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 virulence

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 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 heat-labile 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

What is it used to treat?

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)

Used for severe traveler’s diarrhea

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

what are they used to treat?

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

used to treat entamoeba histolytica, giardia, c. diff and others

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”

what is a common example and what does it treat?

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

Paromomycin is a common example that is used for parasitic infections

what kind of infection is paromomycin normally used for

also, what are its unique toxicities

parasitic infections (especially entamoeba histolytica)

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 and virulence for vibrio cholerae

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

AB enterotoxin that increases cAMP and NaCl leading to watery diarrhea

doxycycline MOA and uses

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

used for cholera

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 (free radical formation)

• nitazoxanide (electron transfer)

Cryptosporidium

• nitazoxanide

MOA of nitazoxanide

what is it used for?

interferes with pyruvate:ferredoxin oxidoreductase enzyme dependent electron transfer.

Used in giardia lamblia, cryptosporidium, entamoeba histolytica, and ascaris lumbricoides

presentation and epidemiology of Clostridioides difficile (c. diff)

watery foul smelling diarrhea, commonly after antibiotics because they interrupt with normal gut flora. leukocytosis is common

fecal-oral spore transmission, especially likely if recently in a hospital or taking PPIs

microbio and virulence factors of C. Diff

spore forming, anaerobic, gram positive rod

Toxin A: increases inflammation and fluid secretion

Toxin B: cytotoxic to epithelial cells of the colon

Common complications of C. Diff

pseudomembranous colitis - yellow/white plaques in the colon due to neutrophilic debris and necrosis

• volcano-like eruption of inflammatory material

Toxic megacolon - dilated colon due to colon wall injury

• risk of perforation and death

workup and treatment for c. diff

workup involves stool toxin antigen for toxin a and b

treatment is oral vancomycin, though fidaxomicin and metronidazole are common too

use, MOA, and AEs for oral vancomycin

this is a glycopeptide that inhibits cell wall synthesis by binding to D-Ala-D-Ala peptides

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms)

DOC for C. Diff (although this may be changing)

why might people be moving away from vancomycin?

because it has been used for so long, there are now resistant bacteria producing D-ala:D-lac, or D-Ala:D-ser which vancomycin cannot bind to/block

Fidaxomicin MOA, AEs, and uses

a macrolide that inhibits bacterial RNA polymerase by inhibiting the initial separation of DNA strands

(acts at an earlier step than rifamicin)

used in drug resistant c. diff

presentation and epidemiology of listeria monocytogenes

in healthy patients, it is usually self limited, involves mild gastroenteritis and other common GI symptoms

in pregnant patients, there is an increased risk for bacteremia and meningoencephalitis, and can result in fetal loss

commonly foodborne from deli meats, milk, soft cheeses.

lysteria monocytogens microbio

gram positive rod with many flagella causing it to have tumbling motility.

Grows in colder temps (50 degrees) and can live intracellularly

virulence factors of lysteria monocytogens

internalin helps it gain entry into cell

Listeriolysin O and phospholipases allow it to escape from intracellular vacuoles

Actin assembly inducing protein helps it move from cell to cell

treatment for lysteria monocytogens

IV ampicillin (a broad spectrum antibiotic)

explain penicillinases and penicillin resistant penicillins

normally, penicillins destroy bacteria by binding to penicillin binding protein (PBP)

bacteria can produce the enzyme penicillinase which destroy penicillins by cleaving their beta lactam ring

beta-lactamase inhibitors act as a decoy drug that bind to the active site of penicillinases, thus blocking their activity

presentation and epidemiology of tropheryma whipplei (whipple’s disease)

presents with multi-system issues, commonly including endocarditis, arthralgias, malabsorption, neurologic symptoms, abdominal pain, and weight loss

rare but serious. more common in farmers and exposure to animals and soil

microbio and histo of tropheryma whipplei

gram positive intracellular rod that is PAS positive

caused by abundance of bacteria-laden macrophages in the lamina propria

workup and treatment of whipple’s disease

fecal fat might be a clue on sudan stain but it is so rare that you may consider other diagnoses first

best diagnostic method is PAS staining from an EGD
treat with penicillin or ceftriaxone, followed by TMP-SMX

MOA, uses, and warnings of ceftriaxone

this is a cell wall synth inhibitor in the 3rd gen cephalosporin class

don’t use with calcium containing solutions due to precipitation hazard

used for whipple’s disease

Explain the MOA and AEs of bactrim (sulfamethoxazole (SMX) and trimethoprim (TMP))

what bug does it treat?

Folic acid synthesis inhibitors

• SMX mimics PABA in TH4 synthesis

• TMP blocks the last step in TH4 synthesis

Can lead to kernicterus

used for whipple’s disease

presentation and epidemiology of ascaris lumbricoides

has pulmonary phase (dry cough, SOB, lung infiltrates) and intestinal phase (abdominal discomfort, nausea, anorexia, diarrhea)

can also present as SBO if they are large enough

most common worm worldwide. transmission through ingested eggs

tropic/subtropic humid areas, poor sanitation

life cycle of ascaris lumbricoides

eggs are ingested (contaminated food)

then in the small intestine the eggs release larvae which penetrate intestinal wall and go to blood

from there, they move to the lung where they are coughed up and then swallowed back into the GI

presentation and epidemiology of hookworm

Presents with pruritic rash between the toes. has pulmonary phase (mild cough) and intestinal phase (epigastric pain, diarrhea). also presents with iron deficiency anemia

more common in humid areas. larvae penetrate the skin/bare feet

life cycle of necatur americanus

larvae from the soil penetrate the skin and enter the blood

they reach the lungs, are coughed up, and swallowed

in the small intestine, the larvae mature into adults and produce more eggs which are passed in stool

life cycle of ancylostoma duodenale (hookworm)

larvae from the soil penetrate the skin and enter the blood

they reach the lungs, are coughed up, and swallowed

in the small intestine, the larvae mature into adults and produce more eggs which are passed in stool

presentation and epidemiology of strongyloides stercoralis (threadworm)

presents with a pruritic rash between toes. has pulmonary and intestinal phase.

can lead to autoinfection

also can cause larva currens which is when the larvae move through the subcutaneous skin (horrifying imo)

typically in hot humid regions and penetrates bare feet

life cycle of strongyloides stercoralis, also include autoinfection

larvae in soil penetrate skin and enter the blood

then they reach lungs and are coughed up, swallowed, and mature in the small intestine

they can either go back to the lungs for autoinfection

or they can be pooped out

presentation and epidemiology of trichuris trichiura (whipworm)

loose stools that may have blood or mucus

rectal prolapse is the big clue

more common from tropical regions

trichuris trichiura morphology

long whip shaped worm (anterior part is actually the thin whip section)

eggs are barrell or football shaped with hyaline plugs on both ends