Clostridium difficile

Treatment - C. diff

- Asymptomatic colonization with C. difficile is common. - Treatment in asymptomatic patients is controversial, also leading into the debate of clinical surveillance and how it intersects with public health policy. - In general, mild cases do not require specific treatment - Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis (CDC) is made to avoid frank sepsis or bowel perforation. - To reduce complications, physicians often begin treatment based on clinical presentation before definitive results are available. - Knowledge of the local epidemiology of intestinal flora of a particular institution can guide therapy. - Oral rehydration therapy (ORT) is useful in retaining fluids during the duration of diarrhea.

Diagnostic Tests - C. diff

- Cytogenic assay- Toxigenic culture, in which organisms are cultured on selective medium and tested for toxin production, remains the gold standard and is the most sensitive and specific test, although it is slow and labor-intensive. - Toxin ELISA-Assessment of the A and B toxins by enzyme-linked immunosorbent assay (ELISA) for toxin A or B (or both) has a sensitivity of 63-99% and a specificity of 93-100%: At a prevalence of 15%, this leads to a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 96%. - Previously, experts recommended sending as many as three stool samples to rule out disease if initial tests are negative. - However, recent evidence suggests that repeat testing during the same episode of diarrhea is of limited value and should be discouraged. - C. difficile toxin should clear from the stool of previously infected patients if treatment is effective. - However, many hospitals test only for the prevalent toxin A. Strains that express only the B toxin are now present in many hospitals, and ordering both toxins should occur. - Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes. - Computed tomography -In a recent study, a patient who received a diagnosis of CDC on the basis of computed tomography (CT scan) had an 88% probability of testing positive on stool assay. - Wall thickening is the key CT finding in this disease. Once colon wall thickening is identified as being >4 mm, the best ancillary findings were pericolonic stranding, ascites, and colon wall nodularity. - The presence of wall thickness plus any one of these ancillary findings is 70% sensitive and 93% specific.

Medications - C. diff

- Metronidazole is the drug of choice, because of lower price and comparable efficacy. - Oral vancomycin (125 mg four times daily) is second-line therapy, but is often avoided due to concerns of converting intestinal flora into vancomycin-resistant organisms. - Vancomycin is the treatment of choice in the following cases: no response to oral metronidazole; the organism is resistant to metronidazole; the patient is allergic to metronidazole; the patient is either pregnant or younger than 10 years of age. - Vancomycin must be administered orally because intravenous administration does not achieve gut lumen minimum therapeutic concentration. - Patients unresponsive to Metronidazole can be placed on 14 days of Vancomycin followed by Rifaximin for another 14 days. - A more recent study showed no difference between vancomycin and metronidazole in mild disease, but that vancomycin was superior to metronidazole for treating severe disease. - In this study, severe disease was defined on a point score: One point each was given for age >60 years, temperature >38.3°C, albumin level <2.5 mg/dL, or peripheral WBC count >15,000 cells/mm3 within 48 h of enrollment. - Two points were given for endoscopic evidence of pseudomembranous colitis or treatment in the intensive care unit. Severe disease was defined as 2 or more points on this score. - The main criticism of this study is that a low, non-standard dose of metronidazole (250 mg) was used instead of (500 mg). - Fidaxomicin has been found to be equally effective as vancomycin - The use of linezolid may be considered. - Drugs used to stop diarrhea frequently worsen the course of C. difficile-related pseudomembranous colitis. Loperamide, diphenoxylateand bismuth compounds are contraindicated: slowing of fecal transit time is thought to result in extended toxin-associated damage. - Cholestyramine, a powder drink (an ion exchange resin), which is occasionally used to lower cholesterol, is effective in binding both Toxin A and B, slowing bowel motility and helping prevent dehydration. - The dosage can be 4 grams daily, to up to four doses a day; however caution should be exercised to prevent constipation, or drug interactions, most notably the binding of drugs by cholestyramine, preventing their absorption. - Cholestyramine is not an anti-infective; it dramatically reduces many of the symptoms of a C. difficile infection, but it is not appropriate to use by itself, as it does not change the infection status. Cholestyramine is usually used in concert with vancomycin. - Powdered banana flakes given twice daily are an alternative to cholestyramine, and allow for stool bulking. Treatment with probiotics ("good" intestinal flora) has also been shown effective. - Provision of Saccharomyces boulardii (Florastor) or Lactobacillus acidophilus twice daily times 30 days along with antibiotics has been clinically shown to shorten the duration of diarrhea. - A last-resort treatment in immunosuppressed patients is intravenous immunoglobulin.

Etiology - C. diff

- The numerous spores formed by C. difficile are resistant to most routine cleaning methods that are used on surfaces (except for diluted bleach). - Spores of these bacteria can remain viable outside of the human body for very long periods of time, and this means that patients in a medical facility are often exposed to situations where they end up accidentally ingesting spores. - Extremely rigorous infection protocols are required in order to decrease or eliminate this risk. - C. difficile infection (CDI) can range in severity from asymptomatic to severe and life-threatening, especially among the elderly. - People are most often nosocomially infected in hospitals, nursing homes, or other medical institutions, although C. difficile infection in the community, outpatient setting is increasing. - The rate of C. difficile acquisition is estimated to be 13% in patients with hospital stays of up to 2 weeks, and 50% in those with hospital stays longer than 4 weeks. C. difficile-associated diarrhea (aka CDAD) is most strongly associated with fluoroquinolones. - Fluoroquinolones are more strongly associated with C. difficile infections than other antibiotics including clindamycin, 3rd generation cephalosporins and beta-lactamase inhibitors. - One study found that fluoroquinolones were responsible for 55% of C. difficile infections. In addition to previous use of antimicrobials, use of proton pump inhibitors [PPIs] is associated with a 2-fold increase in risk for C. difficile infection. - The European Center for Disease Prevention and Control recommend that fluoroquinolones and the antibiotic clindamycin be avoided in clinical practice due to their high association with subsequent Clostridium difficile infections. - Frequency and severity of C. difficile colitis remains high and seems to be associated with increased death rates. Immunocompromised status and delayed diagnosis appear to result in elevated risk of death. - Early intervention and aggressive management are key factors to recovery. - The emergence of a new, highly toxic strain of C. difficile, resistant to fluoroquinolone antibiotics, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin), said to be causing geographically dispersed outbreaks in North America was reported in 2005.

Signs and Symptoms - C. diff

- significant diarrhea ("new onset of > 3 partially formed or watery stools per 24 hour period"), recent antibiotic exposure, colitis (abdominal pain), fever (up to 40.5°C), and foul stool odor.

Clostridium difficile

- species of Gram-positive bacteria of the genus Clostridium that causes severe diarrhea and other intestinal disease when competing bacteria in the gut flora have been wiped out by antibiotics. - Clostridia are anaerobic, spore-forming rods (bacilli). C. difficile is the most serious cause of antibiotic-associated diarrhoea (AAD) and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. - In a very small percentage of the adult population, C. difficile bacteria naturally reside in the gut. - Other people accidentally ingest spores of the bacteria while they are patients in a hospital, nursing home, or similar facility. - When the bacteria are in a colon in which the normal gut flora has been destroyed (usually after a broad-spectrum antibiotic such as clindamycin has been used), the gut becomes overrun with C. difficile. - This overpopulation is harmful because the bacteria release toxins that can cause bloating and diarrhea, with abdominal pain, which may become severe. C. difficile infections are the most common cause of pseudomembranous colitis, and in rare cases this can progress to toxic megacolon, which can be life-threatening. - Latent symptoms of C. difficile infection often mimic some flu-like symptoms and can mimic disease flare in patients with inflammatory bowel disease-associated colitis.Mild cases of C. difficile infection can often be cured by discontinuing the antibiotics responsible. - In more serious cases, oral administration of, + first, metronidazole and - if that fails + second,vancomycin are currently the treatments of choice. - Relapses of C. difficile AAD have been reported in up to 20% of cases.