Bacterial Infections

The bacterial species most commonly associated with gastrointestinal infection and infectious diarrhea in the United States are Shigella spp., Salmonella spp., Campylobacter spp., Yersinia spp., Escherichia spp., Clostridium spp., and Staphylococcus spp.
Antibiotics are not essential in the treatment of most mild diarrheas, and empirical therapy for acute gastrointestinal infections may result in unnecessary antibiotic courses.

Enterotoxigenic (cholera-like) Diarrhea

Cholera (Vibrio cholerae)

Vibrio cholerae is the organisms that most often causes human epidemics and pandemics. Four mechanisms for transmission have been proposed: animal reservoirs, chronic carriers, asymptomatic or mild disease victims, or water reservoirs.

TABLE. Clinical Assessment of Degree of Dehydration in Children Based on Percentage of Body Weight Loss^a

Variable	Mild, 3%-5%	Moderate, 6%-9%	Severe, в‰Ґ10%
Blood pressure	Normal	Normal	Normal to reduced
Quality of pulses	Normal	Normal or slightly decreased	Moderately decreased
Heart rate	Normal	Increased	Increased (bradycardia in severe cases)
Skin turgor	Normal	Decreased	Decreased
Fontanelle	Normal	Sunken	Sunken
Mucous membranes	Slightly dry	Dry	Dry
Eyes	Normal	Sunken orbits/decreased tears	Deeply sunken orbits/decreased tears
Extremities	Warm, normal capillary refill	Delayed capillary refill	Cool, mottled
Mental status	Normal	Normal to listless	Normal to lethargic or comatose
Urine output	Slightly decreased	<1 mL/kg/h	<1 mL/kg/h
Thirst	Slightly increased	Moderately increased	Very thirsty or too lethargic to indicate
Fluid replacement	oral rehydration therapy 50 mL/kg over 2-4 h	oral rehydration therapy 100 mL/kg over 2-4 h	Ringer lactate 40 mL/kg in 15-30 min, then 20-40 mL/kg if skin turgor, alertness, and pulse have not returned to normal or
Fluid replacement	Replace ongoing losses with low-sodium oral rehydration therapy (40-60 mEg/L Na⁺) at 10 mL/kg per stool or emesis	Replace ongoing losses with low-sodium oral rehydration therapy (40-60 mEq/L Na⁺) at 10 mL/kg per stool or emesis	Ringer lactate or NS 20 mL/kg, repeat if necessary, and then replace water and electrolyte deficits over 1-2 days Followed by oral rehydration therapy 100 mL/kg over 4 hours. Replace ongoing losses with low-sodium oral rehydration therapy (40-60 mEq/L Na⁺) at 10 mL/kg per stool or emesis
^aPercentages vary among authors for each dehydration category; hemodynamic and perfusion status is most important; when unsure of category, therapy for more severe category is recommended. oral rehydration therapy, oval rehydration therapy.

TABLE. Comparison of Common Solutions Used in Oral Rehydration and Maintenance

Product	Na (mEq/L)	K (mEq/L)	Base(mEq/L)	Carbohydrate (mmol/L)	Osmolality (mOsm/L)
Naturalyte (unlimited beverage)	45	20	48	140	265
Pediatric electrolyte (NutraMax)	45	20	30	140	250
Pedialyte (Ross)	45	20	30	140	250
Infalyte (formerly Ricelyte; Mead Johnson)	50	25	30	70	200
Rehydralyte (Ross)	75	20	30	140	310
WHO/UNICEF oral rehydration salts	90	20	30	111	310
Cola	2	0	13	700	750
Apple juice	5	32	0	690	730
Chicken broth	250	8	0	0	500
Sports beverage	20	3	3	255	330

Most pathology of cholera is thought to result from an enterotoxin that increases cyclic AMP-mediated secretion of chloride ion into the intestinal lumen, which results in isotonic secretion (primarily in the small intestine) exceeding the absorptive capacity of the intestinal tract (primarily the colon).
The incubation period of V. cholerae is 1 to 3 days.
Cholera is characterized by a spectrum from the asymptomatic state to the most severe typical cholera syndrome. In the most severe state, this disease can progress to death in a matter of 2 to 4 hours if not treated.

Treatment

The mainstay of treatment for cholera consists of fluid and electrolyte replacement with oral rehydration therapy. Rice-based rehydration formulations are the preferred oral rehydration therapy for cholera patients. In patients who cannot tolerate oral rehydration therapy intravenous therapy with Ringer’s lactate can be used.
Antibiotics shorten the duration of diarrhea, decrease the volume of fluid lost, and shorten the duration of the carrier state (see Table Comparison of Common Solutions Used in Oral Rehydration and Maintenance). A single dose of oral doxycycline is the preferred agent. In children younger than 7 years of age, trimethoprim-sulfamethoxazole, erythromycin, and furazolidone are preferred.

Escherichia coli

Escherichia coli gastrointestinal disease may be caused by enterotoxigenic E. coli, enteroinvasive E. coli, enteropathogenic E. coli, entero- adhesive E. coli, and enterohemorrhagic E. coli. Enterotoxigenic E. coli is now incriminated as being the most common cause of traveler’s diarrhea.
Enterotoxigenic E. coli is capable of producing two plasmid-mediated enterotoxins: heat-labile toxin and heat-stable toxin. The net effect of either toxin on the mucosa is production of a cholera-like secretory diarrhea.
Nausea and watery stools, with or without abdominal cramping, are characteristic of the disease caused by enterotoxigenic E. coli. Most enterotoxigenic E. coli diarrhea resolves within 24 to 48 hours without complication.
Most cases respond readily to oral rehydration therapy, and although antibiotic therapy is seldom necessary, prophylaxis has been shown to effectively prevent the development of enterotoxigenic E. coli diarrhea.
Fluid and electrolyte replacement should be initiated at the onset of diarrhea.
Antibiotics used for treatment are found in Table Recommendations for Antibiotic Therapy.

TABLE. Recommendations for Antibiotic Therapy

Pathogen	First-Line Agents	Alternative Agents
Enterotoxigenic (Cholera-Like) Diarrhea
Vibrio cholerae O1 or O139	Doxycline 300 mg oral single dose; tetracycline 500 mg orally 4 times daily x 3 days; or trimethoprim-sulfamethoxazole DS tablet twice daily x 3 days; norfloxacin 400 mg orally twice daily x 3 days; or ciprofloxacin 500 mg orally twice daily x 3 days or 1 g orally single dose	Chloramphenicol 50 mg/kg intravenous every 6 h, erythromycin 250-500 mg PO every 6-8 h, and furazolidone
Enterotoxigenic E. coli	Norfloxacin 400 mg or ciprofloxacin 500 mg orally twice daily x 3 days	Trimethoprim-sulfamethoxazole DS tablet every 12 h
C. difficile	Metronidazole 250 mg 4 times daily to 500 mg 3 times daily x 10 days	Vancomycin 125 mg orally four times daily x 10 days; bacitracin 20,000-25,000 units 4 times daily x 7-10 days
Invasive (Dysentery-Like) Diarrhea
Shigella species^a	Trimethoprim-sulfamethoxazole DS twice daily x 3-5 days	Ofloxacin 300 mg, norfloxacin 400 mg, or ciprofloxacin 500 mg twice daily x 3 days, or nalidixic acid 1 g/day x 5 days; azithromycin 500 mg orally x 1, then 250 mg orally daily x 4 days.
Salmonella
Nontyphoidal^a	Trimethoprim-sulfamethoxazole DS twice daily; ofloxacin 300 mg, norfloxacin 400 mg, or ciprofloxacin 500 mg twice daily x 5 days; or ceftriaxone 2 g intravenous daily or cefotaxime 2 g intravenous 3 times daily x 5 days	Azithromycin 1000 mg orally x 1 day, followed by 500 mg orally once daily x 6 days
Enteric fever	Ciprofloxacin 500 mg orally twice daily x 3-14 days (ofloxacin and perfloxacin equally efficacious)	Azithromycin 1000 mg orally x 1 day, followed by 500 mg daily x 5 days; or cefixime, cefotaxime, and cefuroxime; or chloramphenicol 500 mg 4 times daily orally or intravenous x 14 days
Campylobacter^a	Erythromycin 500 mg orally twice daily x 5 days; azithromycin 1000 mg orally x 1 day, followed by 500 mg daily or clarithromycin 500 mg orally twice daily	Ciprofloxacin 500 mg or norfloxacin 400 mg orally twice daily x 5 days
Yersinia species^a	A combination therapy with doxycycline, aminoglycosides, trimethoprim-sulfamethoxazole, or fluoroquinolones
Traveler’s Diarrhea
Prophylaxis^a	Norfloxacin 400 mg or ciprofloxacin 500 mg orally daily (in Asia, Africa, and South America); trimethoprim-sulfamethoxaxole DS tablet orally daily (in Mexico)
Treatment	Norfloxacin 400 mg or ciprofloxacin 500 mg orally twice daily x 3 days, or trimethoprim-sulfamethoxazole DS tablet orally twice daily x 3 days (in Mexico), or azithromycin 500 mg orally once daily x 3 days (only in areas of high prevalence of quiniolone-resistant Campylobacter species, such as Thailand)
^aFor high-risk patients only.

Effective prophylactic agents include doxycycline, trimethoprim/ sulfamethoxazole, or a fluoroquinolone.

Pseudomembranous Colitis (Clostridium difficile)

Pseudomembranous colitis results from toxins produced by C. difficile. It occurs most often in epidemic fashion and affects high-risk groups such as the elderly, debilitated patients, cancer patients, surgical patients, any patient receiving antibiotics, patients with nasogastric tubes, or those who frequently use laxatives.
Pseudomembranous colitis has been associated most often with broad-spectrum antimicrobials, including clindamycin, ampicillin, or third-generation cephalosporins.
Pseudomembranous colitis may result in a spectrum of disease from mild diarrhea to enterocolitis. In colitis without pseudomembranes, patients present with malaise, abdominal pain, nausea, anorexia, watery diarrhea, low-grade fever, and leukocytosis. With pseudomembranes, there is more severe illness with severe abdominal pain, perfuse diarrhea, high fever, and marked leukocytosis. Symptoms can start a few days after the start of antibiotic therapy to several weeks after antibiotics have been stopped.
Diagnosis is made by colonoscopic visualization of pseudomembranes, finding cytotoxins A or B in stools, or stool culture for C. difficile.
Initial therapy of Pseudomembranous colitis should include discontinuation of the offending agent. The patient should be supported with fluid and electrolyte replacement.
Both vancomycin and metronidazole are effective, but metronidazole 250 mg orally 4 times daily is the drug of choice. Oral vancomycin, 125 mg orally 4 times daily, is second-line therapy. It should be reserved for patients not responding to metronidazole, organisms resistant to metronidazole, patients allergic or intolerant to metronidazole, other treatments that include alcohol-containing solutions, patients who are pregnant or younger than 10 years, critically ill patients, or those with diarrhea that is caused by Staphylococcus aureus.
Drugs that inhibit peristalsis, such as diphenoxylate, are contraindicated.
Relapse can occur in 20% to 25% of patients and may be treated with metronidazole or vancomycin for 10 to 14 days.