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
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
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
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
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
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
- 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%)
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
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
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)
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)