Internal Medicine Journal Watch – November

Hot off the presses, here is this month’s issue of the Internal Medicine Journal Watch, a joint effort by the faculty and the UT Southwestern Internal Medicine Journal Watch Editorial Board (Purav Mody, Jan Petrasek, Nicoloas Barros-Baertl, Shetal Patel, Jeremy Warshauer, Benjamin Jenny, Vishwanatha Lanka, Brian Davis, Ashish Gupta, Ragisha Gopalakrishnan, and Roma Mehta). Some of this month’s highlights include novel data on an algorithm to predict Hepatocellular carcinoma in Hep C patients, outcomes from strict glucose vs. strict blood pressure control, transfusion goals in sepsis, and a great review on aortic aneurysm & dissections! Other highlights include papers on influenza vaccines in the geriatric population, reviews on MRSA infections, CKD and the incidence of cancer, and of course, the EKG case!

Speaking of Poopulation…

Review of C. diff infection guidelines1

By Ernesto Llano, MS3, UT Southwestern Medical School

Background

  • Gram-positive, spore-forming, bacterium spread via fecal-oral route
  • Non-invasive, toxin-mediated disease
  • Spectrum of disease
    • C diff severity
  • Hospital transmission via surfaces and hand carriage
  • Biggest risk factors are exposure to the antibiotics or the organism
    • Others are IBD, GI surgery, PPIs

Diagnosis

  • Suspect in patients with sudden-onset 3+ loose stools for 2 days, or with 10-15 stools for one day2
  • diff testing should only be done on liquid stool, not formed stool
    • C diff testing
  • PCR is preferred method (99% sensitivity and specificity)
  • Do not repeat test as it leads to false-positives
  • Do not test for cure as can remain positive for a month after cure

Classification

  • Mild-to-moderate: CDI + Diarrhea without criteria for severe or complicated disease
  • Severe: CDI + Diarrhea + serum albumin < 3 g/dl + [WBC >15 OR abdominal tenderness]
    • Toxin A is chemoattractant; albumin is negative acute phase reaction protein and also lost in protein-losing enteropathy.
  • Severe and complicated: AMS, fever >38.5, ileus, WBC >35 or <2, hypotension, abdominal distension, lactate >2.2 mmol/L, end-organ failure
  • Recurrent: CDI within 8 weeks of completion of therapy

Management

  • If PCR test is negative but clinical suspicion is high, proceed with empiric treatment
  • Discontinue all antibiotics (except those for CDI treatment) if possible, due to 3-fold risk of recurrent CDI
  • Mild-to-moderate: 500mg metronidazole PO TID for 10 days
    • About $20 total
    • Consider changing to 125mg vancomycin PO QID if no response after 5-7 days
    • If pregnant, don’t use metronidazole.
  • Severe: 125mg vancomycin PO QID for 10 days
    • About $1,000 total
    • Other option is 200mg fidaxomicin PO BID for 10 days
      • About $2,800 total
  • Severe and complicated:
    • Supportive care
    • Continue oral/enteral feeding to help normalize microbiota
    • CT Abd/Pelvis
    • 125mg vancomycin PO QID + 500mg metronidazole IV TID
    • In ileus or if unable to feed, give vancomycin enemas to ensure colonic delivery
    • Surgical consult (colectomy outcomes are poor, 35-80% mortality)
  • Avoid anti-peristaltic agents as they can obscure symptoms and complicate disease
  • If non-continuous GI tract, use vancomycin enemas (500mg in 100-500ml NS q6h).

Recurrent C. Diff

  • 10-20% of diff recurs. After 1 recurrence, 40-65% chance of further recurrences.
  • Causes:
    • Impaired immune response (lower levels of IgG against toxin A)
    • Disturbed microbiota3
      • C diff recurrence
  • Current guideline is to retreat with same regimen (unless metronidazole was used, in which case it should be changed to vancomycin due to toxicity)
  • For second recurrence, guideline is to try more complicated vancomycin regimens like pulsing and tapering
  • Fecal microbiota transplant (FMT) is an experimental technique that thus far appears to be safe and effective for the treatment of recurrent CDI. Current guidelines suggest FMT with 3 or more CDI recurrences.
    • Restore normal microbiota
    • Successfully delivered through many routes (nasogastric, nasoduodenal, EGD, colonoscopy, enema, capsules)
    • Systematic review found overall cure rate of 92%4
    • Found to be 89% effective against 027 virulent strain5
    • Recent trial used frozen capsules6
      • Advantages: no donor screening, available in acute situations
      • Population: 3+ recurrences of mild-to-moderate and previous treatment with vancomycin pulse and taper; or 2 episodes of severe CDI requiring hospitalization
      • Donors: Healthy, 18-50, nonpregnant, normal BMI. No PMHx. No antibiotics in past 6 months. Tested for enteric pathogens, hepatitis, HIV, pallidum.
      • Capsule prep: Suspended in NS. Blended. Sieved. Spun down and resuspended to concentrate. Pipetted into capsules. Frozen at -80 degrees. Each capsule made from a single donor.
      • Procedure: Discontinue antibiotics for 2 days. 15 capsules on 2 consecutive days for total of 30 capsules, all from same donor. If patient did not improve, they were retreated with the same protocol.
      • Results: 70% cure after 1 treatment. 90% cure after second treatment. No adverse effects.
    • Needs more investigation of long-term health effects (e.g. autoimmune diseases).
Works Cited
  1. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478-98.
  2. Uptodate: Clostridium difficile in adults: Clinical manifestations and diagnosis
  3. Chang JY, Antonopoulos DA, Kalra Aet al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis2008;197:435–438.
  4. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrentClostridium difficile Clin Infect Dis 2011;53:994–1002.
  5. Mattila E, Uusitalo-Seppälä R, Wuorela Met al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile Gastroenterology 2010;142:490–496.
  6. Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. JAMA. Published online October 11, 2014. doi:10.1001/jama.2014.13875.

Takayasu Arteritis

Background:
  • Chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches
  • Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation
  • Symptoms reflect end organ ischaemia. More acute inflammation can destroy the arterial media and lead to aneurysm formation
Manifestations:
  • Range from asymptomatic disease found as a result of impalpable pulses or bruits, to catastrophic neurological impairment
  • Non-specific features include fever, night sweats, malaise, weight loss, arthralgia, myalgia, and mild anemia
ACR Diagnostic Criteria – 3 of 6 should be positive (sensitivity 90.5%, specificity 97.8%)
  • Age at onset < 40 years
  • Claudication of the extremities
  • Decreased brachial artery pressure
  • BP difference > 10mmHg between arms
  • Bruit over subclavian arteries or abdominal aorta
  • Arteriogram abnormality: narrowing or occlusion of entire aorta, its branches, or large arteries in the extremities. Usually focal or segmental. Not due to arteriosclerosis or FMD.
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Treatment:
  • Medical
    • Mainstay: Glucocorticoids – effectively suppress the systemic symptoms and usually arrest disease progression. Arterial stenosis may reverse, and ischemic symptoms may improve in early cases.
    • Refractory disease:azathioprine, mycophenolate, methotrexate, tocilizumab, or leflunomide and reserve cyclophosphamide for those who have continued disease activity despite those medications
  • Surgical
    • Irreversible arterial stenosis/significant ischemic symptoms: angioplasty v bypass