Progress in Diagnosing and Treating Clostridium difficile in IBD patients

Alan C. Moss MD, FEBG, FACG, AGAF

Associate Professor of MedicineDirector of Translational Research

Disclosures

• Consultant; Janssen, Theravance, Bayer, Roche

• Research Support; Pfizer, NIDDK, Salix, Shire

Case - 58 yr. old male patient

• Extensive ulcerative colitis since 2005• in remission on mesalamine 2.4g/day

• August 2014 – Diverticulitis• Rx antibiotics for 10 days

• “Flare-up” of colitis; increased mesalamine to 4.8g/d• Stool negative for C.difficile

• Persistent diarrhea, abdominal cramps• Rx prednisone 30mg• PCR test comes back “positive” for C.difficile • Rx Metronidazole

Case - Sigmoidoscopy

Day 5 of metronidazole;

• Still having 4-6 stool /day, cramps

Clinical Dilemmas with C. difficile Infection (CDI) in IBD

C. difficile PCR test results in patients with IBD

Which antibiotic to use in IBD?

Should I stop the immunosuppressants?

Are fecal transplants safe in treating recurrent C. difficile in patients with IBD?

C.difficile Testing in IBD

Conundrum of C.difficile infection (CDI) in IBD

Active IBDC.difficile Infection

DiarrheaAbdominal painAltered microbiomeElevated calprotectinEndoscopic lesions

DiarrheaAbdominal painAltered microbiomeElevated calprotectinEndoscopic lesions

7%

Regnault H, Dig Liver Dis. 2014 Oct 4. pii: S1590-8658Martinelli M, Inflamm Bowel Dis. 2014 Dec;20(12):2219-25

Clinical Specificity of PCR Testing

• Positive predictive value of PCR test for C.diff.;• PPV 42-98% - versus toxigenic culture• ‘clinical’ specificity unclear – colonization vs. infection• PCR detects <10 pg of genomic DNA

• Switch from EIA to PCR testing – doubling of “+” results

• Prevalence of C.diff in 2,500 in-patients with IBD;• 4%+ EIA, 5%+ PCR (9%+ EIA, 13%+ PCR in non-IBD)

Burnham C, Clin Microbiol Rev. 2013 Jul;26(3):604-30Shakir F, Gastroenterol Hepatol (N Y). 2012 May;8(5):313-7Deshpande A, Curr Med Res Opin. 2012 Sep;28(9):1553-60

ELISA in PCR+ Stool Samples in IBD

Lamouse-Smith, J Pediatr Gastroenterol Nutr. 2013 Sep;57(3):293-7

• ? PCR+ / ELISA - samples = colonizers

C.difficile Infection Treatment in IBD

Antibiotics for Severe C.diff Infection in IBD

• 114 hospitalized patients with IBD

• 20 UC patients with severe CDI

• 65% got vancomycin with / or after metronidazole

• Not controlled for UC severity

Horton A, Antimicrob Agents Chemother. 2014 Sep;58(9):5054-9Khanna R, Inflamm Bowel Dis. 2013 Sep;19(10):2223-6

Suggested Approach to C.difficile Infection (CDI) in IBD

Horton A, Antimicrob Agents Chemother. 2014 Sep;58(9):5054-9Khanna R, Inflamm Bowel Dis. 2013 Sep;19(10):2223-6

Issa M, Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.Ananthakrishnan, A, Alim Pharm Ther 2012; 35 (7): 789-795

Determine Disease & Infection Severity*

Vancomycin 125mg QID

Metronidazole for first infectionNon-severe disease

Vancomycin 500mg QID‘Complicated’ disease

• Vancomycin with taper• Fecal transplant

• Rifaximin / Fidoxamicin

Severe disease

Recurrent infection

What is ‘Severe’ CDI with IBD?*

‘Severe’ IBD with CDI

• Serum albumin < 3 g/dL• Haemoglobin < 9 g/dL• Serum creatinine >1.5 mg/dL

• 3-9 fold greater risk of colectomy or death

‘Severe’ CDI

• WBC count of >15,000 cells/mm

• Age >60 years• Temperature > 100.9 F• Albumin <2.5 mg/dl• Pseudomembranes• ICU admission

Zar F, Clin. Infect. Dis. 45:302–307. doi:10.1086/519265Ananthakrishnan, A, Alim Pharm Ther 2012; 35 (7): 789-795

Could a sigmoidoscopy help?

Ben-Horin SJ Crohns Colitis. 2010 Jun;4(2):194-8

Only 13% of patients with CDI and IBD have pseudomembranes

Stop or Increase Immunosuppressants during IBD Flares with CDI?

Escalate or Stop IBD Treatment in CDI?

• IBD experts divided on what to do!

• ECCO retrospective study;• 155 hospitalized patients with IBD and CDI• 77% Rx metronidazole• Risk factors for death, colectomy, megacolon, shock;

>2 immunosuppressants during therapy Albumin <2.5mg/dl

Ben-Horin S Inflamm Bowel Dis. 2011 Jul;17(7):1540-6Ben-Horin S, Clin Gastroenterol Hepatol. 2009 Sep;7(9):981-7

Case – Follow-Up

• Metronidazole changed to Vancomycin• Albumin 2.1, age >60, CRP 58

• Still 4-6BM /day, blood

• Infliximab 10mg/kg infusion• 2-4 BM /day, no blood

• CRP 10

• Discharged on vancomycin taper

• In remission in office 2 weeks later

Thank You