the b toxin are now present in many hospitals, however, so testing for 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. other stool tests stool leukocyte measurements and stool lactoferrin levels also have been proposed as diagnostic tests, but may have limited diagnostic accuracy. pcr testing of stool samples by real-time polymerase chain reaction is able to detect c. difficile about 93% of the time and when positive is incorrectly positive about 3% of the time. this is more accurate than cytotoxigenic culture or cell cytotoxicity assay. another benefit is that the result can be achieved within three hours. drawbacks include a higher cost and the fact that the test only looks for the gene for the toxin and not the toxin itself. the latter means that if the test is used without confirmation, overdiagnosis may occur. repeat testing may be misleading, and testing specimens more than once every seven days in people without new symptoms is highly unlikely to yield useful information. prevention self containment by housing people in private rooms is important to prevent the spread of c. difficile. contact precautions are an important part of preventing the spread of c. difficile. c. difficile does not often occur in people who are not taking antibiotics so limiting use of antibiotics decreases the risk. antibiotics the most effective method for preventing cdi is proper antibiotic prescribing. in the hospital setting, where cdi is most common, most people who develop cdi are exposed to antibiotics. although proper antibiotic prescribing is highly recommended, about 50% is considered inappropriate. this is consistent whether in the hospital, clinic, community, or academic setting. a decrease in cdi by limiting antibiotics or by limiting unnecessary prescriptions in general, both in an outbreak and nonoutbreak setting has been demonstrated to be most strongly associated with reduced cdi. further, reactions to medication may be severe: cdi infections were the most common contributor to adverse drug events seen in u.s. hospitals in 2011. in some regions of the uk, reduced used of fluoroquinolone antibiotics seems to lead to reduced rates of cdi. probiotics some evidence indicates probiotics may be useful to prevent infection and recurrence. treatment with saccharomyces boulardii in those who are not immunocompromised with c. difficile also may be useful. initially, in 2010, the infectious diseases society of america recommended against their use due to the risk of complications. subsequent reviews, however, did not find an increase in adverse effects with treatment, and overall treatment appears safe and moderately effective in preventing clostridium difficile-associated diarrhea. one study in particular found that there does appear to be a "protective effect" of probiotics, specifically reducing the risk of antibiotic-associated diarrhea (aad) by 51% in 3,631 outpatients, but it is important to note that the types of infections in the subjects were not specified. yogurt, tablets, dietary supplements are just a few examples of probiotics available for people. infection control rigorous infection protocols are required to minimize this risk of transmission. infection control measures, such as wearing gloves and noncritical medical devices used for a single person with cdi, are effective at prevention. this works by limiting the spread of c. difficile in the hospital setting. in addition, washing with soap and water will wash away the spores from contaminated hands, but alcohol-based hand rubs are ineffective. these precautions should remain in place among those in hospital for at least 2 days after the diarrhea has stopped. bleach wipes containing 0.55% sodium hypochlorite have been shown to kill the spores and prevent transmission. installing lidded toilets and closing the lid prior to flushing also reduces the risk of contamination. those who have cdis should be in rooms with other people with cdis or by themselves when in hospital. common hospital disinfectants are ineffective against c. difficile spores, and may promote spore formation, but various oxidants (e.g 1% sodium hypochlorite solution) rapidly destroy spores. hydrogen peroxide vapor (hpv) systems used to sterilize a room after treatment is completed have been shown to reduce infection rates and to reduce risk of infection to others. the incidence of cdi was reduced by 53% or 42% through use of hpv. ultraviolet cleaning devices, and housekeeping staff especially dedicated to disinfecting the rooms of people with c. difficile after discharge may be effective. treatment carrying c. difficile without symptoms is common. treatment in those without symptoms is controversial. in general, mild cases do not require specific treatment. oral rehydration therapy is useful in treating dehydration associated with the diarrhea. medications several different antibiotics are used for c. difficile, with the available agents being more or less equally effective. vancomycin or fidaxomicin by mouth are the typically recommended for mild, moderate, and severe infections. they are also the first-line treatment for pregnant women, especially since metronidazole may cause birth defects. typical vancomycin 125mg is taken four times a day by mouth for 10 days. fidaxomicin is taken at 200 mg twice daily for 10 days. it may also be given rectally if the person develops an ileus. fidaxomicin is tolerated as well as vancomycin, and may have a lower risk of recurrence. fidaxomicin has been found to be as effective as vancomycin in those with mild to moderate disease, and it may be better than vancomycin in those with severe disease. fidaxomicin may be used in those who have recurrent infections and have not responded to other antibiotics. metronidazole (500 mg 3 times daily for 10 days) by mouth is recommended as an alternative treatment only for c. difficile infections when the affected person is allergic to first-line treatments, is unable to tolerate them, or has financial difficulties preventing them from accessing them. in fulminant disease vancomycin by mouth and intravenous metronidazole are commonly used together. medications used to slow or stop diarrhea, such as loperamide, may only be used after initiating the treatment. cholestyramine, an ion-exchange resin, is effective in binding both toxin a and b, slowing bowel motility, and helping prevent dehydration. cholestyramine is recommended with vancomycin. a last-resort treatment in those who are immunosuppressed is intravenous immunoglobulin. monoclonal antibodies against c. difficile toxin a and c. difficile toxin b are approved to prevent recurrence of c. difficile infection including bezlotoxumab. probiotics evidence to support the use of probiotics in the treatment of active disease is insufficient. researchers have recently begun taking a mechanical approach to fecal-derived products. it is known that certain microbes with 7α-dehydroxylase activity can metabolize primary to secondary bile acids, which inhibit c. difficile. thus, incorporating such microbes into therapeutic products such as probiotics may be protective, although more pre-clinical investigations are needed. fecal microbiota transplantation fecal microbiota transplant, also known as a stool transplant, is roughly 85% to 90% effective in those for whom antibiotics have not worked. it involves infusion of the microbiota acquired from the feces of a healthy donor to reverse the bacterial imbalance responsible for the recurring nature of the infection. the procedure replenishes the normal colonic microbiota that had been wiped out by antibiotics, and re-establishes resistance to colonization by clostridioides difficile. side effects, at least initially, are few. fecal microbiota, live (rebyota) was approved for medical use in the united states in november 2022. fecal microbiota spores, live (vowst) was approved for medical use in the united states in april 2023. it is the first fecal microbiota product that is taken by mouth. surgery in those with severe c. difficile colitis, colectomy may improve the outcomes. specific criteria may be used to determine who will benefit most from surgery. recurrent infection recurrent cdi occurs in 20 to 30% of the patients, with increasing rates of recurrence with each subsequent episode. in clinical settings, it is virtually impossible to distinguish a recurrence that develops as a relapse of cdi with the same strain of c. difficile versus reinfection that is the result of a new strain. several treatment options exist for recurrent c difficile infection. for the first episode of recurrent c difficile infection, the 2017 idsa guidelines recommend oral vancomycin at a dose of 125 mg four times daily for 10 days if metronidazole was used for the initial episode. if oral vancomycin was used for the initial episode, then a prolonged oral vancomycin pulse dose of 125 mg four times daily for 10-14 days followed by a taper (twice daily for one week, then every two to three days for 2-8 weeks) or fidaxomicin 200 mg twice daily for 10 days. for a second recurrent episode, the idsa recommends options including the aforementioned oral vancomycin pulse dose followed by the prolonged taper; oral vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days; fidaxomicin 200 mg twice daily for 10 days, or a fecal microbiota transplant. for patients with c. diff infections that fail to be resolved with traditional antibiotic regimens, fecal microbiome transplants boasts an average cure rate of >90%. in a review of 317 patients, it was shown to lead to resolution in 92% of the persistent and recurrent disease cases. it is clear that restoration of gut flora is paramount in the struggle against recurrent cdi. with effective antibiotic therapy, c. difficile can be reduced and natural colonization resistance can develop over time as the natural microbial community recovers. reinfection or recurrence may occur before this process is complete. fecal microbiota transplant may expedite this recovery by directly replacing the missing microbial community members. however, human-derived fecal matter is difficult to standardize and has multiple potential risks, including the transfer of infectious material and long-term consequences of inoculating the gut with a foreign fecal material. as a result, further research is necessary to study the long term effective outcomes of fmt. prognosis after a first treatment with metronidazole or vancomycin, c. difficile recurs in about 20% of people. this increases to 40% and 60% with subsequent recurrences. epidemiology c. difficile diarrhea is estimated to occur in eight of 100,000 people each year. among those who are admitted to hospital, it occurs in between four and eight people per 1,000. in 2011, it resulted in about half a million infections and 29,000 deaths in the united states. due in part to the emergence of a fluoroquinolone-resistant strain, c. difficile-related deaths increased 400% between 2000 and 2007 in the united states. according to the cdc, "c. difficile has become the most common microbial cause of healthcare-associated infections in u.s. hospitals and costs up to $4.8 billion each year in excess health care costs for acute care facilities alone." history ivan c. hall and elizabeth o'toole first named the bacterium bacillus difficilis in 1935, choosing its specific epithet because it was resistant to early attempts at isolation and grew very slowly in culture. andré romain prévot subsequently transferred it to clostridium, binomen clostridium difficile. its combination was later changed to clostridiodes difficile after being transferred to the new genus clostridioides. pseudomembranous colitis first was described as a complication of c. difficile infection in 1978, when a toxin was isolated from people with pseudomembranous colitis and koch's postulates were met. notable outbreaks on 4 june 2003, two outbreaks of a highly virulent strain of this bacterium were reported in montreal, quebec, and calgary, alberta. sources put the death count to as low as 36 and as high as 89, with around 1,400 cases in 2003 and within the first few months of 2004. cdis continued to be a problem in the quebec healthcare system in late 2004. as of march 2005, it had spread into the toronto area, hospitalizing 10 people. one died while the others were being discharged. a similar outbreak took place at stoke mandeville hospital in the united kingdom between 2003 and 2005. the local epidemiology of c. difficile may offer clues on how its spread may relate to the time a patient spends in hospital and/or a rehabilitation center. it also samples the ability of institutions to detect increased rates, and their capacity to respond with more aggressive hand-washing campaigns, quarantine methods, and the availability of yogurt containing live cultures to patients at risk for infection. both the canadian and english outbreaks possibly were related to the seemingly more virulent strain nap1/027 of the bacterium. known