GI infections notes

What are the causes of what people call food poisoning?

staphlococcus aureus

bacillus cereus

clostridium perfringens

presentation and epidemiology of Staph Aureus

nausea and vomiting within 1-6 hours

foodborne; notable from cold salads, mayonnaise, or cream-filled pastries

microbiology characteristics of staph aureus

gram positive coccus (cluster), catalase positive, coagulase positive

Staph aureus MOA

production of heat-stable enterotoxin binds to 5HT-3 receptors on the vagus nerve in the stomach, leading to stimulation of vomiting center in the brain.

presentation and epidemiology of Bacillus cereus

both emetic (within 1-6 hours) and diarrheal (8-24 hours)

foodborne; especially with rice or other starchy foods

microbio of Bacillus cereus

gram positive, spore forming bacilli that are very heat resistant

grows in oxygen

differentiate bt emetic and diarrheal disease causing virulence factors of bacillus cereus

emetic

• spores in food produce a heat stable toxin - cereulide

• acts on serotonin receptors to stimulate vagus nerve

diarrheal

• ingestion of bacteria leads to production of AB toxin that increases cAMP and thus increases NaCl in the lumen. water usually follows the salt

presentation and epidemiology of clostridium perfringens

watery diarrhea (8-24 hour onset)

foodborne; specifically from gravy (cafeteria), reheated meats, or poultry

microbio of clostridium perfringens

gram positive, spore forming, anaerobic rod

what is the function of enterotoxin in clostridium perfringens

causes diarrhea and cramping

what does it mean that an organism has a lack of invasion?

list some organisms that fit under this category

lack of invasion means that the organism doesn’t enter/damage the intestinal lining. Because of this, the diarrhea is watery

Enterotoxigenic E. Coli and Vibrio cholerae are examples

what does it mean that an organism invades the intestinal epithelium?

list some organisms that fit under this category

this means that the organism enters/damages the intestinal lining. it may not reach the lymph nodes or blood though. These organisms will cause bloody diarrhea, fever, and abdominal cramps

enterohemorrhagic, and enteroinvasive E. Coli, and Shigella are examples

what does it mean that an organism invades the lymph nodes and blood stream?

list some organisms that fit under this category

these organisms enter/damage the intestinal lining, but also go further and reach lymph or blood. They cause fever, diarrhea ± blood, abdominal pain, and may lead to sepsis and bacteremia

Salmonella typhi, yersinia enterocolitica, and campylobacter jejuni are examples

presentation and epidemiology of shigella

starts with dysentery and watery diarrhea that turns bloody and mucoid. can also have tenesmus. symptoms start 1-3 days and last about a week

fecal-oral transmission. occurs in daycares and nursing homes. more common in kids, and in resource limited countries (migrant workers, travel in stem)

also contaminated water and raw vegetables/lettuce

low infectious dose required

describe the microbio of shigella

part of enterobacteriaceae, a family of gram (-) rods

non-motile

these don’t ferment lactose (yellow on macconkey agar), and don’t produce sulfur

compare the different species of shigella

S. dysenteriae: most virulent, produces shiga toxin (which inhibits the 60S ribosomal subunit for protein synthesis)

S. sonnei: most common

ALL shigella will invade the intestines

presentation and epidemiology of nontyphoidal salmonella

watery diarrhea with possible mucus or blood. fever, abdominal pain, nausea. begins in 1-3 days and lasts about a week

foodborne or animal contact

can be from raw eggs or poultry (common), and also reptiles, amphibians, or even live poultry

higher infectious dose

presentation and epidemiology of salmonella typhi

typhoid fever — progressive over several weeks (7-14 day incubation). stepwise fever and headache, the rash macules (rose spots), abdominal pain and possible constipation or diarrhea. Can lead to GI bleed, perforation, or even death. (This is an organism that invades intestine and goes to blood/lymph)

fecal-oral transmission (humans only). more common in overcrowded/poorly sanitized areas. In q stem look for travel to S/SE Asia or southern Africa

describe microbio of salmonella

gram (-) motile rods that produce sulfur (black XLD agar) but don’t ferment lactose (yellow macconkey agar)

key virulence factors for salmonella

encapsulated — Vi capsular antigen in S. typhi helps cause disease by preventing neutrophils from phagocytosing it, and survival inside macrophages

biofilm formation can lead to chronic carriage in the gallbladder

this organism invades the intestinal lining and can move through the mucus layer into peyer’s patches (lymph tissue in small intestine)

what would be a complication of chronic carriage of salmonella in the gallbladder?

if they do form a biofilm around a gallstone, they can increase the risk of gallbladder carcinoma (due to chronic inflammation) and recurrent infections

what is a risk of sickle cell patients with salmonella typhi?

osteomyelitis and bacteremia

splenic infarction can make it difficult for the body to fight off encapsulated organisms

compare S. typhi and nontyphoidal salmonella in terms of presentation and cause

S. typhi has longer incubation period (1-2 wks.) and will have hallmark stepwise fever, rash-macules, GI bleed, and even death. It is only transmitted through humans fecal-orally

Non-typhoidal salmonella has an incubation period of 1-3 days, and is transmitted through raw poultry or reptiles/amphibians. It will have more mild symptoms of diarrhea with possible blood or mucus

presentation and epidemiology of Yersinia Enterocolitica

presents with watery or bloody diarrhea, fever, nausea/vomit. Pseudo-appendicitis due to mesenteric lymph node involvement. incubation is 1-14 days and lasts 10-20 days

associated with pharyngitis

fecal-oral or animal transmission

undercooked pork, milk, water. Also contact with animal/pet feces. more common/severe in children, less common overall

microbio of yersinia enterocolitica. where specifically does it like to go?

gram (-) rod with no lactose fermentation (yellow macconkey agar) and no H2S production

predilection for terminal ileum and right colon

key virulence factors of yersinia enterocolitica

pathogenic iron capture and transport allows it to thrive in iron overload states

presentation and epidemiology of enterohemorrhagic E. Coli (EHEC)

presents with bloody diarrhea and abdominal pain, usually no fever. incubation is 1-7 days and symptoms last about a week

has a low infectious dose and can spread from food or fecal-oral

common food source is undercooked ground beef. can also be from animal contact like cattle, deer, or elk

affects all ages

microbio of E. Coli

gram (-) rod that is lactose fermenting

virulence factors of EHEC

E. Coli is natural in the GI flora, but is pathogenic when it contains virulence associated plasmids (segments of extra DNA incorporated into organism)

can attach to GI epithelium (enterocytes) because of pili

can create shiga-like toxin 1 and 2 (stx-1 stx-2)

explain the impact of shiga toxin or shiga-like toxin 1/2

they cause cell death by inhibiting protein synthesis via binding to the 60S ribosomal subunit

this leads to bloody diarrhea and abdominal cramping

Stx2 and Shiga toxin can cause hemolytic uremic syndrome (HUS) which presents with anemia, thrombocytopenia, and kidney damage/failure

presentation and epidemiology of Enteroinvasive E. Coli (EIEC)

presents with watery diarrhea and dysentery because it invades the intestinal mucosa

what is unique about EIEC compared to other E. Coli strains

it is the only one with positive fecal leukocytes

presentation and epidemiology of campylobacter jejuni

presents with prodrome of high fever and flu-like symptoms, then watery diarrhea and abdominal pain

incubation is 1-7 days and symptoms last about a week

can be directly from contact with animals with diarrhea, or fecal-oral from contaminated water or food like milk and poultry

common in young children and young adults

microbio of campylobacter jejuni

its a gram (-) comma or S shaped rod that has flagella

virulence factors for campylobacter jejuni

cholera-like enterotoxin that secretes NaCl into the bowel lumen, pulling water out with it. causes cramping and diarrhea

also cytotoxins that can help with invasion

key compilations with campylobacter jejuni

guillain-barre syndrome: symmetric ascending neuropathy starting at hands and feet, then muscle weakness, and lastly respiratory paralyzation

Reiter’s syndrome: immune mediated reaction with classic triad of conjunctivitis, urethritis, and arthritis

what is reiter’s syndrome

post-infectious immune mediated reaction with classic triad of conjunctivitis, urethritis, and arthritis

associated with HLA-B27 wbc antigen

what are some of the things that trigger reiter’s syndrome

many of the enteric bacteria including…

• shigella

• salmonella

• campylobacter jejuni

• yersinia enterocolitica

• clostridium difficile

can also be triggered by chlamydia

presentation and epidemiology of entamoeba histolytica

most common cause of dysentery world-wide, though not common in the US

can cause amoebic dysentery which is bloody mucoid diarrhea and cramps, with or without fever

fecal-oral cysts in water. more common in resource limited areas. India, africa, mexico, south/central america. migrant travel of over a month may be related

compare the cyst and trophozoite form of entamoeba histolytica

cyst form is ineffective and survive outside the body. this is what gets ingested to cause disease

trophozoite form is fragile but motile. it invades the bowel (causing bloody diarrhea). can rarely invade blood vessels at extracolonic sites, especially in the liver.

what are the histologic findings for entamoeba histolytica

flask-shaped ulcer

What should your approach be for bloody diarrhea in terms of tests to order

stool culture (looking for shiga toxin from shigella), and shiga toxin assay (looks for Stx in EHEC, not shiga toxin in shigella)

can also do optional fecal leukocyte (actual WBCs in stool) or stool lactoferrin (fecal leukocyte marker) to test for inflammation.

Ova and parasite test (O&P) if concern for amebiasis (bloody stool but lack of fecal leukocytes)

compare between a stool culture and a shiga toxin assay

these are both stool tests. stool cultures look for shiga toxin from shigella, while shiga toxin assay looks for shiga-like toxin from EHEC

what are the causes of bloody diarrhea that warrant treatment with antibiotics?

shigella

salmonella typhi

entamoeba histolytica

what is the cause of bloody diarrhea that you should NOT treat with antibiotics and why?

if a stool shiga toxin assay comes back showing EHEC, don’t do antibiotics because this will increase the risk of HUS

which antibiotics are commonly used to treat bloody diarrhea when needed?

azithromycin, ciprofloxacin, and levaquin

what antibiotics would you use to treat entamoeba histolytica?

metronidazole followed by paromomycin

explain the MOA and AEs of azithromycin

this is a macrolide antibiotic that inhibits protein synthesis by blocking the 50S ribosomal subunit, leading to cell death.

AE: inhibits drug metabolizing CYP-450 enzymes. can lead to prolonged QT and torsade de pointes (twisting of the points)

explain the MOA and AEs of fluoroquinolones

these are DNA synthesis inhibitors that work by inhibiting bacterial DNA topoisomerase and DNA gyrase enzymes

AEs include: tendon damage, QT prolongation, GI upset, increased risk of aortic aneurysm or aortic dissection

this makes them not first line DOC

contraindicated in children and pregnant women

explain the MOA and AEs of nitroimidazoles

this class is a DNA synthesis inhibitor that works by generating free radicals that damage bacterial DNA and cause a loss of helical DNA structure/strand breakage

AEs: disulfram-like reaction with alcohol (vomiting, flushing, headache) and CNS disturbances (seizure, ataxia, dizziness). also nausea, anorexia, bloating, cramping

explain some of the pharmacokinetic properties of Metronidazole/Tinidazole

metabolism through glucuronidation, majority of drug eliminated unchanged in the urine

explain the MOA of aminoglycosides “-mycin”

these are protein synthesis inhibitors that work by inhibiting the 30S ribosomal subunit, leading to cell death.

what kind of infection is paromomycin normally used for

also, what are its unique toxicities

parasitic infections

can cause kidney and ear infections, but these are usually additive (more likely to occur when used with other drugs)

presentation and epidemiology of cytomegalovirus (CMV)

this is more commonly an opportunistic infection that can present with colitis, retinitis, esophagitis, encephalitis, or pneumonitis (CREEP). Can be confused with ischemic colitis, so is diagnosed with colonoscopy and biopsy

HIV patients with CD4<200, reactivation of previous infection, or organ transplant recipients

micro/pathology of CMV

Double stranded DNA herpesvirus. known for its owl-eye inclusions (enlarged nucleus with surrounded clearing. often binucleated)

presentation and epidemiology of vibrio parahaemolyticus

watery diarrhea and possible blood with abdominal cramps, nausea, vomiting, fever

incubation is 7-72 hours and symptoms are about 5 days, but usually self limited.

undercooked seafood, common in japan

microbio of vibrio parahaemolyticus

curved, motile, gram (-) bacterial rod found in marine/coastal environments

presentation and epidemiology of Enterotoxigenic E. Coli (ETEC)

presents with anorexia, abdominal cramps, malaise, fever, nausea/vomiting, watery diarrhea

onset is usually 3-5 days after exposure, and symptoms last 1-5 days

Most common cause of traveler’s diarrhea. commonly from travel to Mexico.

fecal oral transmission through contaminated water

virulence of Enterotoxigenic E. Coli

heat labile toxin which increases cAMP

heat stabile toxin which increases cGMP (similar to what is seen in B. Cereus)

these result in decreased sodium reabsorption and increased Cl in the lumen (water follows)

explain the treatment for traveler’s diarrhea

it is usually self-limited and you don’t treat unless it is really severe or there is a risk factor. in that case, use rifaximin, azithromycin, or ciprofloxacin

Rifamycin MOA

DNA synthesis inhibitors that bind to the bacterial DNA-dependent RNA polymerase, thus blocking RNA transcription

presentation and epidemiology of Enteropathic E. Coli (EPEC)

has watery diarrhea that leads to severe dehydration (poor skin turgor)

spread through fecal-oral and poor sanitation. more commonly in infants/young kids and in resource limited areas

virulence mechanism for EPEC

pili which allow for adherence to host cells

presentation and epidemiology of vibrio cholerae

characteristic mucous flecks in diarrhea (rice water stools), vomiting but no fever, rehydration is critical due to profuse diarrhea

fecal-oral contaminated food and water. can be an epidemic where there is poor sanitation.

shellfish can be sporadic cause

microbio for vibrio cholerae

curved, comma shaped, motile, gram (-) bacteria

AB enterotoxin that increases cAMP and NaCl leading to watery diarrhea

doxycycline MOA

this is part of the tetracycline family so it is a protein synthesis inhibitor. it specifically binds to the 30S ribosomal subunit on the bacteria

presentation and epidemiology of rotavirus

viral cause of acute gastroenteritis leading to watery diarrhea that can lead to dehydration. Unvaccinated kids most common, specifically kids under 2. often spreads to other members of household. especially common in winter months.

incubation is 48 hours, lasts about a week

presentation and epidemiology of norovirus

viral cause of acute gastroenteritis that leads to watery diarrhea, vomiting and is common on cruises or confined spaces

incubation is 1-2 days and lasts about 3 days

presentation and epidemiology of giardia lamblia

fatty diarrhea (steatorrhea), bloating, and gas. can be caused by drinking unfiltered water (camping/hiking)

incubation 7-14 days, lasts 1-4 weeks and can be chronic

considered zoonotic as it can be transmitted by contact with many animals

giardia lamblia microbio

flagellated protozoan parasite, ingested as cyst form and then trophozoite pear-shaped form infects and replicates in the small intestine

presentation and epidemiology of cryptosporidium

worse in immunocompromised patients and can be severe and become chronic. otherwise is self-limited and causes watery diarrhea

classic cause is contaminated water from public swimming pool.

cryptosporidium microbio

intracellular protozoan parasite that infects large and small bowel. acid fast organism

small spheres will be seen on histo directly adjacent to enterocyte surface

compare treatment options for giardia vs cryptosporidium

Giardia

• metronidazole

• nitazoxanide

Cryptosporidium

• nitazoxanide

MOA of nitazoxanide

interferes with pyruvate:ferredoxin oxidoreductase enzyme dependent electron transfer.