GI Infections: GI Infections: Bacteria and Toxins

0:00Welcome to Board Pearls. This is episode three of five of the GI Infections chapter, in the Special Populations and Acute or Supportive Care module. This episode is the bacteria and toxins behind acute diarrhea. The first patient is a woman back from Thailand with bloody diarrhea. Her case shows when travelers' diarrhea needs an antibiotic, which antibiotic fits the region, why rifaximin can't treat invasive disease, and when loperamide is safe. Her culture then leads through the four organisms behind most bloody diarrhea, Campylobacter, nontyphoidal Salmonella, Shigella, and Shiga toxin-producing E. coli, and why Salmonella usually gets no antibiotic while Shigella usually does. A man who ate an undercooked hamburger shows why one of them must get neither antibiotics nor loperamide. A man with iron overload and a pregnant woman show the bacteria that target particular hosts, Vibrio, Yersinia, and Listeria. The episode ends with the toxins that act within hours and the problems that linger after infection clears.

1:04Here's the first patient. A twenty-nine-year-old woman returned four days ago from two weeks in Thailand. She's had three days of cramping and diarrhea that began watery and turned bloody, a temperature of thirty-nine point two, and two missed workdays. She took loperamide from her travel kit yesterday.

1:20She has travelers' diarrhea that has become dysentery, bloody diarrhea with fever, and that points to an invasive bacterium. Travelers' diarrhea affects thirty to fifty percent of people traveling from high-income to low- and middle-income regions, and bacteria cause about eighty percent. Enterotoxigenic and enteroaggregative E. coli account for half to three-quarters of cases worldwide, while the invasive species vary by region: Campylobacter dominates in Southeast Asia, Shigella in South Asia and Africa, and nontyphoidal Salmonella everywhere. Most cases resolve with hydration and selective use of antimotility drugs in three to five days, so the decisions are when an antibiotic helps, which antibiotic fits the region, and when antibiotics or antimotility drugs are dangerous.

2:08Her fever and blood mean she needs an antibiotic. The indications are moderate-to-severe disease, fever, dysentery, meaning blood or mucus in the stool, or illness severe enough to stop travel or work. She has fever, blood, and missed work.

2:24Her destination decides which antibiotic. Azithromycin, one gram once or five hundred milligrams daily for three days, is the preferred empiric drug for travel to Southeast Asia, where Campylobacter is widely resistant to fluoroquinolones, and it's increasingly preferred elsewhere for the same reason. Ciprofloxacin, five hundred milligrams twice daily for one to three days, remains an option where resistance isn't high. Coming from Thailand, she gets azithromycin, because ciprofloxacin would target an organism likely resistant to it.

2:55Rifaximin is the wrong drug for her. Rifaximin, two hundred milligrams three times daily for three days, is approved by the Food and Drug Administration for noninvasive E. coli travelers' diarrhea in adults, but it doesn't cover invasive Salmonella, Shigella, or Campylobacter. It's essentially unabsorbed and acts only in the gut lumen, while invasive organisms reach the lamina propria, where a systemically absorbed drug is needed. So it's unsuitable for febrile or bloody illness like hers.

3:24Her loperamide should stop. Added to an antibiotic, loperamide shortens illness by one to two days, but only in diarrhea without fever or blood. It's contraindicated when Shiga toxin-producing E. coli is suspected, because slowing transit prolongs exposure to the toxin and raises the risk of hemolytic uremic syndrome. With fever and blood, she stops it. Travelers can be told that loperamide is for watery diarrhea without fever, not for fever or blood.

3:53Her stool culture grows Campylobacter. It's the leading cause of acute bacterial diarrhea in the United States, acquired mainly from poultry and from animal contact, often a new puppy, with an incubation of about three days. There are two patterns: the more common abdominal pain with diarrhea, and, in about a third, a prodrome of fever and malaise without diarrhea. The diarrhea can be profuse and turn bloody, the watery-then-bloody course she had. It can also mimic appendicitis, with right lower quadrant pain and fever from terminal ileitis or mesenteric adenitis. Most cases resolve in about a week.

4:29Her illness meets the indications for treating Campylobacter: high fever, bloody stools, bacteremia, or a risk of complications from older age, cirrhosis, pregnancy, or immunocompromise. The drug is a macrolide, azithromycin five hundred milligrams daily for three days, because fluoroquinolone resistance is rising worldwide. Her empiric azithromycin is already the right drug.

4:51Had her culture grown nontyphoidal Salmonella, the decision would have gone the other way. Salmonella causes outbreaks from undercooked poultry, eggs, and vegetables, from pets, with reptiles a classic source, and from person-to-person spread. The risk of invasive disease rises with achlorhydria, immunocompromise, sickle cell disease, schistosomiasis, and ulcerative colitis. About three-quarters of infections are gastroenteritis, resolving within five days. Bacteremia occurs in five to ten percent, particularly in human immunodeficiency virus, HIV, infection, typhoid fever and localized infections in about five percent each, and chronic carriage in under one percent. Colitis is unusual but can persist for weeks.

5:35In a healthy adult with Salmonella gastroenteritis, antibiotics don't improve the outcome and may prolong carriage and add resistance, so they're reserved for severe disease, the extremes of age, immunocompromise, sickle cell disease, prosthetic vascular grafts, bacteremia, or typhoid fever. That list is set by the risk of the infection seeding beyond the gut, not by how many stools there are. Sickle cell disease predisposes to Salmonella osteomyelitis in infarcted bone, prosthetic grafts can be seeded by transient bacteremia into mycotic aneurysms, and immunocompromise blocks the killing of intracellular Salmonella. So a patient with Salmonella is asked about sickle cell disease, a vascular graft, and immune status.

6:18When treatment is indicated, the options are a fluoroquinolone, ceftriaxone, or azithromycin, with sensitivity testing, because resistance is common. Carriage is more likely with gallstones, on which Salmonella forms biofilms, and at the extremes of age.

6:36Shigella reverses the Salmonella rule. Its infectious dose is only ten to one hundred organisms, and it spreads from person to person and through food and water. Its course is biphasic, watery diarrhea from Shiga toxin, then bloody dysentery from invasion, with tenesmus, pain, and fever over five to seven days in adults, and antiperistaltic drugs are avoided because they can prolong it. Antibiotics are indicated in most cases, to shorten illness, shedding, and spread. Because so few organisms cause infection, reducing shedding has an outsize public health benefit, and Shigella doesn't establish a chronic colonic carrier state that antibiotics could prolong. Fluoroquinolones or azithromycin are standard, with resistance common in travel-associated infection. The same healthy woman with Shigella after a trip to South Asia would be treated, though with Salmonella she wouldn't.

7:29Bloody diarrhea without fever points to a different organism. A thirty-four-year-old man ate an undercooked hamburger at a barbecue three days ago and has severe cramping pain and bloody diarrhea without fever, with a colon that looks ischemic on computed tomography, CT.

7:46He most likely has Shiga toxin-producing E. coli, STEC, infection, and severe pain with bloody diarrhea and no fever is its classic clue. STEC, including O157:H7, turns watery diarrhea bloody within one to five days in about eighty percent of patients. Its sources are undercooked meat, classically hamburger, unpasteurized milk and juice, cattle contact, and person-to-person spread, and about forty percent of United States infections are non-O157 strains. On endoscopy and imaging it can mimic ischemic colitis, as his CT does. Its danger is hemolytic uremic syndrome, which develops when Shiga toxin enters the blood and damages the renal endothelium, and which is the leading cause of acute kidney failure in children.

8:36He gets neither antibiotics nor loperamide. Antibiotics lyse the bacteria and release more Shiga toxin, raising the risk of hemolytic uremic syndrome, and loperamide prolongs toxin exposure. His care is supportive, with fluids and monitoring of creatinine, platelets, and hemoglobin. The first patient, with fever and blood, gets azithromycin. He, with blood and no fever, gets no antibiotic, because one would raise his risk of kidney failure.

9:06Some bacteria are dangerous mainly in particular hosts. A fifty-seven-year-old man with hereditary hemochromatosis and cirrhosis ate raw oysters on a beach vacation and cut his shin on rocks while wading the next day. Two days later he's febrile and hypotensive, with a swollen, purple, blistering shin.

9:25He has Vibrio vulnificus infection, with sepsis and necrotizing fasciitis, and his iron overload is why it's so dangerous. Vibrio parahaemolyticus and Vibrio vulnificus are acquired from raw or undercooked seafood, classically raw oysters, and V. vulnificus also enters through wounds exposed to seawater. It causes severe sepsis and necrotizing fasciitis with high mortality, particularly in cirrhosis, hemochromatosis, and other iron overload, because it uses iron as a virulence factor and iron-replete hosts can't contain its spread. He has both ways in, the oysters and the wound, and both reasons it won't stay local.

10:08He's treated immediately with doxycycline plus a third-generation cephalosporin. Doxycycline reaches Vibrio inside macrophages, and the cephalosporin covers the bacteremia and tissue invasion outside cells. Together they kill synergistically in necrotizing fasciitis, where a cephalosporin alone fails.

10:27His iron overload also exposes him to Yersinia enterocolitica, which uses iron the same way, through its yersiniabactin siderophore system. Yersinia causes fever, right lower quadrant pain, and diarrhea lasting up to weeks, with terminal ileitis and bulky mesenteric nodes on CT, so it mimics Crohn disease. It can come with pharyngitis, and it's often followed by reactive arthritis and erythema nodosum. Transmission by transfusion is described, which is why blood banks screen for it. Uncomplicated cases resolve on their own.

11:02Yersinia is treated for bacteremia; for extraintestinal disease, including cellulitis, ophthalmitis, endocarditis, meningitis, osteomyelitis, pneumonia, or abscess; and in special hosts, older adults, diabetics, cirrhotics, the immunocompromised, patients on chemotherapy, and healthcare or childcare workers. Iron-replete patients, with cirrhosis and a high transferrin saturation, hemochromatosis, or transfusion dependence, develop bacteremia that healthy hosts contain. The drugs follow tissue penetration. Aminoglycosides penetrate cells poorly and are reserved for bacteremia, doxycycline and trimethoprim-sulfamethoxazole reach intracellular Yersinia and are preferred for tissue infection, and fluoroquinolones cover the same range by mouth. With cirrhosis and hemochromatosis, he'd be treated even for an illness that resolves alone in others, and terminal ileitis in a patient like him gets a stool culture before anyone calls it Crohn disease.

12:02Pregnancy brings its own organism. A thirty-one-year-old woman, twenty-eight weeks pregnant, has fever, myalgias, and mild diarrhea a week after eating market queso fresco, and her blood cultures grow a gram-positive rod.

12:16She has invasive listeriosis. Listeria monocytogenes is an intracellular gram-positive bacillus carried in soft cheeses, queso fresco, brie, and feta, unpasteurized dairy, deli meats, refrigerated smoked seafood, and raw produce. It grows at four degrees Celsius, which is why food processing is its reservoir. In healthy adults it causes a self-limited febrile gastroenteritis about twenty-four hours after eating it. It invades in pregnancy, in neonates, in older adults, and in the immunocompromised, with HIV, transplant, hematologic malignancy, or chronic steroids, because containing it needs CD8 T-cell immunity, which the Th2 shift of pregnancy, CD4 lymphopenia, or calcineurin inhibitors impair.

13:05In pregnancy, the mother has a flu-like illness while the organism crosses the placenta, causing chorioamnionitis, fetal death, preterm delivery, or neonatal sepsis and meningitis, so her mild symptoms understate the danger to her baby. That's why unexplained fever in pregnancy prompts a food history and blood cultures. Her treatment is intravenous ampicillin, with gentamicin added in severe infection or meningitis for synergistic killing inside cells, and trimethoprim-sulfamethoxazole for penicillin allergy. Cephalosporins don't cover Listeria, which is why empiric meningitis regimens add ampicillin over age fifty and in pregnancy, and ceftriaxone alone would treat nothing in her. Pregnant and immunocompromised patients are advised to avoid the high-risk foods.

13:54Food toxins cause a different illness, recognized by its clock. Preformed toxin syndromes start within hours rather than the twenty-four to seventy-two hours of infection, come without fever, and resolve within twenty-four to thirty-six hours with supportive care, so recognizing them avoids antibiotics and stool studies. A food history asks what was eaten and how many hours later the symptoms began, because the second answer shows whether the toxin was already in the food.

14:21Staphylococcus aureus enterotoxin causes explosive vomiting and diarrhea one to six hours after foods left at room temperature, custards, cream pastries, mayonnaise salads, and cured meats. The toxin is heat-stable, so reheating doesn't help, and it stimulates vagal afferents in the gut, so vomiting dominates and recovery is fast. Picnic guests vomiting three hours after a cream pastry, without fever, are recognized by the timing alone, without cultures or antibiotics.

14:50Bacillus cereus causes two syndromes from two toxins. The emetic syndrome comes one to six hours after reheated fried rice, from preformed cereulide, with vomiting and little diarrhea. The diarrheal syndrome comes eight to sixteen hours after meats and sauces, from an enterotoxin made in the small bowel after the food is eaten. Clostridium perfringens type A causes watery diarrhea and cramps eight to sixteen hours after meat, poultry, or gravy held warm, as the organism sporulates in the bowel and releases enterotoxin, and care is supportive. The slower onset of these last two reflects toxin made after the food is eaten.

15:29A few rarer toxin syndromes each have one clue. Enteritis necroticans, called Pigbel, is caused by the beta-toxin of Clostridium perfringens type C when intestinal protease activity is low, after chitterlings in the United States or traditional pig feasts in Papua New Guinea. Protease inhibitors in the food stop trypsin from inactivating the toxin, which causes transmural necrosis of the small bowel, and unlike the others it needs antibiotics and often resection.

15:58Ciguatera comes from large reef fish, barracuda, grouper, snapper, and amberjack, carrying a heat-stable ciguatoxin from dinoflagellates that activates sodium channels. It causes GI symptoms within six hours and the pathognomonic cold allodynia, in which cold feels burning hot, along with paresthesias, weakness, bradycardia, and hypotension. Care is supportive, with intravenous mannitol historically considered for severe neurologic symptoms.

16:29Scombroid is histamine poisoning from poorly refrigerated dark-meat fish, tuna, mackerel, and mahi-mahi, in which bacteria convert the fish's histidine to histamine. Within an hour it causes flushing, headache, palpitations, urticaria, a peppery taste, and GI symptoms. It's treated with H1 and sometimes H2 antihistamines, and its rapid resolution separates it from a true seafood allergy.

16:56Some problems follow these infections after the organism clears. Reactive arthritis follows Shigella, Campylobacter, Salmonella, and Yersinia. Guillain-Barre syndrome follows Campylobacter. Hemolytic uremic syndrome follows STEC and Shigella dysenteriae. Erythema nodosum follows Yersinia and Salmonella. And post-infectious irritable bowel syndrome follows about ten to fifteen percent of bacterial enterocolitis. Ascending weakness weeks after the first patient's Campylobacter would be Guillain-Barre syndrome, and disordered bowel habits months after a negative culture would be post-infectious irritable bowel syndrome, not persistent infection.

17:38Here are the traps the boards set in these patients. Giving ciprofloxacin for travelers' diarrhea from Southeast Asia. Using rifaximin for febrile or bloody diarrhea. Continuing loperamide with fever or blood. Missing the appendicitis-like picture of Campylobacter. Treating uncomplicated Salmonella gastroenteritis in a healthy adult, or withholding antibiotics with sickle cell disease or a vascular graft. Withholding antibiotics in Shigella. Giving antibiotics or loperamide in STEC. And calling STEC ischemic colitis.

18:13For the host-specific bacteria and the toxins, the traps are these. Missing iron overload or cirrhosis as the risk for Vibrio and Yersinia. Treating severe Vibrio with a cephalosporin alone. Calling Yersinia ileitis Crohn disease without a culture. Using an aminoglycoside for Yersinia tissue infection. Using a cephalosporin for Listeria, or forgetting ampicillin in empiric meningitis over fifty or in pregnancy. Giving antibiotics for a preformed toxin, or thinking reheating destroys staphylococcal toxin. Missing cold allodynia as ciguatera, or calling scombroid an allergy. And pairing a sequela with the wrong organism.

18:54So, start to finish. Travelers' diarrhea gets antibiotics for fever, dysentery, moderate-to-severe disease, or illness that stops travel or work: azithromycin after Southeast Asia and increasingly everywhere, ciprofloxacin where resistance is low, and rifaximin only for noninvasive E. coli. Loperamide helps only without fever or blood. Campylobacter gets azithromycin when treatment is indicated. Salmonella gastroenteritis needs no antibiotic unless the host is at risk of seeding. Shigella usually gets antibiotics. And STEC, severe pain and bloody diarrhea without fever, gets neither antibiotics nor loperamide.

19:36Iron overload and cirrhosis invite Vibrio vulnificus, treated with doxycycline plus a third-generation cephalosporin, and Yersinia, which mimics Crohn disease and is treated for bacteremia or in special hosts. Listeria invades in pregnancy, older age, and immunocompromise and needs intravenous ampicillin, with gentamicin if severe, never a cephalosporin alone. Rapid onset without fever means a preformed toxin: staphylococcus and emetic Bacillus cereus at one to six hours, Clostridium perfringens and diarrheal Bacillus cereus at eight to sixteen. Cold allodynia means ciguatera, flushing after tuna means scombroid, and the sequelae are reactive arthritis, Guillain-Barre syndrome after Campylobacter, hemolytic uremic syndrome, and post-infectious irritable bowel syndrome.

20:24Episode four is the parasites.

20:27For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode three of five of chapter thirty-three, and I'll see you in the next one.