Comparing the Efficacy of Antibiotics Vs. Fecal Transplant in the Treatment of Clostridium Difficile Infection (CDI)

This is a curated page. Report corrections to Microbewiki.

Introduction

Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.

By: Yara Awwad

At right is a sample image insertion. It works for any image uploaded anywhere to MicrobeWiki.

The insertion code consists of:
Double brackets: [[
Filename: PHIL_1181_lores.jpg
Thumbnail status: |thumb|
Pixel size: |300px|
Placement on page: |right|
Legend/credit: Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC. Every image requires a link to the source.
Closed double brackets: ]]

Other examples:
Bold
Italic
Subscript: H₂O
Superscript: Fe³⁺

Clostridium difficile infection (CDI) has become a major source of morbidity and mortality at hospitals in recent years. According to the CDC, around half a million Americans suffer from Clostridium difficile infection each year. Studies show that Clostridium difficile infections became more severe, prevalent, and difficult to treat. The infection is caused by the toxins produced by the bacteria Clostridium Difficile and it spreads through spores.

Clostridium difficile bacteria are found around the environment is soil, food, air, water and feces. Some people have C. diff in their large intestine in an inactive, non-infectious form. The bacteria also produces spores that ensure their survival under extreme conditions. If these spores are formed in the colon, they can survive antibiotics and could turn into a pathogenic active form.

Depending on the severity of the Clostridium difficile infection, it can be treated using antibiotics that stop the bacteria from growing. However, some strains are becoming more resistant to antibiotics which is making CDIs harder to treat. If the infection is severe, surgery is usually performed to remove the diseased portion of the colon. Around 20% of the people with C.diff get the infection again. In recurring cases, antibiotic therapy is conducted, but the effectiveness of this treatment has been declining. Recent research suggests that an alternative strategy for treating recurring CDI is fecal microbiota transplant (FMT) has promising results.

Sample citations:

A citation code consists of a hyperlinked reference within "ref" begin and end codes.
To repeat the citation for other statements, the reference needs to have a names: " The lower competition in the intestine due to the absence of gut flora helps the spores to thrive and become more pathogenic. The antibiotics that most lead to CDI include penicillin, Fluoroquinolones, Cephalosporins, and Clindamycin.

The majority of CDI cases occur in people who had recent visits to a health facility. In these places, the most common method of infection spread mainly on hands from one person to another. Other risk factors associated with the development of CDI include advanced age, immunocompromised individuals, and renal diseases. One of the studies indicated that becoming infected with CDI is around 10 times greater in people who are 65 years or older. Women and people who previously had the infection are more likely to be infected. The risk continues to rise with each infection.

Spores are metabolically dormant which means that they are intrinsically resistant to antibiotics and attacks from the host's immune system. Therefore, spores from C .difficile are excreted in feces and spread in food and on surfaces when infected individuals do not wash their hands regularly and carefully. Once spores are shed into the environment, they are also resistant to disinfectants that do not have bleach in them. Therefore, the spores can be easily found on surfaces and equipment at hospitals, nursery homes, and households.

The best methods to prevent the transmission of CDI is by washing hands regularly. Soap and warm water are encouraged to maintain hygiene since most hand sanitizers do not effectively destroy the spores. Cleaning products containing bleach should be used to kill spores off of surfaces and objects. It is also very important to avoid the use of unnecessary antibiotics to maintain the healthy functioning of flora in the intestines and prevent the formation of spores.

Symptoms

Clostridium difficile infection ranges from asymptomatic colonization and mild diarrhea to toxic and life threatening megacolon and the inflammation of the lining of the abdominal. The signs and symptoms of the infections take an average of 5 to 10 days to develop. The symptoms of the mild to moderate CDI include diarrhea around three times a day for at least two consecutive days and mild abdominal cramping and tenderness.

Severe CDI, the colon becomes inflamed and sometimes forms patches of raw tissues that bleed or produce pus. The symptoms of the severe infection include blood or pus in the stool, and watery diarrhea 10 to 15 times a day, which leads to severe dehydration due to the lack/disruption of electrolytes in the body. This can cause blood pressure to drop to abnormally low levels which increases the heart rate. If the dehydration occurs quickly and not enough liquid is supplemented, the kidney function rapidly deteriorates which could result in a kidney failure. Fever, nausea, appetite and weight loss, increased white blood cells count, and swollen abdomen are all common symptoms of CDI.

In some rare cases, the colon will be unable to expel gas and stool causing it to become enlarged (megacolon). If the colon is left untreated, it could rupture and cause the bacteria to enter the abdominal cavity. Moreover, in more extreme cases, extensive damage to the lining of the intestine which could lead in the formation of a hole in the large intestine. This also results in bacteria to be spilled from the large intestine into the abdominal cavity. All the aforementioned cases could eventually lead to life threatening consequences.

Treatments:

The first step to treating CDI is by stopping the administration of any other antibiotics that are not prescribed to treat this infection. The most common/standard way of treating this infection is by taking antibiotics that prevent c. difficile from growing. The antibiotics vancomycin and fidaxomicin are usually used for this purpose. Around 10 percent of the patients do not respond to the antibiotic treatment the first time and approximately 20% of treated patients are reinfected with CDI. In cases of non-respondents or recurrence, treatments are usually conducted either by antibiotics or a fecal microbiota transplant.

Probiotics are also being extensively tested for the preventative nature of the infection. The role of probiotics in CDI is controversial. However, recent studies are providing emerging evidence for their role in the primary prevention of CDIs.

Antibiotics:

For the first recurrence, tapered and pulsed vancomycin are usually used if vancomycin was used for the first treatment. Tapered/pulsed vancomycin is used to target the spores. After germination, a prolonged course of the tapered/pulsed regimen is given to attack the vegitative form of the cells. An alternative antibiotic is fidaxomicin, which has a narrower range than vancomycin and thus causes minimal disruption in the gut flora. Ridinilazole is another antibiotic used in phase two treatment that targets clostridia while causing minimal damage to the flora.

A study conducted by Vickers and colleagues in which patients who tested positive for CDI were split into two groups, a group that receives oral vancomycin and the other receives oral ridinilazole. They studied the sustained clinical response (SCR) which includes a cure at the end of the treatment and no recurrence after 30 days of infection clearance. The results show that ridinilazole exhibited superiority over vancomycin in a sustained clinical response. Therefore, studies show that ridinilazole and fidaxomicin are generally used in first treatments and they show better results in terms of a sustained clinical response when compared to other antibiotics, but their use is limited due to their high costs. These antibiotics are also used if the first treatment with vancomycin fails. However, the use of ridinilazole or fidaxomicin for recurrent CDI is still being studied.

Fecal microbiota transplant (FMT)

Fecal transplant, also known as stool transplant, is an emerging method for treating recurrent CDI. It consists of the infusion of fecal microbiota from a healthy donor into the infected patient. The altered healthy colon microbiota is the main cause of recurrent CDI and the restoration of the healthy flora in the colon is the principle of FMT.

In a study done by Cammarota, they compared the effects of using vancomycin and FMT in the treatment of recurrent CDI. They did this by conducting a randomized controlled clinical trial. Patients were randomly assigned to one of the treatments (standard vancomycin or FMT). Follow Up with patients was conducted 10 weeks after the treatment. The cure of C. difficile infection was defined by the disappearance of diarrhea and two negative stool tests for c. difficile toxins. Recurrence after the treatment is defined by diarrhea at least three times for two consecutive days. Statistical results provided evidence that FMT had a significantly higher efficacy than vancomycin. Overall, 90% of the FMT treatment group were cured while 26% of the vancomycin group were treated.

In another study conducted by Lodberg Hvas and colleagues, they found that FMT is superior to fidaxomicin in treating recurrent CDI. A low hemoglobin level was used as a predictor for the failure of the fecal transplant. FMT delivered by colonoscopy after a short course of vancomycin has higher efficacy than fidaxomicin. In this study, they also found that the resolution rates for vancomycin and fidaxomicin are not statistically significantly different.

Conclusion

Clostridium difficile infection is caused by the formation of resistant spores in the colon of the human intestine. There are several methods for preventing the spread of CDI including personal hygiene specifically washing hands, and limiting the use of antibiotics. CDI is posing a challenge to the health care systems across North America and Europe due to its recurring nature and its severe impact on the gut flora. Several studies have indicated that fecal microbiota transplant is the most recommended treatment for recurrent clostridium difficile infection. Antibiotics had a significantly lower sustained clinical response when compared with FMT.

References

Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2018, Kenyon College.