Bacterial Diarrhea

Etiology

Diarrhea can be acute or chronic: acute is defined as lasting less than two weeks, chronic lasts more than a month, between 2 to 4 weeks is dubbed persistent. 

Chronic diarrhea may reflect a functional issue as in cases of irritable bowel syndrome. Still, chronic diseases, including inflammatory bowel disease (IBD), malabsorption, and medication side effects, can be other etiologies. Chronic diarrhea is more often non-infectious, although chronic infections produce it as well. Bacterial infection with Clostridiodes difficile can result in chronic diarrhea, as can protozoa such as Giardia, Entamoeba, Cryptosporidium, or Isospora. Patients at increased risk of chronic diarrhea from these organisms include young children, the elderly, immune-compromised, or international travelers.

Acute diarrhea usually has an infectious etiology. Most of the episodes of acute diarrhea are viral, with common pathogens including norovirus, rotavirus, or adenovirus. Rehydration is the mainstay of treatment, especially in children who have increased morbidity and mortality. In developing countries, diarrhea is a major cause of mortality in young children, and prompt treatment with oral rehydration solutions (ORS) replaces water and electrolytes lost during diarrheal episodes, significantly reducing morbidity and mortality.[5]

Bacterial diarrhea can produce more severe forms of acute diarrhea. Dysentery is diarrhea associated with blood (plus or minus mucus) and represents more invasive infection. The most frequently identified organisms causing bacterial diarrhea are Escherichia coli (most common worldwide), Shigella, Salmonella, Campylobacter (most common in children), Yersinia, and Clostridium spp.

Traveler's diarrhea can be most commonly the result of Shiga-toxin producing E. coli (STEC), as well as Shigella, Salmonella, Entamoeba histolytic, Giardia, Cryptosporidium, Cyclospora, and enteric viruses.

Epidemiology

There are 1.7 billion cases of childhood diarrhea every year, and diarrhea is the second leading cause of mortality in children under five years old, with about 525,000 childhood deaths annually. Most of this mortality is preventable through access to care and rehydration therapy. Complications such as ensuing malabsorption can be seen that impact child growth after recovery from the immediate illness. There are an estimated 5.2 million cases of bacterial diarrhea in the U.S. annually, with 80% of infections resulting from foodborne contamination.[6]

Global estimates for the prevalence of specific types of bacterial diarrhea among all diarrheal causes include E.coli 10% to 25%, Shigella 10%, Salmonella 3%, Campylobacter 3 to 6%.[7][8] and bacterial diarrhea in the U.S. was estimated to be approximately 31% of all diarrheas.[9] The proportion of bacterial pathogens resulting in foodborne diarrheal illness in the U.S. is estimated to be: Salmonella 15.4%, Campylobacter 11.8%, Shigella 4.6 %, Shiga-toxin producing E. coli (STEC) around 3%.[10]

Pathophysiology

In bacterial diarrhea, the pathogen attaches to the epithelium and produce toxins that increase the intracellular cyclic-AMP (adenosine monophosphate), a secondary messenger. This ultimately revs up the secretory process in the enterocytes. The toxins may also provoke the release of cytokines responsible for chemotaxis and production of eicosanoids (prostaglandins), worsening the intra-luminal unbalance of water. This excess of water and electrolytes in the intestinal lumen draws more fluid into the lumen, further worsening diarrhea with this osmotic effect.[11]

History and Physical

A history of food intake can help with the diagnosis of foodborne illness, and timing of illness onset after food intake may aid in determining food sources of greatest concern for contamination. Travel history can impact the consideration of additional pathogens and potentially broaden the differential diagnostic considerations.[12] Questions about the job, hobbies, pets, and residential status are all important. Medication use should be documented and carefully reviewed. Almost all medications can have a side effect of diarrhea, and it can be of concern, especially during the initial phases of using new medicine. Some that are more likely to cause diarrhea are antacids, magnesium, laxatives, nonsteroidal inflammatory drugs (NSAIDs), antibiotics, chemotherapy agents, and metformin. The use of antibiotics predisposes to Clostridiodes difficile associated diarrhea. 

The number, consistency, volume, and other characteristics of the stool should be determined. The diagnostician should seek associated symptoms. Small intestinal diarrhea is usually voluminous, watery, and comes with abdominal discomfort, bloating, and pain. Large intestinal diarrhea is less voluminous and comes with painful bowel movements and minimal abdominal discomfort. E.coli (toxicogenic - STEC), Salmonella spp., Vibrio cholerae, Clostridium perfringens affect the small bowel, whereas Campylobacter, Shigella, Yersinia, E. coli (enteroinvasive) primarily involve the colon.[13][14][3]

Fever, blood, and mucus in the stool are usually concerning symptoms and are a sign of enteroinvasive disease in the colon. When there is clear red blood in the stool, chances of presence of STEC will increase. STEC starts with watery diarrhea that will turn bloody in 1 to 5 days. Severe cramping is usually present, and diarrhea is more than five times a day. STEC is the most common reason for renal failure and hemolytic uremic syndrome in children. 

General medical history is essential. Underlying immunosuppressed or compromised states (cancer, transplant, HIV,etc.) can increase the risk of specific pathogens or increase the severity of illness. Certain medical conditions are associated with certain organisms (i.e., cirrhosis with Vibrio, hemochromatosis with Yersinia, pregnancy with Listeria).

Reheated fried rice is associated with Bacillus cereus infection, raw beef like a hamburger is associated with STEC, raw milk can harbor Salmonella, and Campylobacter, seafood such as shellfish can have contamination with Vibrio cholerae or V. parahemolyticus, undercooked pork is associated with diarrhea from Yersinia spp.

Persons with human immunodeficiency virus (HIV) have an increased risk of diarrhea caused by Cryptosporidium, Microspora, Isospora, or Cytomegalovirus. Listeriosis is associated with immune suppression as well as with pregnancy. 

Certain medications can cause diarrhea: antibiotics, laxatives, antiacids, colchicine, and chemotherapy regimen have all been implicated. Microscopic colitis or radiation colitis can also be a problem. 

General physical examination with a focus on vital signs and signs of hypovolemia is of importance. The abdominal exam should evaluate for distension, tenderness, presence of normal bowel sounds or ileus, and clinical evidence of peritonitis.

Clostridiodes difficile infection usually presents with watery diarrhea, nausea, fever, anorexia in the setting of recent antibiotic use. Antibiotic use can be up to 10 weeks before the symptom onset. Although any antibiotic can cause this, the most frequently associated are fluoroquinolones, penicillins, and clindamycin. Very low potassium levels can also present in this entity. 

Salmonella infection is usually associated with poultry, eggs, and milk. The enteric fever version results from S. typhi and S. paratyphi. It presents as a febrile illness with abdominal pain, fever, bradycardia, pulse-temperature disassociation, rose spots, hepatosplenomegaly, anemia, and leukopenia. Diarrheal illness is usually from non-typhoidal types, which are commonly isolated from the diarrheal stool. They are typically self-limited courses of diarrhea, fever, cramps, and nausea. No antibiotics are recommended ordinarily for non-typhoidal unless the host is immunocompromised. 

Shigellosis presents with abdominal cramps, high fever, bloody mucosal diarrhea, tenesmus, leukemoid reaction, and lasts for up to seven days. It is usually self-limited, but complications can be reactive arthritis, seizure, hemolytic-uremic syndrome, rectal prolapse, toxic megacolon, obstruction, and perforation.

Yersiniosis presents with abdominal pain in the right lower quadrant, fever, vomiting, diarrhea, leukocytosis, and can be easily mistaken for appendicitis. "Epidemic appendicitis" describes the sudden appearance of many cases of appendicitis-like patients that is secondary to a yersinia epidemic.

Evaluation

Although most patients with diarrhea will not require any laboratory evaluations, tests are a recommended step after several days have passed with no resolution of symptoms or if the initial treatments were unsuccessful. If the disease is severe, refractory, or affecting high-risk patients, testing may merit more urgent consideration.

Stool studies should preferably take place using a fresh diarrheal stool. The presence of white blood cells (fecal leukocytes) might be a sign of inflammation, although the sensitivity is 70 percent and specificity only 50 percent.[15] Fecal calprotectin is a potential marker of neutrophil activity and can differentiate inflammatory from non-inflammatory diarrhea. Sensitivity and specificity in the 90% range have been proposed for this test.[16] Fecal lactoferrin is another potential marker of neutrophils and might be of help in differentiating infectious diarrhea from inflammatory bowel disease (IBD).[17] Red blood cells will indicate enteroinvasive disease that is causing bleeding. Ova and parasite recognition will confirm these sources of infection. Quantitative stool fat shows an abnormal gastrointestinal mucosa and can help differentiate malabsorption syndromes.[18]

Multi-pathogen molecular panels that identify the genetic material of the organisms can be helpful and may identify the source of infection within hours rather than days for standard culture techniques.[19] Bacterial stool cultures may be indicated to confirm specific bacterial pathogens or to aid in determining antimicrobial susceptibility patterns to guide treatment.

For C. difficile diagnosis, nucleic acid amplification is a process for diagnosis confirmation. Initial screening usually involves stool tests for C. difficile toxin and glutamate dehydrogenase (GDH) antigen. The presence of pseudomembranous colitis either in imaging or endoscopy is also beneficial.

Treatment / Management

Rehydration is the mainstay of treatment of bacterial diarrhea. This strategy is possible through the administration of oral or intravenous fluids. The use of ORS containing sodium, potassium, and glucose delivered in small, frequent volumes is the recommendation in patients who can tolerate this intake, and intravenous (IV) rehydration reserved for those that fail oral rehydration.

All patients should be encouraged to eat nutrient-rich foods to counter diarrhea as soon as dehydration is adequately managed; rather than restrict dietary intake. Breast-fed infants should continue their usual feedings if possible. Zinc supplementation is reported to reduce both the stool volume and stool frequency by 30 percent and is a consideration in severe cases.[20] Although diets such as BRAT (banana, rice, apple, and toast) or bland diet have been proposed to improve the condition and are somewhat better tolerated; no reliable data or prospective studies are available to confirm this, and the assumptions are mostly based on limited studies or personal experiences. Similarly, the exclusion of certain foods, such as dairy products, is not evidence-based. A systematic review suggested that there is little evidence for or against dietary restrictions in diarrhea, and a typical diet can be resumed as tolerated.[21](A1)

Avoid symptomatic treatment with antimotility agents, as their use decreases peristalsis and prolongs the presence of bacteria and toxins in the gut, therefore potentially worsening the disease. Treatment with antimotility agents and reduction of stool volume does not alleviate the need for supportive rehydration.[22](A1)

Some patients with bacterial diarrhea will need antibiotic therapy.[23] When bacterial diarrhea is suspected, the patient is toxic appearing, dysentery is present, or the patient is immunocompromised; empiric antibiotic treatment may be indicated.[2] Whenever local antimicrobial susceptibility data are available, they should guide empiric treatment, and patient stool pathogen results should be used to guide definitive therapy. (A1)

Lactobacillus GG and Saccharomyces boulardii and other probiotics might be used in infectious diarrhea and traveler's diarrhea, although the effects are modest at best.[24] The exact type, dosage, and duration of treatment are also not known. (A1)

Admission is necessary in dehydration, shock, severe nausea and vomiting, the need for intravenous antibiotics, the possibility of complications, and on a case by case basis. Scoring systems have been proposed to facilitate recognizing those with severe diarrhea based on temperature, arterial pressure, white blood cell count, and stool white cells.[25] (B2)

Vaccination for specific travelers against cholera and typhoid may be recommended, based upon the travel destination and country of origin. Vaccination is also available against rotavirus in infants.

Differential Diagnosis

Bacterial diarrhea is part of the differential diagnosis for systemic illness with acute onset of diarrhea, including the following:

• Viral systemic diseases including viral gastroenteritis, or multi-system viral infections including adenovirus, and influenza merit consideration.
• Protozoal diarrhea, such as Giardia or Cryptosporidium, can also present similarly. In endemic areas, consideration of arboviral syndromes or malaria may also be necessary.[26]

Non-infectious causes should also be excluded, such as

• inflammatory bowel disease (IBD)[27],
• irritable bowel syndrome (IBS)[28],
• malabsorption syndromes (celiac disease, Whipple's disease),
• cystic fibrosis,
• carcinoid tumor,
• lactose intolerance,
• hyperthyroidism, and
• antibiotic-induced diarrhea[29]

Prognosis

Prognosis is usually excellent in developed countries with appropriate support, hydration, and antibiotics. In developing areas where access to care may limit opportunities for rehydration, morbidity, and mortality are increased, particularly for vulnerable populations.

Complications

Toxic megacolon, gastrointestinal perforation, reactive arthritis, persistent diarrhea, bacteremia and sepsis, hemolytic-uremic syndrome, Guillain-Barre syndrome are all possible complications of this disease, based upon the causative bacterial pathogen.