Managment of C difficile: the beginnings of Microbiome Management Flashcards
1
Q
epidemiology of C. diff
A
- Anaerobic gram-positive spore-forming bacillus
- Found in >50% of healthy infants and part of normal colonic flora of 5-10% of healthy adults
- 20-40% of pts hospitalized for >2 days (and >50% of those in LTCFs) become colonized with C diff, now leading cause of nosocomial diarrhea in US with 15% mortality in elderly.
- NAP1/BI/027 strain: epidemics, increased toxin production, lower cure and higher recurrence rates
- Now also seeing increase in peripartum, IBD, cirrhosis, organ transplant, chemotherapy patients
- Many of us are colonized by C. diff
- You see it in anyone who is immunosuppressed
2
Q
increase in C. diff-related hospitalizations, US
A
- Doubled between 2001 and 2010. 5.6 in 2001 to 11.5 in 2010.
- President’s Fiscal Year 2014 Budget
- For FY 2014: HIV/AIDS domestic research = $23.2B with 17,000 deaths in 2012 (latest data) = $1,352,941. (million) per patient death from HIV/AIDS
- For FY 2009 (latest info available) C. diff domestic research = $37.5M with 50,000 deaths in 2012 (latest data) = $750.00 per patient death from CDI
3
Q
why do we get C. diff
A
- Infection requires both: alteration of the normal microbiome (usually due to Abx), exposure to organism (usually in a health care facility)
- All antibiotics have been associated with CDI
- Transmission: fecal → oral, person to person
- Once ingested, they germinate in small bowel, multiply in colon and cause inflammation / colitis.
- Spores can survive in environment for days/months and are resistant to common hospital disinfectants.
4
Q
biome cloud
A
- Humans emit 106 biological particles/hour
- Studied in ‘sanitized climate chamber’ for 2-4 hrs
- “An occupied space is microbially distinct from an unoccupied one, and individuals occupying a space emit their own distinct personal microbial cloud”
- Using 16 s rRNA gene sequencing
5
Q
CDI clinical manifestations
A
- Asymptomatic colonization (60-65%) - 6x higher risk of subsequent CDI in patients colonized at admission (21.8% vs. 3.4%)
- Diarrhea, mild to severe
- Fulminant colitis/toxic megacolon (2-3%)
- Recurrent infection (20-30%)
6
Q
CDI testing methods
A
- GDH produced by C difficile (both toxigenic and non tox strains). Ab cross react with other clostridial species
- Good negative predictive value (95-100%); poor positive predictive value (50%)
- We don’t culture this because its very hard to grow: PCR measures bug parts (DNA) – its super sensitive; A negative PCR is a GREAT NEGATIVE; A positive PCR does NOT mean that you are sick with C. diff. it means that you have been exposed to C. diff at some point.
- EIA = enzyme linked immunoassay – measure toxin which is a marker of bad things
7
Q
New testing modality: PET scan
A
- Prior data that RNs can detect CDI smell with app. 80% sens/spec. Dogs >100x more sensitive
- 2 y/o beagle, 2 month training
- S/S on lab stool samples: 100%
- S/S on ‘walk rounds’: Sens: 86% (12/14 cases), Spec: 97% (246/257 controls), 20% of the ‘false pos’ actually got
8
Q
current guidelines: prevention
A
- Greater antibiotic stewardship
- Isolation (when available), cohorting when not (? increased recurrence rates)
- Hand Hygiene / Contact Precautions
- Neither recommends screening of asymptomatic patients or staff, or Rx of asymptomatic carriers.
- Although “moderate evidence” that probiotics (particularly Lactobacillus GG and Saccharomyces boulardii) diminish antibiotic associated diarrhea, neither recommend their routine use to prevent CDI
- Antibacterial sanitizer DOESN’T WORK ON C DIFF!!! you need soap and water to kill C. diff
- Most probiotics are nonsense and don’t actually have any science
9
Q
current guidelines: treatment
A
- Stop offending Abx if possible, avoid anti-peristaltics
- Empiric Rx appropriate when high suspicion
- Metronidazole 500mg TID x10-14d (mild/moderate)
- Vancomycin 125mg QID x10-14d (severe disease, metronidazole intolerant, pregnant/breastfeeding, or failure to respond 5-7 days)
- No routine post-Rx testing (can stay positive)
- Complicated disease: PO/PR vanco plus IV metro
- Early surgical evaluation for critically ill patients (see next)
- We do NOT regularly check to make sure that their C. diff is gone – the end goal is getting rid of symptoms
10
Q
less invasive surgery
A
- Consensus (and data) that early operative intervention is beneficial in severe disease (defined by: shock, pressors, renal failure, MS changes, lactate >5mmol/l, intubation)
- Traditionally: sub-total colectomy with end-ileostomy
- Case-series (U of Pitt): loop ileostomy with intra-op colon lavage (PEG) and post-op antegrade colonic vancomycin flushes via ileostomy
- Colon preservation in >90% of patients
- Significant↑survival c/w historical controls (19% vs 50%)
- 83% laparoscopic procedure
- 93% had ultimate restoration of GI tract continuity
11
Q
fidaxomicin
A
- 629 CDAD patients randomized to: Fidaxomicin 200mg BID x 10 days; Vancomycin 125mg QID x 10 days
- Primary Endpoint: Clinical Cure (<3 unformed stools x 48hrs); NO DIFFERENCE (ITT 88% vs 86%)
- Secondary Endpoints: Recurrence 28 days: lower with Fidaxomicin (15% vs 25%)
- No difference in safety / AEs
- ? Cost effectiveness – super expensive
12
Q
recurrent disease
A
- 20% after initial Rx
- 40% after 1st recurrence
- 60% after 2 or more recurrences
- Mechanisms of recurrence: ? Persistent spores, ? Impaired host immune response (lower anti-toxin IgG antibody levels in patients with rCDI), Decreased biome diversity, ? Reinfection from environment
- Recurrent disease is a challenging clinical problem (expense of hospitalizations)
- Huge impact on these patients (depressed, lose jobs, debilitated)
13
Q
recurrent disease: current guidelines
A
- Same Rx as prior, unless severe (vanco)
- 2nd recurrence: taper/pulse regimen
- Taper: no data to guide (ACG: “propose a simple cost-effective regimen….125 mg daily pulsed Q3D for 10 doses (Scott Curry, personal communication).”, Vs. the widely used QID -> TID -> BID -> QD regimen, Vs. my anecdotal preference: QID dosing at increasing daily intervals (Q2D, Q3D, Q4D))
- ACG explicitly recommends ‘consideration of FMT’ after third recurrence and after taper (SHEA silent)
- By doing the taper, you are allowing some spores to wake up and then kill them – wait two more days and then kill them again
14
Q
recurrent CDI: forget MORE antibioitics, fix the flora with FMT
A
- Reconstitution of a ‘more normal’ flora is a more logical approach than further flora disruption with additional abx
- “Fecal transplant” or “Fecal Flora Reconstitution” in past; now settled on “Fecal Microbiota Transplant (FMT)”
- Not really a ‘new’ Rx; descriptions in ancient Chinese medicine texts date to the 4th century, and ‘transfaunation’ described in veterinary literature for centuries
- Eiseman (1958): fecal enemas show ‘dramatic’ resolution in 4 cases of ‘pseudomembranous colitis’
- FDA now exercising ‘enforcement discretion’ in patients only with rCDI and full disclosure of ‘unknown risks’
15
Q
engraftment is durable (3 months)
A
- Unlike probiotics (unable to persist in an established gut ecosystem)
- Sequenced samples from FMT study of metabolic syndrome patients. (allogenic vs. autologous FMT)
- Microbiome papers (genus level). Some species. These guys did: Single nucleotide variant (STRAIN level analysis)
- Did not depend on relative abundance between donor and recipient species. Vary by recipient (immune factors)
