GI tract infections in IBD: Detection and treatment of Clostridium difficile, CMV and enteric pathogens: Case studies David G. Binion, MD Bruce E. Sands,

GI tract infections in IBD: Detection and treatment of Clostridium difficile,

CMV and enteric pathogens: Case studies

David G. Binion, MD

Bruce E. Sands, MD, MS

Case 2: Severe Pouch Inflammation

• 32 yo woman undergoing a 3 stage colectomy and J pouch reconstruction for refractory ulcerative colitis

• Diagnosed with UC at age 22, maintained on mesalamine, then worsening of disease 3 years ago. Escalation to immunomodulator and infliximab with no improvement

• Colectomy for steroid dependent, poorly controlled disease; end ileostomy (6 months earlier).

• J pouch and diverting loop ileostomy (2 months earlier


• Pt employed as dental hygienist in VA Hospital and domicillary

• Admitted with 2 weeks of worsening rectal discharge, pelvic and abdominal pain; fevers.

• Admitted to surgical service• Exam

– Febrile to 101, tachycardic– Abdomen: distended, hypoactive bowel sounds,

tender– Stenosis at the anal cuff/pouch anastomosis


• What diagnostic tests on admission?• Pouchoscopy• CT scan of abdomen and pelvis

Endoscopic appearance of the J pouch and proximal ileum

Hamlin P J et al. Postgrad Med J 2004;80:233-235

• J pouch with diverting loop ileostomy

• Ileum above J pouch downstream from diverting loop ileostomy


• J pouch with diverting loop ileostomy (contrast passes into the ostomy)

• Dilated bowel loops in diverted, downstream small bowel

• Bowel wall thickening• Ascites


• Stool sample sent from pouchoscopy• C difficile is detected• What are data regarding C difficile infection of

small bowel and J pouch?

Case 2: Severe Pouch InflammationC difficile enteritis: An early complication in IBD

patients following colectomy

• Rare but associated with significant morbidity with mortality rates ranging from 60-83%

• Institutional series of six patients (2004-2006). C difficile enteritis manifested with high volume watery ileostomy output, ileus, fever with leukocytosis. No mortality with prompt diagnosis and therapy

Miller, D.L et al. Arch Surg, 1989; 124: p. 1082.Jacobs, A., et al. Medicine, 2001; 80: p. 88-101.Hayetian, F.D., et al. Arch Surg, 2006; 141: p. 97-9.Lundeen S et al. J Gastroentest Surg 2007; 11:138-142Surawicz C. et al. Am J Gastroenterol 2013; 108: 478-498.

Case 2: Severe Pouch InflammationHow can we treat diverted bowel?

• Oral metronidazole • Intravenous metronidazole • Oral vancomycin • Vancomycin enema • Injection of vancomycin into loop ileostomy• Intravenous vancomycin

Lundeen S et al. J Gastroentest Surg 2007; 11:138-142Surawicz C. et al. Am J Gastroenterol 2013; 108: 478-498.Zuckerbraun B. et al. Ann Surgery 2011; 254: 423-7.


• Metronidazole is rapidly absorbed and will enter distal GI tract after biliary excretion (normal bowel)

• Metronidazole in bloodstream will cross into lumen of inflamed mucosa

• Vancomycin oral delivery will not enter distal, diverted small bowel• Vancomycin enema is effective; strictured anal cuff/pouch

anastomosis made this initially• Injection (lavage) of vancomycin flushes into the afferent limb of

loop ileostomy



• Patient responded to vancomycin flushes into the loop ileostomy• Dilation of the anastomotic stricture allowed for vancomycin enema

therapy to be initiated• Recurrence of C difficile after initial therapy stopped after 2 weeks.• Prolonged vancoymcin used until time of the loop ileostomy

takedown


Case 2: Severe Pouch InflammationLong-term results after takedown of diverting

ileostomy

Case 3: Is this C difficile?

• 38 yo woman with 10 year history of Crohn’s colitis on azathioprine and adalimumab therapy in durable remission becomes sick with first colitis flare in 4 years. C difficile infection at time of diagnosis.

• Patient contacts office with complaint of 10 loose bowel movements per day, nocturnal bowel movements, abdominal pain

• Patient was visiting elderly relative in hospital and long-term care facility over the past month

• It is Friday afternoon. Stool testing cannot be brought to lab until Monday

• What should we do?


• Oral vancomycin is started – 125 mg four times per day

• Patient improves over initial 3 days• Stool sample is brought in while patient is on

therapy, and is negative• How accurate is stool analysis if the patient is on

therapy?

Case 3: Diagnostic Tests for C difficile

GeneTarget Chemistry/Manufacturer Sensitivity Specificity PPV NPV

Gold standard

tcdB Prodesse (Gen-Probe

Prodesse, Waukesha,WI, USA) 77.3 99.2 99.2 99.4 TC

tcdB BD GeneOhm (BDDiagnostics, LaJolla,CA, USA) 96.4 99.1 99.6 91.4 Composite

tcdB Cepheid (Sunnyvale, CA, USA) 97.1 93.0 72.3

99.4 CCCNA

tcdB BD GeneOhm 88.5 95.4 88.5 95.4 TC

tcdB BD GeneOhm 83.6 98.2 89.5 97.1 TC

tcdC FRET 86 97 90 96 TC

tcdB SYBR green 93.3 97.4

75.7 99.4 Composite

tcdB Taqman-FAM 87.1 96.5 60.0 99.2 CCCNA

Sunkesula V et al. Clin Infect Dis. 2013;57:494-500

Pro

port

ion

PC

R p

ositi

veTime to conversion of CDI test to negative while on

therapy by treatment (vanco n=20)


• Nucleic acid testing for C difficile is a major advance in the laboratory diagnosis of CDI, but it cannot be the basis for withholding therapy in situations where pre-test suspicion is high

• Once on therapy, sensitivity of PCR based detection of C difficile decreases rapidly

• Once initiated, commit to treatment. No rationale for retesting for C difficile during initial treatment time period

Surawicz C. et al. Am J Gastroenterol 2013; 108: 478-498.

What’s new in treatment …

Surawicz CM, Brandt LJ, Binion DG et al. Am J Gastroenterol 2013; 108: 478-498.

Metronidazole vs. oral vancomycin for C. difficile:Picking your first therapy:

Surawicz CM, Brandt LJ, Binion DG et al. Am J Gastroenterol 2013; 108: 478-498.

Louie et al. N Engl J Med 364 (5):422-431, 2011.

Fidaxomicin and vancomycin for initialC. difficile infection: 30 day recurrence

Recurrent C difficile in IBD

• Prolonged antibiotic therapy (oral vancomycin)• Fecal microbiome transplant (FMT)

– Associated with IBD flare– Resolution of recurrent CDI in IBD

De Leon L, Watson JB, Kelly CR. Clin Gastroenerol Hepatol 2013; 11: 1036-1038.Zainah H, Silverman A. Case Rep Inf Dis 2012; 2012: 810943

Case 4: Bloody diarrhea in terminal ileal Crohn’s disease

• 66 yo woman with 40 year history of Crohn’s ileitis, who had required an ileocectomy 30 year prior is admitted to the hospital with severe bloody diarrhea, tachycardia, dehydration and abdominal pain.

• No prior history of Crohn’s colitis on colonoscopies. Last colonoscopy performed 2 years prior showed healthy anastomosis, diverticuli.

• Oral mesalamine maintenance therapy• Visits with individuals in hospital and nursing home

regularly. Diaper changing of new granddaughter.

Case 4: Bloody diarrhea in terminal ileal Crohn’s disease

• Physical exam obese abdomen, tender to deep palpation. Tachycardic with HR 110

• On admission CRP 9.65 mg/dl• WBC 20.3, 9% bands

• What is your differential diagnosis?• Which diagnostic tests to perform?

Endoscopic appearance of the colon

• Transverse colon

• Transverse colon

Salmonella enteritidis Source – peanut butter

Endoscopic appearance of C difficile infection

IBD non-IBD

Issa M et al. Clin Gastroenterol Hepatol. 2007;5: 345-51.

Documents

GI tract infections in IBD: Detection and treatment of Clostridium difficile, CMV and enteric pathogens: Case studies David G. Binion, MD Bruce E. Sands,