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 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
G.R.’S Meds: (cont’d) Atenolol 50mg Po qd Cardizem(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 1/19/02 Urine 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
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
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 -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 10 9 /L to 20 x 10 9 /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.
Treatment Table 4. General Guidelines for the Management of 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
Treatment Tapering Schedule WeekVanco dose 1125mg qid 2125mg bid 3125mg qd 4125mg q.o.d. 5 & 6125mg q 3 d Mylonakis 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