Case Conference Diarrhea Infinitis

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Case ConferenceDiarrhea Infinitis

• Robin Trotman, D.O.
• 8/30/04

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Diarrhea infinitis

• 85 yo wf with ESRD admitted (8/3) 9d prior to
  consult (8/12). Was initially admitted for MSC,
  diarrhea, and hypotension during HD.
• Recent broad spectrum abx. for permacath
  infection (cefepime).
• Cefepime and vancomycin started on admit, and
  after stool was positive for C.dif (8/4), po
  metronidazole started. Received 7 days.
• Cont. to have diarrhea with persistent
  leukocytosis and abdominal pain. After 7 days of
  PO Metronidazole, vancomycin 125mg was started
  for 1 day. Next day her elevated WBC ct
  persisted. Primary team called CAUSE line for PO
  Vanco 500mg and ID consult was recommended.

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ROS

• Diffuse ab pain-7/10, dull, no radiation
• Up to 10 loose BM/day until 4 days prior to
  consult, and one BM the day prior to consult.
• DeniedN/V/melena/hematochezia/jaundice/
• fever/chills/chest pain/dyspnea
• Currently with good appetite, and diarrhea has
  improved but now with persistent leukocytosis and
  ab. tenderness.

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PMH

• ESRD
• Renal Cell Ca.-s/p left nephrectomy
• Recent Enterobacter permacath infection
  7/04Recent Tequin, Gent, Cefepime- started on IV
  vanco(1 day) and Cefepime(4 days) prior to
  consult. Second line placed after infection,
  subsequently malfunctioned replaced with third
  permacath 8/10.
• DM2
• HTN
• Hyperlipidemia
• CAD-s/p NSTEMI
• Breast Ca.-s/p left mastectomy
• GERD
• NKDA

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MEDS

• ASA
• Insulin
• Metronidazole 500IV Q8h D8
• Prilosec
• Ultram
• Tylenol
• Xanax
• Ambien
• Epogen
• Vancomycin 125mg PO Q6h D1

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Soc Hx

• Lives in NH
• Divorced
• No tob, etoh, illicit drugs

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Physical Exam

• Tm 98.9, Tc 98.2, 121/63 _at_ 114 bpm
• Alert, NAD, mm moist, no jvd, no oral lesions,
  edentulous
• Ht. Regular, tachy, no m/r/g, Lungs clear, left
  IJ permacath clean
• Ab distended, tympanic, diffusely tender to
  palpation, no peritoneal signs, hypoactive BS, no
  masses, no hepato/splenomegaly
• Ext full pain free ROM in all 4, no edema
• Skin no jaundice or lesions seen
• Neuro no defecits noted

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Labs 9/12/04
N-73 B-19 L-2 M-5 E-1
12
40
393
33
38
39
39
131
92
60
4.1
23
AG16
Micro 8/4-C.dif positive and negative stool
cx 8/9-VRE pos. rectal swab All BCx sterile
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KUB1
10
CT1
11
CT2
12
CT3
13
CT4
14
CT5
15
KUB2
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Diagnosis

• Severe C.difficile colitis with possible
  impending toxic megacolon

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Recommendations

• NPO
• KUB
• Metronidazole to 500mg IV q8h.
• Increase Vancomycin to 250mg po q8h
• Add Rifampin 300mg iv bid

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Diagnosis

• Gold Standard is culture and cytotoxin assay on
  fibroblast monolayer. Can detect down to 10pg of
  toxin
• Most commonly done test is EIA-requires 4h,
  acceptable substitute but less sensitive(70-90).
  100-1000pg of toxin needed. 10-30 false
  negative.
• PCR is coming but too sensitive. 30 of pts.
  harbor C.dif.
• _at_Hopkins they use-Glutamate dehydrogenase
  screening test, and if pos., then do cytotoxin
  assay. (99.7 NPV)-Bartlett JG.
• There exists species that are toxin A- and B, so
  make sure that EIA detects both. If EIA is
  negative and clinical suspicion is high, repeat
  EIA.

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Questions

• Relapsing versus severe?
• Are there factors that predispose some
  individuals to more severe colitis?
• Is there an objective means to predict outcome
  with severe C. difficile colitis?
• What are the treatment options for severe C.dif
  colitis?

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• Relapsing is differentiated from severe in that
  relapse occurs after 1-2 weeks of symptom
  resolution following appropriate therapy.

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Predicting severe pseudomembranous colitis

• Toxic Megacolonacute dilation of all or part of
  the colon to 6cm plus systemic toxicity.
• Multiple studies have looked at predictors of
  severe cases.
• Agegt70, comorbid illness, prior antibiotics,
  fever, peritonitis, ileus, recurrent
  disease.(Andrews CN, Canadian Journal of
  Gastroenterology 2003 Jun17(6)369-73)-retrospect
  ive cohort analysis of 153 cases.

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Immune Response

• What are the host factors that lead to the wide
  range of host responses to C.dif.? These can
  range from asymptomatic carriage to fulminant
  colitis, MODS, and death.
• Immune response and the amt of IgG to toxin
  A-carrier state vs PMC.
• The 2000 New England Journal paper by Kyne et.
  al. noted that acquired IgG to toxin A can
  prevent C. difficile diarrhea.

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Immune Therapy

• Reports of success with purified preparations of
  intact unmodified IgG from pooled human
  plasma.(Wilcox MH Journal of Antimicrob
  Chemother. 2004 May53(5)882-4.
• Controlled trials are needed as this was an
  analysis of success stories

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Treatment Vancomycin

• PO Vancomycin 125mg po qid up to 500mg po qid PT.
  No data for escalating dose.
• Colonic levels are gt1000 mcg/ml
• No vancomycin resistance.
• Especially if high risk for not responding, ie.
  Low albumin or ICU.(Fernandez A. J Clin Gastro
  200438414)

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Treatmentother

• Avoid narcotics and implicated abx.
• Isolate pts.
• Replace electronic thermometers
• Anion-binding resins, colestipol and
  cholestyramine (taken 2-3h apart from Vancomycin)
• Reconstitution of the normal gut flora-however
  you

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Surgery

• Often warranted in the most severe cases. Less
  than 1 of positive stool assays.
• As of 1994, only 50 cases of fulminant PMC
  required surgery since the advent of oral
  Vancomycin. (Lipsett, et al, Surgery September
  1994)
• Retrospective review by Lipsett et al looked at
  the surgical interventions for PMC at Johns
  Hopkins Hospital.
• Mean APACHE score was 24(40 mortality) and all
  but one of 13 pts had at least one organ system
  failing and the majority had more than one.

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Surgery

• Total abdominal colectomy is treatment of choice
  in the case of TM or perforation. Multiple
  studies have shown that total colectomy for TMC
  is better than diversional procedure.(Dobson et
  al, Intensive Care Medicine 2003, 291030)
• Intraoperative appearance is not indicative of
  severity, and subtotal colectomy in these toxic
  pts. has poor outcome.
• Rubin, MS, Bodenstein, LE, Kent, KC. Severe
  Clostridium difficile colitis. Dis Colon Rectum
  1995 38350.
• Lipsett, PA, Samantaray, DK, Tam, LM, et al.
  Pseudomembranous colitis A surgical disease?
  Surgery 1994 116491.
• Mandell, 5th ed.

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Surgery

• Rubin et al. Dis. Colon Rectum. April
  1995350-354
• Looked at 710 C. difficile colitis cases. 21 of
  these cases required ICU admit or died (mortality
  rate 67). All 21 cases had scores of 4 or
  greater and only one of the mild cases had a
  score of 4.
• 4 patients went to the OR-2 had total ischemic or
  gangrenous colon, had partial resection, and
  died. The other 2 pts had edema, were not
  resected, and survived.
• 16 patients were treated medically and 11 died.
• No lab value could be used as a predictor, but
  score of 4 or less was a statistically
  significant predictor of survival.
• Our pt scored 6/13.

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CDC Severity Score-Rubin et al. Dis. Colon
Rectum. April 1995