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The Clostridium Difficile Bacterium (C.diff)

    Jun-06-2008

The gram positive Clostridium difficile bacterium is a disease causing bacterium in humans belonging to the bacterial family Clostridium - the genus responsible for tetanus, botulism and gas gangrene among others. Clostridium difficile is a rod shaped bacterium (bacillus) that is a causative agent for antibiotic associated colitis or clostridium difficile colitis - an infection of the colon. The bacterium is normally found in the colon of about five percent of most human populations as an "endocommensal" or gut bacteria, in such individuals, it exists in the gut without causing major symptoms most of the time but may be triggered into rapid proliferation by certain events. The bacterium is very resistant and almost immune to the action of many common antibiotics - the broad spectrum antibiotics in particular. In the body of most people, the large populations of other friendly bacteria in the gut will not permit this bacterium to proliferate and hence the clostridium difficile bacterium is unable to cause a disorder. The problem arises when individuals are administered antibiotics which kill off vast amounts of the other bacteria in the gut, leaving the Clostridium difficile to proliferate as it is resistant to many antibiotics - this expansion of the population of this bacterium causes colitis and diarrhea. The bacterium is known by other names and is called "C.diff" in short and is believed to be singularly responsible for causing symptomatic illnesses that affects approximately half a million Americans annually, the result is that infection and illnesses caused by this bacterium are on a rise at about ten per cent annually in United States. The disorders that are brought on by the C.diff bacterium can include mild diarrhea to a dangerous form of colitis. The mucosal lining of the gastrointestinal tract is destroyed by toxins from the bacterium, leading to severe problems for the affected person.

The threat from C.diff

Infections caused by the C.diff bacterium are on the rise and the bug is becoming a bigger problem each year - as the fatalities from such infections show. At present, the death rate as a result of C.diff infection is soaring by about thirty five per cent annually. The lethality of the C.diff bacterium was said to have increased by four times from base year 1999 to the year 2004, shown by an increase in death rates that rose from 5.7 per million Americans in 1999 to about 23.7 per million Americans by 2004. The death rate for one year along was a devastating seventeen percent during one hospital outbreak that occurred in Quebec, Canada. Therefore, not only are the numbers of cases rising, but the number of fatalities caused by the bacterium also seems to be on the rise everywhere.

There are many distinct strains of the C.diff bacterium that are circulating in the U.S. population. However, from the new millennium, a single minor strain in the previous population of the bacteria has gone from a being a minor population and has become the most frequently isolated form of the C.diff strain. This frequently encountered strain of the C.diff is called by many different names. The U.S. center for disease control and prevention - CDC, in a reference to its genetic fingerprint, calls it the NAP1 strain. The name of the strain is 027 in Europe and in Canada; it's often the BI strain.

This predominant strain of C.diff called the NAP1 started off by first becoming resistance to the fluoroquinolone based antibiotics used as a bactericidal treatment. In addition, the NAP1 strain may have also acquired some resistance to the anti-microbial compound known as Flagyl, which along with the compound known as vancomycin are the two principal antimicrobial drugs used in treatments.

Aside from the resistance to antibiotics, the NAP1 strain also causes some other problems. Normal strains of C.diff usually give off two toxins in the human body. The volume of toxins released by the NAP1 strain is much more, it releases up to sixteen times more of toxin A and up to twenty three times more of the toxin B - these toxins increase the pathogenic effect and tear down the mucosal lining of the colon. The NAP1 strain additionally produces another toxin, which has been named as the binary toxin, how this specific toxin affects the human host has not been elucidated.

Thirty seven U.S. states and the District of Columbia have reported finding the NAP1 strain in samples taken from patients affected by C.diff.

In the five years from 2000 to 2005, C.diff related illnesses in the United States, accounted for approximately 300,000 hospitalizations annually according to a recent report. This rate of hospitalization is much more than those reported for MRSA, which typically results in about 126,000 Americans being admitted to the hospital annually. Therefore C.diff is considered now to be epidemic in the U.S. With a reported infection rate increasing at ten percent that annually results in hospitalization. However, it is the even faster climb of the death rate caused by C.diff infection that is the cause of the greatest fear at the present time.

Fatalities caused by the pathogen appear to be on the rise, and the fatality rate has been nearly doubling from a 1.2 per cent of all patients affected to 2.2 per cent of all affected on average. In Canada, in the course of a single outbreak in a hospital, the one year mortality rate for C.diff infection was approximately seventeen percent.

Epidemics caused by the C.diff pathogen can be classed into three distinct ongoing epidemics. One that mainly affects patients in hospitals, one that seems to run in the general community and one that primarily affects livestock in farms.

The "Super-bug"

The term "super-bug" has often been applied to many microbes, including the C.diff for its great resistance to many different commonly used antibiotics. However, super-bug as a term is not considered to be scientific. The term 'super-bug" is an invention of the media, who coined the term alluding to the iconic comic character Superman, who was bulletproof and immune. In much the same way, the so called super-bugs are immune to antibiotics and are thus "super" as they have become impervious to all the drugs normally used to kill other germs. The term "super-bug" as a designation is reserved in most dictionaries only for germs specifically resistant to the very drugs that have normally been employed to eliminate them in the body. In a similar vein, the term "super-bug" has in addition been used as a descriptive term for different germs that, like many of the "superheroes" in comics, were initially normal but turned super strong due to some reason. In the case of germs, this simply designates an increase in virulence of a normally almost benign germ.

The resistance to broad spectrum antibiotics is not restricted to NAP1 strain, and all the C.diff strains are variably resistant to many of the classic antibiotics that have been normally employed in the eradication of other microbes. This resistance to antibiotics is the central part of the problem, as the C.diff mostly tends to start affecting individuals whose intestinal flora has been disrupted by prolonged administration of antibiotics. However, in contrast to the NAP1 strain, the majority of the C.diff strains tend to stay sensitive to the antimicrobial drugs flagyl and vancomycin, for this reason, these drugs are usually employed in the treatment of C.diff related problems.

At the same time, the resistance to the fluoroquinolone based antibiotics of the NAP1 strain is far greater than the resistance of the other C.diff strains. Moreover, the NAP1 strain produces twenty times more bacterial toxin than the normal C.diff strains which may leading to a more severe infection. The most pertinent fact is the existence of clinical evidence that the NAP1 form induces a far more severe form of disease in comparison to the other strains of C.diff.

The term "super-bug" has been claimed for the NAP1 strain of C.diff due to these reasons, and while it is called a super-bug in the media, the term is never used in scientific reports made by clinicians.

The causes for the rapid rise of C.diff infections

C.diff infections have shown a fluctuation and the number of hospital patients afflicted by C.diff infection was fluctuating in from 1996 till about 2000. However, the rate and volume of reported C.diff infections showed a steep increase from the year 2000 to 2001. This sudden spurt in cases of C.diff infection continued through 2006 to become one of the new silent epidemics sweeping the modern world. At the present time, some preliminary data that has been gathered suggests that the epidemic of C.diff infections has slowed down a little by the year 2007, though the report needs to be further analyzed.
What is the reason for the sudden spurt of cases at the turn of the millennium? One of the main reasons for the sudden spurt of the C.diff infections states that the NAP1 strain which has been around for three decades, developed fluoroquinolone resistance and became the most prevalent strain of the C.diff bacterium in susceptible populations. The sudden development of this resistance, coupled with the NAP1 strain's production of "hyper-toxin" could be the principal explanation for the sudden spurt of cases.

In a measure of the community level of C.diff infections, a study in 2006 conducted in Connecticut reported that in cases of community acquired C.diff, the disease struck about seven people out of a total of one hundred thousand persons in the community. Out of this, approximately one in four cases would not have the risk factors usually connected with C.diff infection. At the same time, more than a third of these individual cases did not have any exposure to antimicrobial drugs at any time.

If, the use of antimicrobial drugs were not a factor in a third of the cases, the question asked was, where is the C.diff coming from? At community level, it is believed that greater majority of C.diff cases is due to transmission of the bug from one person to another.

C.diff from dietary sources

One of the most troubling findings in recent years is that a few cases of C.diff infections seem to come from food consumed by the person. This could happen due to two distinct reasons.

Canadian clinical researchers in the year 2005 conducted an experiment that studied the possible transmission of C.diff via dietary sources. They purchased fifty three packages of beef and seven packages of veal from five grocery stores in the province of Ontario and Quebec as laboratory samples. These samples were tested in the lab for contamination with the C.diff bacterium, C.diff was detected in one out of every five packages in the study. On further analysis it was found that two-thirds of the C.diff isolates were similar to the NAP1 strain responsible for the most severe form of the condition. The strain of C.diff bacteria that have been isolated from human patients is very similar to bacterial isolates from pigs and cattle - thus, bug affects humans and animals equally. Human isolates of the bacterium can be said to be identical to those isolated from pigs.

Could the strains of this bacterium have been transmitted from animal to human populations? Some evidence at least shows the "migration" of epidemic strains of the bacterium from food producing animals to their present human hosts. One reason could be that animal populations were affected by these bacterial epidemics before the human epidemic even started to affect communities.

At the same time, direct transmission from animals to humans via the food supply forms a miniscule proportion of all affected humans, provided it occurs at all, and to date, no proof of such transmissions exists. Thus, it appears unlikely that the current C.diff epidemic is based solely on animal to human transmission of the bacterium.

At the present time, academic researchers and scientist at the CDC are actively culturing samples of meats sold at retail shops for C.diff contamination. The results from these studies will be out soon and should hopefully address the question of transmission of the C.diff bacterium from food sources. In time, the CDC plans to examine all the dietary risk factors for C.diff infections affecting communities at large.

The great majority of C.diff infections are said to occur via transmission from one person to the other, this will not change even if it is found that C.diff can be acquired from dietary sources.

Mode of infection and transmission

There is a general belief even among the majority of health care professionals that all humans carry C.diff in their intestines as an endocommensal, and that the bacterium becomes a menace when antibiotic therapy or illness disturbs the normal gut ecology leading to a spurt in C.diff population.

This is not true of all individuals, as C.diff colonizes only about five percent of the population, living as an endocommensal. The majority of such individuals with C.diff populations may even be simply suffering from a temporary infection of the bacterium as the five percent infection rate is gleaned from population studies restricted to observations carried out at one point in time.

At the same time, a previous infection of C.diff is apparent at some time in the lives of more than half of all Americans. Such C.diff infections usually take place soon after the birth of the individual. However, most infants are rarely infected with C.diff and its symptomatic disorders. While the underlying reasons for this have still not been worked out, animal models used in studies suggest that the toxins produced by the C.diff bacterium have problems binding to the immature gut and hence cannot cause the disease in infants.

Since all clostridium bacteria are anaerobes (organism that live in places without oxygen), the C.diff bacteria is very sensitive to the presence of oxygen in the environment and will quickly die in an oxygen rich environment. However, the spores produced by the bacterium are successful no matter what. These C.diff spores are almost indestructible and can live on for months together in a desiccated condition on dry surfaces to infect other hosts. One recommendation of the CDC concerning C.diff spore contamination is to disinfect all surfaces near a patient with bleach, as the most commonly used hospital disinfectants will not affect the spores.

Millions of these C.diff spores are found in the feces of people with C.diff infection. The transmission of the bacterium from one person to another is via these spores, which will carry the infection mostly through the fecal-oral route - usually in contaminated water or food. Hands must be carefully washed and rinsed to rid contaminated skin of the spores, the use of alcohol gels as a washing solution may not be sufficient to kill or eliminate the spores from the skin.

C.diff caused disorders usually start to become evident when two things happen to a person.

The initial factor is that the person ingests some C.diff spores in contaminated food or water. The first factor is not sufficient to cause disease; C.diff related problems become acute when ecological balance of the normal gut bacteria living in the colon is disturbed usually through the prolonged use of antibiotics. This leads to the coming of antibiotic associated colitis or diarrhea due to the explosion of the C.diff population in the colon.

Susceptible groups

It has been measured in studies that among hospitalized people who had received some form of antibiotic treatment in the hospital, more than nine out of ten would get C.diff infections.

The use of antibiotics is not the only cause for C.diff infections especially at the community level. Clinical evidence from studies on communities affected by the C.diff epidemic have come up with evidence that thirty to forty per cent of all the community acquired cases of C.diff infection in people, affected individuals who had no current or recent medical issues and who were otherwise healthy in all respects.

C.diff related colitis and diarrhea are mostly related to the use of fluoroquinolone antibiotics in most people affected by C.diff related disease. The chances of developing C.diff related illness is greatest for patients who have been administered multiple types of antibiotics, susceptibility to C.diff related disorders is also greater for patients who are on prolonged antibiotic treatment for some other disease.

Some of the other known risk factors that can lead to C.diff related disorders are given below.

C.diff related diseases tend to affected older individuals who are over sixty five years of age. All patients who have suffered some form of severe illness requiring prolonged hospitalization are also susceptible. As are patients affected by nasogastric intubation. People who use anti-ulcer medications are also at risk. However, not all medical experts are agreed on this finding and conflicting evidence exists about the use of anti-ulcer drugs and C.diff disorders. The susceptibility of developing C.diff related disease is greatest for patient who stay for long periods of time at the hospital, especially so in long term care facilities.

The actual time period involved in C.diff infection has not been worked out and the time involved from the ingestion of the spores to the appearance of the disease is not known. During a medical study, a series of bacterial cultures taken from hospital patients was analyzed; the evidence indicated that most patients who were suffering from C.diff disease did not have the C.diff infection the previous week. This may point to an incubation time of about a week for the C.diff bacteria, provided other gut bacteria have been largely eliminated from the body through antibiotic use.

This may well suggest that C.diff incubation will be able to take place in less than seven days - within a week's time from initial infection. However, the results from other medical studies point elsewhere, in one study it was found that patients suffered from an increased risk of developing C.diff disease during the first four weeks following discharge from hospital.

Signs and symptoms

C.diff related disorders which are of the mild or benign form usually begin with the patient experiencing mild to moderate diarrhea without any blood in the stool. Some patients have also reported intense cramping sensations in the lower abdominal area as well. However, in all mild forms of the disorder, there are no typical symptoms other than mild tenderness in the abdominal region.

The onset of the severe type of the disorder is marked by strong symptoms. Patients will usually give off profuse and watery diarrhea and complain of excruciating pain in the abdominal area. In addition to this, some patients are also affected by persistent fever, feelings of nausea, and dehydration due to fluid loss in the stool. A bloody stool is rare even in the severe form of the disease, though there may be minute amounts of blood in the stool of some patients.

The appearance of these physical symptoms in the person is usually a signal for full blown colitis, which is a very serious infection of the bowels. The patient does not necessarily get better even if the initial bout of diarrhea completely stops after the severe colitis. The disappearance of the diarrhea may signify paralysis of the bowels, this is a life threatening condition known as toxic mega-colon. Surgery is required to treat the majority of patients affected by toxic mega-colon. This is a complicated dangerous disease and usually out of all patients with C.diff related mega-colon problems that will require surgery, approximately thirty two to fifty per cent will die as a result of complications. Therefore, early treatment and prevention is a priority in dealing with C.diff related illness.

It is advisable for all patients with detectable primary symptoms of C.diff infection to immediately get medical attention and timely treatment. The mild form of C.diff related disease can rapidly progress to the more complicated and severe form of the disease in no time at all.

Patients afflicted by C.diff infections often relapse, and suffer from the infection again. Some debate about this exists among clinicians; the ongoing debate among the medical scientists is whether the relapse of patients with C.diff is really a re-infection with the C.diff from some source or a true relapse due to a hidden pool of the bacterium in the gut.

Relapse rates are quite high, and whatever the exact cause of the relapse, approximately twelve to twenty four per cent of all patients eventually develop a second episode of C.diff disease within about two months from the first occurrence. The relapse rate is also a predictor for future development of the disease, as patients who have already suffered two or more relapses typically have a fifty to sixty five per cent chance of suffering from yet another recurrence of the disease.

Treatment options

The presence of C.diff in the colon of patients is detected by several types of clinical stool tests.

To recover from a mild case of C.diff disease, merely stopping treatment with the antibiotic being used could be enough for some people - this applies to cases, where the use of antibiotics for prolonged period of time led to the population explosion of C.diff bacteria in the gut. In fact, the discontinuation of antibiotic intake was one of the first measures taken by most patients before the arrival of effective treatments for C.diff. Where antibiotic use is a contributory factor for the disease, discontinuation of the antibiotic may be most effective, for example, in one study of twenty C.diff colitis affected patients, all the test patients recovered from the colitis once they stopped the antibiotic treatment.

C.diff infections are almost always treated using a course of antibiotics by most doctors - only specific antibiotics are used in such cases. To treat the mild form of C.diff disease, the antibiotic agent flagyl is the first agent of choice for many doctors, the affected patients normally need to be monitored closely to ensure that the treatment is working as intended. In case of moderate and severe forms of C.diff disease, the antimicrobial agent vancomycin is another good option for such treatments.

That treatment of the C.diff related disease supported by the use of probiotics is confirmed by some clinical evidence based on studies conducted so far in different laboratories. The use of probiotic foods, which are full of friendly bacteria that help in repopulating and replenishing the gut flora may well ensure the effectiveness of the antibiotic treatment, this could help prevents relapse of the C.diff linked disorder. As for the type of probiotic to be used in the treatment, the Saccharomyces boulardii strain of bacteria appears to be particularly effective in most patients, while the use of the Lactobacillus species has also given good results in clinical trails.

Prevention

The disease caused by the C.diff bacterium is easily preventable. Two means of prevention of the C.diff infection are given below.

The first and best method of prevention is proper sanitation, patients and hospital handlers must always wash the hands when inside the hospital or clinic. Spores of the C.diff bacteria which may be transported anywhere can also come into contact with skin, frequent and careful washing of the hands will keep the C.diff spores on the hands from being ingested with food or water.

The second method of prevention of this opportunistic disease is to regulate the use of broad spectrum antibiotics. Indeed, antibiotics must only be used when it becomes absolutely necessary to do so. Viruses are not eliminated by antibiotics and most common respiratory infections are viral in origin, therefore a person should not heedlessly demand the prescription of antibiotics from a doctor every time he or she comes down with a cough or suffers from the common cold. Sparing use of antibiotics ensures that there is no disturbance to the internal intestinal flora, giving C.diff less chance to get a hold.

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Comments

From Tom in Texas - Mar-18-2012
Flagyl is the appropriate first treatment. Vancomycin can result in terrible long term complications, particularly when administered to the young.
From LG - Jan-09-2011
My mother passed away last month from a C.diff infection. She was admitted to the hospital on Tuesday morning and passed away four days later - Saturday morning. She was a fighter and had recovered from two hip surgeries and a six-hour gallbladder surgery over the past few years. I had never heard of C.diff before. She had four strikes against her according to things I have read: 1. she lived in assisted living, 2. she had had major abdominal surgery within a few years (gallbladder), 3. she was taking a PPI antacid for GERD (kills stomach acid that usually kills C.diff) and 4. she had recently been on a broad-spectrum antibiotic that killed all the good flora that usually keeps C.diff in check. I didn't learn about all of these factors stacked against her until it was too late. Hopefully, this information will help others prevent such a tragedy.
From Amie Tims - 2010
My 13 year old son has been in the children's hospital for 7 days now with a severe case of C.diff. I have never heard of this before or knew it could happen from taking 10 days of antibiotics for a skin infection. He was treated first with Flagyl for 4 days and actually was much worse then when we arrived to the hospital. I have read much about C.diff in the last week and have seen several articles that state Vancomycin is now considered the first form of treatment over Flagyl for severe cases. My son has been deathly ill for days for no reason. Why do the GI docs not know this!? I found it quite easily myself online. Severe cases of C.diff should be treated with Vancomycin first. Save yourself or child unnecessary suffering.
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