabsorption, and biliary obstruction).

New Agents or Therapies

Medications are a common offender for noscomial diarrhea, and a careful review of medications is warranted (Table 80-2). Antibiotic-associated diarrhea is a common occurrence, the frequency of which depends on the antimicrobial agent, ranging from 2–25% (with no significant difference between intravenous and oral antibiotics). The spectrum of disease caused by antibiotic-associated diarrhea can range from uncomplicated loose stools to frank colitis. Antibiotics can result in diarrhea by two primary mechanisms. Erythromycin, which is a motilin receptor agonist, directly stimulates gut motility; clavulanate also can activate gut motility, albeit less dramatically. Virtually all antibiotics can indirectly impact gut motility by killing some of the fecal flora; this can reduce the metabolism of carbohydrates, resulting in an osmotic diarrhea.