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Case Presentation
Clostridium Difficile
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.
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.
G.R.’S Meds:
Zosyn 2.5gm IV Q 6hTylenol 10gr Po Q 4 H prnPhenergan 12.5mg IV Q 6 H prnIV Fluids With KCl at 120ml/hrCoumadin 2.5mg Po qdLanoxin 0.25mg Po qdASA 81mg Po qd
G.R.’S Meds: (cont’d)
Atenolol 50mg Po qdCardizem(diltiazem) IV for HR > 100
Ensure Plus 1 can tid Vancomycin 125mg Po qid *Bacid 1 Capsule Po tid*Questran(cholestyramine) 1 scoopful*Lactinex 1 tablet po bid*Flagyl(metronidazole) 250mg po tid*
*= Treatment related therapy
Cultures/Studies
Stool Toxin Positive for C. difficile 1/19/02Urine Cx – negative 1/18/02
Treatment Changes
-Discontinue Zosyn-Change Flagyl to 250mg po qid-Discontinue Vancomycin po-Discontinue Questran-Discontinue Bacid
Summary
The patient’s diarrhea gradually improved over a period of several days and the patient was discharged to an ECF
Antibiotic-Associated Diarrhea
-AAD is defined as otherwise unexplained diarrhea that occurs in association with the administration of antibiotics.
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
Spectrum of Findings
• Nuisance diarrhea• Colitis– Abdominal cramping– Fever– Leukocytosis– Fecal leukocytosis– Hypoalbuminemia– Colonic thickening on CT and endoscopic changes
Colitis
www.gicare.com/pated/ eicnclcc.htm
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
Bartlett J, Antibiotic-Associated Diarrhea, N Engl J Med, Vol. 346, No. 5, Jan. 31, 2002
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
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
Pathogenesis
Major Risk Factors for C. difficile infection:
1. Advanced age
2. Hospitalization
3. Exposure to antibiotics
Clostridium Difficile
- Antibiotics most frequently associated with the infection are:
- Clindamycin- Ampicillin- Amoxicillin- Cephalosporins
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
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
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.
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.
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
Clinical Manifestations
-diarrhea -colitis without pseudomembranes -pseudomembranous colitis -fulminant colitis -hyperpyrexia
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.
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.
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)
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.
Bartlett J, Antibiotic-Associated Diarrhea, N Engl J Med, Vol. 346, No. 5, Jan. 31, 2002
TreatmentTable 4. General Guidelines for the Managementof Clostridium difficile–Associated 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.
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.
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
TreatmentTapering Schedule
Week Vanco dose
1 125mg qid
2 125mg bid
3 125mg qd
4 125mg q.o.d.
5 & 6 125mg q 3 dMylonakis E, et al, Clostridium difficile-Associated Diarrhea A Review. Archives of Internal Medicine, Vol. 161, No. 4, Feb. 26, 2001
Treatment
Other Approaches
-Vancomycin with cholestyramine resin (4gm BID)
- Oral Vancomycin 125mg qid, oral rifampin 600mg bid x 7 days
- Saccharomyces cerevisiae (Brewer’s Yeast)_
- IgG infusion at dose of 200 to 300mg/kg