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Flashcards in Sweatman - Tx for C. diff Deck (11):
1

What strain of C. diff has esp. INC virulence? Why?

- NAP 1/027: lacks tcdC protein, whose expression normally negatively regulates transcription and production of AB toxin 

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2

What is the epi of C. diff?

- Leading cause of AB-related diarrhea 

- Most common hospital-acquired infection since 2010

- Mortality 7x rate of all other intestinal infections combined 

1. Emergency of hyper-virulent strain assoc with rise in disease severity and mortality 

3

What are the risk factors for C. diff?

- Exposure to any antimicrobials, esp. when used in multiple; most commonly with: 

1. Clindamycin, penicillins 

2. Cephalosporins, floroquinolones  

- Hospitalization and other healthcare settings 

- Age: most common in 65-84 y/o's 

- IBD: INC incidence parallels that of CD 

- Gastric acid suppression: not so straightforward link

1. Recent studies suggest PPI's are NOT a risk factor 

4

How is C. diff diagnosed?

- Clinical suspicion: usually diarrhea in pt with current or recent AB use 

1. Supported by toxigenic C. diff or associated toxins in stool 

- EIA's (immuno-assays) to detect A and B toxins: rapid (2-4 hrs), relatively inexpensive, & convenient, but limited sensitivity w/freq false negative results 

1. More sensitive tests under evaluation as alternatives to toxin EIA's 

5

What are the key points for C. diff tx?

- DOC: oral Metronidazole q8h x 10d for mild-mod 

1. PO Vanc q6h x 10d for severe disease, and pregnant/lactating women 

- COMPLICATED DISEASE: high-dose PO Vanc and IV Metronidazole 

- Rectal Vanc enemas can be given in pts w/ileus, abdominal distention, and anatomic/surgical abnormalities that prevent oral AB's from reaching colon 

- Tx 1st recurrence w/same protocol; 2nd w/PO Vanc in extende tx course 

6

What are the AE's with Metronidazole?

- 10% of pts have nausea, metallic taste 

- Readily crosses placenta -> controversy as to adverse effects in fetus: facial anomalies 

1. PO Vanc in pregnancy 

- Expressed in breast milk: INC oral and rectal Candida colonization and loose stools 

- Peripheral neuropathy (numbness and paresthesias) of extremities after very high doses/prolonged use 

1. Could occur with repeated tx failures, and multiple courses of Metro tx

7

Why Fidaxomicin?

- Macrolide AB: bactericidal against C. diff, incl. some hypervirulent strains 

- INH bacterial RNA polys (via different MOA)

- Minimal/no activity against G- anaerobes, facultative aerobes, and enterobacteriaceae, and limited affect on normal fecal flora 

- No cross-resistance w/other antimicrobials, incl. rifamycin class: different sites of action on RNA poly 

- Minimal systematization after oral admin; almost completely eliminated in stool 

- Comparable pattern/rates of AE's to Vanc: N/V, abdominal pain, GI bleeding (all <12%)

8

Who wins head-to-head in high-risk groups, Fidaxo or Vanc?

- In “head-to-head” comparison w/Vanc in groups at high risk for CDI recurrence, Fidaxomicin provides: 

1. Superior clinical response

2. Lower incidence of recurrence 

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9

How does cost vary in CDI drugs?

- Metronidazole < Vanc << Fidaxomycin 

- IF Fidaxomicin could DEC recurrence rate and lower overall tx costs, INC initial investment may be worthwhile 

10

What is the protocol for fecal microbiota transport?

- RECIPIENT: stop AB's 2-3d prior to transplant 

1. Colonoscopy-like prep to DEC stool volume 

2. Loperamide (anti-diarrheal) after transplant 

- DONOR: no recent AB use + screened for fecal pathogens (extensive "vetting" and testing of donor) 

1. Tested for Hep A, B, C, syphilis, HIV 1 and 2

2. Milk of Mg as softener: makes prep of instillate easier 

- Suspend stool in non-bacteriostatic saline by blender; filter through gauze 

- Instill 60mL via colonoscopy (can also be done via NG tube or gastroscopy) 

11

Does fecal microbiota transport work?

- Appears to be effective 

- Trend towards lower GI instillation 

- No evidence of AE's 

- NOTE: this is a burgeoning field of research, as it is now being tested as a potenital tx for other GI conditions, like UC and Crohn's (IBD)