C. Diff Case Study Flashcards
C. Diff learning objectives are to answer the following questions
Identify the prevalence and risk factors associated with C. difficile infections. (Epidemiology)
Identify common symptoms associated with C.difficle infection and identify other infections which present with similar symptoms (Microbiology)
Describe and interpret tests used to diagnose C. diff infections (Biochemistry)
Recommend strategies to prevent the transmission of C. diff (Microbiology)
Diagram a mechanism to explain the underlying cause of patients’ symptoms. (Pathology)
Identify therapeutic options for individuals with C. diff infection and their associated mechanisms of action. (Pharmacology)
C. Diff transmition
Annually, 500,000 Americans die from C. difficile infections (CDI) and many are acquired while in the hospital
C. diff- transmitted fecal-oral route and hospital workers and devices (fomite) may be intermediaries
Acquired through the ingestion of endospores
Increase in incidence and severity possibly due to the emergence of more virulent strains like B1/NAP1/027, which produce more toxin as well as binary toxin.
Risk factor for CDI:
Need exposure to organism and recent course of antibiotics
Carriers: 5-15% of adults, 84% of infants, and 57% of individuals in long term care facilities
Taking an antimicrobial or antineoplastic (anti-cancer b/c of non-specificly kill anything that’s growing rapidly)in the last 2 months: disease has been reported following 1 dose of antibiotics. Virtually every antibiotic is associated but broad spectrum are a particular concern.
Antibiotics diminish healthy bacteria allowing C. diff to multiply and begin producing toxins
Gastric acid suppression- proton pump inhibitor users more likely to develop C. diff infections
Hospitalization (one of most common nosocomial infection)
Immunocompromised or elderly individuals
C. difficile infections frequently reoccur
Symptoms associated with C. difficile infection
Present with fever, abdominal pain, watery diarrhea, and dehydration
Diarrhea is a key clinical feature- 3 or more loose stools for 1-2 days with no blood present
Pseudomembranous colitis
Severe complications include perforation of colon, dehydration, death
Sepsis- inflammation leading to decrease in blood volume
Toxic megacolon becomes so
swollen creating pressure on lungs making breathing difficult
Differential diagnosis
*Diarrhea can be side effect from many antibiotics
*Watery diarrhea is often caused by viruses (rotavirus, Norovirus)
*Bacteria (E. coli 157:H7, Vibrio cholerae, Campylobacter, Salmonella, Shigella, Yersinia, and Clostridium difficile)
*Protozoan (Giardia, Cryptosporidium, and Cyclospora)
*Most if these infections are self-limiting and not life-threatening, but knowing cause is critical for choosing the correct antimicrobial
***Water diarrhea is most associated with CDI
Positive Diagnosis
Positive stool test for toxin
Increased WBC>15,000 cells/mm3
Direct visualization by sigmoidoscopy of pseudomembranous colitis
ELISA (enzyme-linked immunosorbent assay) to test for Toxin A and B, some strains are A-negative, B-positive
*If target substance is present in immobilized sample then peroxidase enzyme generates purple color or can use fluorescence to detect toxin only stable for 2hrs
LIMITATION: Test yields false negatives.
ELISA has low sensitivity (60-80%) so recommending using nucleic acid amplification tests for toxin genes.
GDH is less specific, but more sensitive. Hence, often used as initial screening, followed by another, such as ELISA.
Pseudomembranous colitis composed of neutrophils, dead epithelial cells, and inflammatory debris
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Anaerobic, gram-positive roddifficult to culture
Clostridium form endospores allowing for stability outside of the host in the soil
Clostridium produce more toxins than any other bacterial genus
Pathology
Normal microbiome suppresses C.diff growth
If microbiome is killed C. diff activated, toxins expressed
Both exotoxin A and exotoxin B bind receptors in the colon walls and are glucosyltransferases that glucosylate RhoGTPase leading to the depolymerization of actin and death of enterocytes.
Toxin A (enterotoxin) activates the inflammatory cascade and disrupts the intercellular tight junctions causing fluid secretion, mucosal injury, edema, and inflammation.
Toxin B (cytotoxin) disrupts the cytoskeleton, leading to mucosal injury and activation of the inflammatory cascade.
Inflammation results in fever, watery diarrhea, increase in white blood cells
Prevention of spread
*Some of the EPA approved hospital disinfectants do not kill C. diff spores even though they said they did on the labels
*Alcohol-based disinfectants are not effective against spore forming bacteria.
- *Decontamination**- occurs prior to sterilization doesn’t remove microbes but removes chemicals, radioactivity to make safe to handle
- *Sterilization**- destroys all living organisms, viruses, and endospores so they are no longer able to reproduce
- *Disinfectant**- reduce organisms to a low enough level that disease is unlikely; inanimate objects since often too toxic to use on human tissues
- *Antiseptic**- microbicide safe to use on human tissue
- *Sanitizer**- decrease number of microbes to a safe level but doesn’t eliminate
- *Aseptic**- procedure performed under sterile conditions
