Describe the toxins of C. diff
-toxins A and B (which are particularly overexpressed in the NAP-1/027 strain that lacks a protein known as tcdC whose expression normally downregulates transcription of these toxins)
What are the risk factors for C. diff infection?
-ABX use, especially concurrently
-hospitalization, health-care facilities
-age (most common 65-84 yo)
IBD-increased with CD?
Gastric acid suppression (?)
What ABX use is especially linked to C. diff?
How is C. diff diagnosed?
-clinical suspicion (diarrhea after ABX use) supported by C. diff and/por toxins in stool
-ELISA for toxins A and B (limited sensitivity with frequent false negatives)
What are the main tx options for initial C. diff diarrhea?
-Oral metronidazole 500 mg q8h x 10 d for mild-moderate
-oral Vanco (125 mg q6h x 10d) for severe and pregnant/lactating women
-High dose oral Vanco and IV metronidazole for complicated disease
T or F. Rectal vanco enemas can be given in pts. with ileus, abdominal distention, and anatomic/surgical abnormalities that prevent oral ABX from reaching the colon
How should the 1st recurrence of C diff be tx? 2nd?
1st: same protocol
2nd: oral Vanco
T or F. Metronidazole crosses the placenta and is expressed in breast milk
T. Dont give to either
What are the AEs of Metronidazole?
-Nausea and metallic taste
-facial anomalies in infants if taken during pregnancy
-increased oral and rectal candida colonization in children if passed through breast milk
-peripheral neuropathy of extremities
How does Fidaxomicin work?
It is a macrolide that is bactericidal against C. diff via inhbiitng bacterial RNA polymerases (note that there is no cross-resistance with other antimicrobials, including rifamycin due to different site of action)
Minimal/no activit against gram neg anaerobes, facultative anaerobes, and enterobacterioceae
How well is fidaxomicin absorbed?
poorly; remains in the GI and eliminated in stool
What are the AEs of fidaxomicin?
T or F. In head to head comparison with vanco in groups at high risk for CDI recurrence, fidaxomicin provides a superior clinical response and lower incidence of recurrence