Clostridium Difficile Infection
Clostridium difficile infections are the leading cause of health care-associated infectious diarrhea, posing a significant risk for both medical and surgical patients. Antibiotics can cause or contribute to diarrhea. A major cause of broad spectrum antibiotic- associated diarrhea and colitis is Clostridium difficile infection (CDI) A gram-positive anaerobic spore-forming bacillus, C. difficile spores have been reported to be present in foods such as fresh vegetables, meat, and shellfish. CDI has become epidemic and is associated not only with an increase in incidence and severity, but also an increase in rates of CDI-related morbidity and a four-fold increase in CDI-related mortality between 1999 and 2014 This infection is acquired via transmission of C. difficile spores from individuals with active CDI or those who are asymptomatically colonized and shed spores, individuals who have had contact with CDI patients and carry the spores on their hands, and from spore- contaminated environmental exposure. C. difficile spores are resistant to stomach acid. In the small intestine spores germinate into the vegetative form of the organism and produce exotoxins A and B.
Disruption of the normal intestinal flora is caused by exposure to antimicrobial agents prompting C. difficile growth. Hospital infections are increasing with associated morbidity and mortality. While hospital acquired infections are of great concern, increasing evidence points to community acquired infection. In a study reported in 2014, researchers with Kaiser Permanentein the USA found that the majority of hospitalized patients positive for C. difficile outside the hospital or within the first 72 hours of hospitalization.
Stone reported:" In the USAC. difficile caused infections in half a million patients in a single year. Approximately 29,000 patients died within 30 days of the initial diagnosis. Older Americans are especially vulnerable to this deadly diarrheal infection. Two out of every three healthcare-associated C diff infections occur in patients aged 65 years or older. More than 80% of the deaths associated with C diff infection occurred among Americans aged 65 years or older. More than 100,000 C diff infections develop among residents of US nursing homes each year, making C diff infections among the most serious healthcare complications that affect the nursing home population. Unnecessary antibiotic use and poor infection control practices may increase the spread of C diff within a healthcare facility and from facility to facility when infected patients transfer, such as from a hospital to a nursing home. More than 100,000 C diff infections develop among residents of US nursing homes each year, making C diff infections among the most serious healthcare complications that affect the nursing home population."
In 2007, the U.K. issued national policies for controlling C. difficile infection, which included recommendations to avoid clindamycin and cephalosporins and minimize use of fluoroquinolone, carbapenem and aminopenicillin, along with improved infection prevention and control measures. Fluoroquinolone use was reduced by 50%, while C. difficile infections fell by 80%,The fluoroquinolone antibiotics (Ciprofloxacin, levofloxacin, moxifloxacin) should not be used in office settings and practices for mundane and pedestrian upper respiratory tract infections such as bronchitis or sinusitis, or for urinary tract infections.Oral metronidazole and oral vancomycin have been the primary treatment options for 30 years. Fidaxomicin is superior to vancomycin but comes at a steep cost. Fecal transplants are newer and potentially curative treatment options.
Péchiné et al reported on monoclonal antibody development to treat clostria infection:”Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency.”
Fecal transplant are offered with the hope of rebooting a “normal: microbiome that controls the growth of C. difficile. Staley et al reported on their attempts to use freeze dried fecal flora. “Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research. A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory infection.
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