GI Infections

who is at risk for GI infections?

young (<5) and old (>74), travelers and campers, immunocompromised, chronic care institutions, and military personnel

what are the three pathogens classes that cause GI infections?

viruses, bacteria, and parasites

which is the leading cause globally of GI infections?

viruses

which viruses affect children 6 months to 2 years

rotavirus and adenovirus

which virus affects all ages?

norovirus

which bacteria cause GI infections?

Shigella spp., salmonella spp., E.coli, S. aureus, C.difficile

which parasites cause GI infections?

entamoeba histolytica, Giardia lamblia, cryptosporidium spp., roundworms, tapeworms

why does acute/watery diarrhea occur in GI infections?

result of altered intestinal motility - less time in the small intestine means less reabsorption of water, premature emptying of the colon, and bacterial overgrowth

what is a typical presentation of GI infections (occurs in 90% of cases)?

acute/watery diarrhea

describe acute/watery diarrhea

< 10 episodes a day, risk of severe dehydration, fecal occult blood test (FOBT) negative, and osmotic (diarrhea stops with fasting)

which agents cause acute/watery diarrhea

E. coli, rotavirus, and V. cholerae

what is secretory persistent/dysentery diarrhea?

Altered ion transport - characterized by large volume (> 1 liter per day) and normal ionic contents and osmolality (plasma)

what is exudative persisten/dysentery diarrhea?

mucous, exudate, or blood in stool - usually due to inflammatory gut disease and likely affects absorption, secretion, and motility functions

which type of diarrhea is less common (<10% of cases)?

persisten/dysentery diarrhea

typical presentation of persistent/dysentery diarrhea

> 10 episodes per day, FOBT +, mild dehydration, possible fevers

which pathogens cause persistent/dysentery diarrhea?

shigella, salmonella, camplyobacter, and clostridium

typical presentation of traveler’s diarrhea:

travel followed by sudden onset watery diarrhea, malaise, anorexia, abdominal cramps, sudden onset watery diarrhea

pathogens that cause traveler’s diarrhea

variable/often unknown, E.coli, shigella, giardia, salmonella, viral causes

onset for traveler’s diarrhea

5-15 days

duration of traveler’s diarrhea

1-5 days

initial management of traveler’s diarrhea

symptomatic control + source control (water, food, etc.) - loperamide 2 mg PO PRN for loose bowel movements

what is the MDD for loperamide in traveler’s diarrhea?

16 mg/day x 2 days

T/F: all patients with traveler’s diarrhea should receive empiric antibiotic therapy

false

which patients should receive antibiotics for traveler’s diarrhea?

high risk individuals

duration of antibiotic therapy in traveler’s diarrhea

1-3 days

antibiotic options for traveler’s diarrhea:

TMP/SMX, fluoroquinolones (norfloxacin, ciprofloxacin), azithromycin, and bismuth subsalicylate

how long can FQs be used for prophylaxis for traveler’s diarrhea?

up to 2 weeks

dose of azithromycin for traveler’s diarrea

1 gram given once

treatment dosing of bismuth subsalicylate for traveler’s diarrhea

524 mg PO q30 minutes

Prophylaxis dosing of bismuth subsalicylate for traveler’s diarrhea

524 mg PO QID with meals and at bedtime (max ~2 weeks)

risk factors for acute viral gastroenteritis “stomach flu”

exposure to contaminated foods/water, immunocompromised

treatment for acute viral gastroenteritis

supportive care and rehydration 💦

prevention of acute viral gastroenteritis

frequent hand washing, washing fruits + vegetables, cooking meat to recommended temperatures.

causative pathogens for acute viral gastroenteritis

rotavirus, norovirus, parvovirus, adenovirus, etc.

pathogens that cause food poisoning

bacterial cause - staph, campylobacter, shigella, salmonella, clostridium

T/F: food poisoning is an acute, self-limiting disease usually within 24 hours

true

treatment for food poisoning

supportive care and anti-motility agents may be appropriate in some patiets

what is there an increasing endemics in the commonity of?

enterotoxic E. coli (0157:H7)

symptoms of enterotoxic E. coli

diarrhea and abdominal cramping, NO blood or pus in stool

where do enterotoxic E. coli outbreaks typically come from?

fast food chain outbreaks

what can occur from enterotoxic E. coli from burgers?

hemolytic uremic syndrome

which types of toxins are produced from enterotoxic E. coli?

heat-labile and heat-stable toxins

T/F: enterotoxic E. coli infections are often self-limiting (24-48 hours)

true

occasional treatments for enterotoxic E. coli

ciprofloxacin 750 mg qd x 1-3 days, rifaximin or azithromycin 1 gram x 1 or 500 mg qd x 3 days, potential vaccine

which agents are CI in enterotoxic E. coli infections?

antimotility agents

define mild water loss

< 5 % of body weight lost, patient is alert and restless, increased thirst, moist to slightly dry mucus membranes, normal/slightly decreased urinary output

define moderate water loss:

6-9% body weight lost, lethargic and restless, low volume status (low BP, high HR), dry mucus membranes, delayed capillary refill, and dark urine

define severe water loss

> 10% body weight lost, drowsy, limp, LOC, bradycardia, cyanotic, skin ‘tenting,’ no urine production

supportive care for watery diarrhea =

rehydration and electrolytes

treatment for mild-moderate water loss

oral replacement (ORT) with hypotonic oral rehydration (glucose ORT, milk, rice ORT, - lyte products, WHO formula)

what drinks are not typically recommended for mild-moderate water loss

juice, soda, sports drinks, tea, ginger ale, broth

treatment for severe water loss or patients unable to use oral forms

IV fluids (NS, LR)

mechanistic options of anti-diarrheals

anitmotility, adsorbents, antisecretory, enzymes, abcterial replacement

when should antimicrobials be used for diarrhea/water loss

case to case basis - reserved for high risk/severe patients

what is the most common microbial cause of health-care associated infections in the US?

clostridium difficile infection (CDI)

what is accountable for 15-25% of antibiotic-associated diarrhea

clostridium difficile infection (CDI)

why is CDI concerning?

associated with unnecessary use of broad-spectrum antibiotics, can lead to recurrences (1 out of every 5), and can lead to life-threatening complications

which life-threatening complciations can CDI cause?

antibiotic-associated diarrhea (20-25%), antibiotic-associated colitis (50-75%), and pseudomembranous colitis (90-100%)

what is pseudomembranous colitis

colon becomes inflamed and can result in toxic megacolon (colon becomes massive dilated and at risk of perforation) ——> colectomy

which strain of CDI is responsible for more sever outbreaks?

NAP1/B1/027

pathogenesis of CDI

exposure —→ travels to the large intestine —> maturation —→ toxin production —→ mucosal injury, intestinal fluid secretion, inflammation, cell death, pseudomembrane formation

how does C. diff get transmitted?

typically fecal-oral

what does toxin A (enterotoxin) do?

damages the epithelium

what does toxin B (cytotoxin) do?

more potent and causes cell death

patient specific risk factors for CDI

age > 65 years, GI surgery, tube feeding, immunocompromised

facility related risk factors for CDI

length of stay, ICU admission, exposure

medication related risk factors of CDI

acid-suppressing agents, chemo, antibiotics

which antibiotics have the highest risk of causing CDI?

clindamycin, cephalosporins (3rd and 4th gen), carbapenems, and FQs

which antibiotics have lower risk of causing CDI?

erythronycin, ampicillin/amoxicillin/pip/taz, tetracyclines

which antibiotics have the lowest risk of causing CDI?

aminoglycosides, vancomycin, metronidazole

clinical data of non-severe CDI

leukocytosis (WBC </= 15 k cells/mL) AND SCr < 1.5 mg/dL

clinical data of severe CDI

leukocytosis (WBC >/= 15k cells/mL) OR SCr > 1.5 mg/dL

clinical data of fulminant CDI

hypotension or shock, ileus, megacolon

manifestations of AB-associated diarrhea without colitis

mild-moderate diarrhea ~ 6 loose bm/day, crampy lower abdomen discomfort, slight lower abdominal tenderness.

manifestations of AB-associated colitis without pseudomembranes

10+ loos bm/day, fecal leukocytes, occult blood, nausea, anorexia, fever, malaise, dehydration, leukocytosis, abdominal distention, tenderness.

manifestations of pseudomembranous colitis

> 10 loose bm/day, fecal leukocytes, occult blood, nausea, anorexia, fever, malaise, dehydration, electrolyte imbalance, leukocytosis, marked abdominal tenderness, distention

what do pseudomembranes look like in the colon?

irregular yellow plaques of necrotic debris with intervening edematous bowel mucosa

clinical diagnosis CDI

typically with history of antibiotic use in past 8 weeks, < 1% present with ileus, colonic distension without diarrhea, and testing should NOT be done on unformed stool unless ileus suspected

diagnostic criteria or CDI

> 3 unformed stools in 24 hours PLUS stool test + for C. diff or toxins OR pseudomembranous colitis diagnosed by colonoscopy

advantages of stool cultures

excellent sensitivity and specificity

disadvantages of stool cultures

slow turn-around time (24-48 hours), no practical identification of a toxigenic isolate, labor intensive and too slow for clinical use

advantages of EIA

identify toxin A and B, rapid, inexpensive, good specificity

disadvantages of EIAs

less sensitive than the cell cytotoxin assay, must repeat test 3 times to rule out infection

what is the gold standard CDI testing

EIA detection of glutamate dehydrogenase (GDH) first and second do cell cytotoxicity assay or toxigenic culture as confirmatory for GDH-positive stool specimens only

advantages of EIA detection + cell cytotoxicity assay or toxigenic culture

more sensitive than EIA and excellent specificity

Disadvantages of EIA detection + cell cytotoxicity assay or toxigenic culture

detection of GDH antigen alone cannot distinguish between toxigenic and non-toxigenic strains, labor intensive process, slow turnaround time (48 hours)

advantages of PCR

identifies toxin A and B, highly sensitive and specific, rapid

disadvantages of PCR

expensive, identifies asymptomatic carriers

management of CDI

avoid use of any concurrent anti-peristaltic agents (loperamide, narcotics), supportive care (hydration, correction of electrolytes), d/c concurrent antibiotic therapy if possible

T/F: repeat stool assays are not warranted during or following treatment of CDI (except re-infection/relapse)

true - 50% of patients have + stool assay for 6 weeks after therapy

IDSA recommended treatment for initial, non-severe CDI

vancomycin 125 mg PO QID x 10 days, fidaxomicin 200 mg PO BID x 10 days, metronidazole 500 mg PO TID x 10 days

IDSA recommended treatment for initial, severe CDI

vancomycin 125 mg PO QID x 10 days or fidaxomicin 200 mg PO BID x 10 days

IDSA recommended treatment for initial, severe, complicated CDI

vancomycin 500 mg PO or NG QID + (metronidazole 500 mg IV 18hr if ileus is present)

when do most recurrent C. diff infections occur?

within 2 weeks of therapy discontinuation

treatment for first recurrence of CDI

same regimen as initial episode

treatment of second recurrence of CDI

vanco tapered, vanco pulsed (125 mg every other day), vanco 125 mg QID x 10 days then rifaximin 400 mg TID x 20 days, fidaxomicin 200 mg BID x 10 days

vanco taper dosing for CDI recurrence

125 mg QID x12-14d, 125 mg BID x 1 week, 125 QD x 1 week, 125 mg QOD for 2-8 weeks

T/F: probiotics are IDSA recommended for CDI

false

which drugs are fully humanized monoclonal antibodies that neutralize the different toxins produced in CDI

actoxumab and bezlotoxumab (Zinplava)

which drug neutralizes C. diff toxin A

actoxumabwh