Case Presentation

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Case Presentation

• Clostridium Difficile

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Patient G.R.- 88 yo WM- Previous hospital
admission for pneumonia treated with
piperacillin/tazobactam- Admitted to KMC on
1/17/02 for scrotal edema and diarrhea.
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Physical Exam WD thin, frail confused WM
A O to Person Only Mild Tenderness in RLQ
Scrotal Edema Without erythema Ht
152.4cm Wt 40 Kg IBW 52 Kg
CrCl 21ml/min U/S Revealed Cysts in
Scrotum W/o Testicular Involvement. No Evidence
of Infection.
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G.R.S Meds Zosyn 2.5gm IV Q
6h Tylenol 10gr Po Q 4 H prn Phenergan 12.5mg
IV Q 6 H prn IV Fluids With KCl at
120ml/hr Coumadin 2.5mg Po qd Lanoxin 0.25mg
Po qd ASA 81mg Po qd
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G.R.S Meds (contd) Atenolol 50mg Po
qd Cardizem(diltiazem) IV for HR gt 100
Ensure Plus 1 can tid Vancomycin 125mg Po
qid Bacid 1 Capsule Po tid Questran(cholest
yramine) 1 scoopful Lactinex 1 tablet po
bid Flagyl(metronidazole) 250mg po tid
Treatment related therapy
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Cultures/StudiesStool Toxin Positive for C.
difficile 1/19/02Urine Cx negative 1/18/02
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Treatment Changes -Discontinue
Zosyn -Change Flagyl to 250mg po
qid -Discontinue Vancomycin po -Discontinue
Questran -Discontinue Bacid
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Summary The patients diarrhea
gradually improved over a period of several days
and the patient was discharged to an ECF
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Antibiotic-Associated Diarrhea -AAD is
defined as otherwise unexplained diarrhea that
occurs in association with the administration of
antibiotics.
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AAD Frequency of Complication

• 10-25 of pts treated with amoxicillin/clavulanate
  .
• 15-20 of pts treated with cefixime.
• 2-5 of those treated with other cephalosporins,
  quinolones, azithromycin, clarithromycin,
  erythromycin, and tetracycline.
• 5-10 of pts treated with ampicillin.
• 1 in 10 to 1 in 10,000 treated w/ clindamycin- in
  hospital

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Spectrum of Findings

• Nuisance diarrhea
• Colitis
• Abdominal cramping
• Fever
• Leukocytosis
• Fecal leukocytosis
• Hypoalbuminemia
• Colonic thickening on CT and endoscopic changes

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Colitis
www.gicare.com/pated/ eicnclcc.htm
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Clostridium difficile-Gm ,
spore-forming anaerobic bacillus. -accounts for
approx. 25 of the cases of AAD-accounts for
the majority of cases of colitis associated with
antibiotic therapy.-Causes
300,000 to 3,000,000 cases of diarrhea and
colitis in the U.S. every year
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Bartlett J, Antibiotic-Associated Diarrhea, N
Engl J Med, Vol. 346, No. 5, Jan. 31, 2002
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Clostridium difficile
-Other Causes of AAD -Other enteric pathogens
-Direct effects of antimicrobial
agents -Reduced fecal flora -Other enteric
pathogens -salmonella, -C. perfringens type
A, -Staphylococcus aureus, and possibly -C.
albicans overgrowth
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Clostridium difficile
-Other Causes of AAD -FQ-resistant disease
-Drug effects independent of motility -Effects
of non-antibiotic drugs - Laxatives -
Antacids - Contrast Agents - Antiarrhythmics -
NSAIDs - Cholinergic Agents - Products
containing lactose or sorbitol
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Pathogenesis

• Major Risk Factors for C. difficile infection
• 1. Advanced age
• 2. Hospitalization
• 3. Exposure to antibiotics

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Clostridium Difficile- Antibiotics most
frequently associated with the infection are -
Clindamycin - Ampicillin - Amoxicillin -
Cephalosporins
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Clostridium difficile
Epidemiology-Most cases occur in hospitals or
LTC (rate of 25-60 per 100,000 occupied
bed-days)-incidence in the OP setting is 7.7
cases per 100,000 person-years
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Pathogenesis

• Toxinogenic C. difficile is isolated from stool
  specimens in only 0 to 3 of healthy adults.
• During hospitalization, colonization frequently
  occurs.
• C. difficile forms spores that persist in the
  environment for years and contamination by C.
  difficile is common in hospitals and LTC
  facilities

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Pathogenesis

• Clinical symptoms develop in only about 1/3 of
  colonized patients, and
• asymptomatic colonization with C difficile may be
  associated with a decreased risk for development
  of C. difficile-associated diarrhea.

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Pathogenesis

• -Two factors have recently been shown to
  increase the probability of symptomatic disease
  in patients who acquire C difficile colonization
  in the hospital
• 1. Severity of other illnesses
• 2. Reduced levels of serum IgG antibody to toxin
  A.

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Pathogenesis

• -Clinically significant strain of C. difficile
  that cause disease produce 2 protein exotoxins,
  toxin A, and toxin B.
• -Full tissue damage requires the action of both
  toxins

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Clinical Manifestations

• -diarrhea
• -colitis without pseudomembranes
• -pseudomembranous colitis
• -fulminant colitis
• -hyperpyrexia

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Clinical Manifestations

• -Mild to moderate CDAD is usually accompanied by
  lower abdominal cramping pain but no systemic
  symptoms or physical findings.
• -Moderate to severe colitis usually presents with
  profuse diarrhea, abdominal distention with pain,
  and, in some cases, occult colonic bleeding.

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Clinical Manifestations

• Fulminant Colitis- develops in approximately in
  1 to 3 of patients
• Others hyperpyrexia, chronic diarrhea, and
  hypoalbuminemia with anasarca.
• C difficile may occasionally complicate
  idiopathic inflammatory bowel disease.
• A reactive arthritis occurring 1-4 weeks after
  C. difficile colitis develops in some patients.

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Diagnosis

• -Non-specific laboratory abnormalities
  leukocytosis with left shift and fecal leukocytes
  in about 50-60 of cases.
• Avg peripheral WBC is 12 x 109/L to 20 x 109/L.
• Gram staining of fecal specimens are no value
• Anaerobic culture of stool (takes 2-3 days and
  does not distinguish between toxinogenic from
  nontoxinogenic strains)

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Diagnosis

• Most sensitive and specific test is a tissue
  culture assay for the cytotoxicity of toxin B
  (takes 1-3 days and requires tissue culture
  facilities)- GOLD STANDARD
• ELISA- detects toxin A and/or B in stool. Rapid
  turnaround.
• Stool samples- If results are negative, 1-2
  additional samples should be sent. If first is
  positive, no further specimens are required.

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Bartlett J, Antibiotic-Associated Diarrhea, N
Engl J Med, Vol. 346, No. 5, Jan. 31, 2002
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• Treatment
• Table 4. General Guidelines for the Management
• of Clostridium difficileAssociated Diarrhea
• 1. Isolate the patient.
• 2. Educate personnel to use gloves when in
  contact with patient and for the handling of
  bodily substances.
• 3. If possible, discontinue inciting antibiotic
  therapy and avoid anti-peristaltic and opiate
  drugs.
• 4. Confirm the diagnosis with a test for C
  difficile toxin. If the results of the first
  specimen are negative and diarrhea persists, 1 or
  2 additional stool samples should be sent.

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• Treatment
• 5. If clinically indicated (moderate or severe
  diarrhea, systemic symptoms, significant
  leukocytosis, etc), consider antimicrobial
  treatment against C difficile. If the clinical
  suspicion is high and the patient is severely
  ill, empiric antimicrobial treatment may be
  started awaiting laboratory confirmation.
• 6. Oral metronidazole (250 mg 4 times per day or
  500 mg 3 times per day) for 10-14 d is usually
  adequate.
• 7. Oral vancomycin hydrochloride (125 mg 4 times
  per day) for 10-14 d is indicated for those who
  cannot tolerate oral metronidazole, those in whom
  metronidazole therapy fails, pregnant patients,
  and, perhaps, severely ill patients.

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• Treatment
• 8. The first relapse/recurrence of C difficile
  colitis can be treated with another 10- to 14-d
  course of oral metronidazole or vancomycin
• 9. Therapy of patients with multiple relapses of
  C difficile colitis has not been examined by
  randomized, prospective, controlled clinical
  trials. A tapering course of metronidazole or
  vancomycin for 4-6 wk has been used.
• Adapted from Johnson and Gerding and Fekety.
• Mylonakis E, et al, Clostridium
  difficile-Associated Diarrhea A Review. Archives
  of Internal Medicine, Vol. 161, No. 4, Feb. 26,
  2001

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Treatment Tapering Schedule Week Vanco
dose 1 125mg qid 2 125mg bid
3 125mg qd 4 125mg q.o.d. 5
6 125mg q 3 d Mylonakis E, et al, Clostridium
difficile-Associated Diarrhea A Review. Archives
of Internal Medicine, Vol. 161, No. 4, Feb. 26,
2001
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Treatment Other Approaches -Vancomycin with
cholestyramine resin (4gm BID) - Oral Vancomycin
125mg qid, oral rifampin 600mg bid x 7 days -
Saccharomyces cerevisiae (Brewers Yeast)_ - IgG
infusion at dose of 200 to 300mg/kg
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Bartlett J, Antibiotic-Associated Diarrhea, N
Engl J Med, Vol. 346, No. 5, Jan. 31, 2002