Clostridium difficile infection (CDI) is a gastrointestinal condition caused by toxin-producing strains of C. difficile bacteria. Commonly referred to as C. diff infection, this illness is a result of an excess of the Clostridioides difficile bacterium (also referred to as C. difficile or C. diff for short) causing an infection of the colon (large intestine).

Known as one of several healthcare associated infections that continue to impact public health, C. difficile bacteria forms spores that are very difficult to eliminate from the hospital environment, leading to infection of hospitalized patients. When in spore form, C. difficile bacteria have a protective coating that allows them to live on surfaces for months (or even years). Once ingested, they become active again.

While these infections are most common in hospitals or health care facilities, C. difficile spores are found in abundance in the environment, so exposure to this resilient, spore-forming pathogen can be presumed to be both continuous and unavoidable. There are ways to reduce the presence of C. difficile spores, which we will discuss in an upcoming article.

Common Clostridioides difficile Infection Symptoms

C. difficile bacteria affects people in different ways, and infection can lead to a variety of health issues. Some individuals carry C. difficile bacterium and don’t have any symptoms whatsoever—though they may spread it to others who may become ill.

Under normal circumstances, healthy bacteria in the gut keep C. difficile growth in check. Disruption of gut microbiota due to exposure to broad spectrum antibiotics or chemotherapy predisposes the patient to CDI.

It is important to know that the symptoms outlined below can be caused by any number of illnesses and infections, which is why it is important to visit a health care provider for an accurate diagnosis and prompt treatment.

Mild & Moderate Infection Symptoms

For some who suffer from a C. difficile colitis infection, the symptoms will be mild or moderate, especially with prompt treatment.

Cramping—Mild cramping in the abdominal area, accompanied by mild tenderness that can last for multiple days.

Diarrhea—Even in less severe cases of CDI, watery diarrhea multiple times a day over a course of several days is not uncommon.

Nausea—Nausea is one of the most common and debilitating symptoms of mild to moderate Clostridium difficile infections. From dizziness to lack of appetite and excess sweating, nausea can cause a variety of symptoms that should be addressed as soon as possible.

Severe Infection Symptoms

In some cases, Clostridioides difficile infection symptoms may go away on their own as the body fights off the infection. However, without treatment, the symptoms can worsen—sometimes rapidly. Severe infections can quickly lead to life-threatening conditions and can require hospitalization in some instances.

In severe cases, C. difficile can cause symptoms such as:

Abdominal Pain—Persistent or frequent abdominal pain is another symptom to watch for. Pain may be severe enough to disrupt daily activities and can lead to issues with eating and drinking. This pain can also be an indicator of a swollen abdomen

Swollen Abdomen—A tender or painful stomach area can be a symptom of a swollen colon. In some rare cases, C. difficile colitis can lead to an enlarged colon, inflammatory bowel disease, and toxic megacolon. If not treated quickly, toxic megacolon can lead to blood loss, sepsis, colon perforation, shock, and death.

Fever—High fevers are possible as the body attempts to fight off the infection caused by excess numbers of C. difficile bacterium. This can lead to overheating and excess sweating, along with a range of other negative side effects, including tiredness, difficulty concentrating, headaches, body aches, and chills.

Frequent Watery Diarrhea—In more severe cases of infection, a person may experience severe diarrhea over 10 times per day. The diarrhea is generally very watery, and in some cases may contain blood.

Severe Nausea—As nausea worsens, it can lead to other symptoms outlined in this list—including vomiting, queasiness, excess sweating, dehydration, lack of appetite, and more.

Rapid Heart Rate & Palpitations—While a rapid heart rate or heart palpitations on their own can be caused by a variety of stressors (exercise, medication, or stress), issues with rapid or irregular heartbeat can be a symptom of severe CDI. If you notice abnormal heart rhythms or an elevated pulse, it is important to visit your healthcare provider quickly.

Dehydration—Due to increased frequency of diarrhea, those suffering from an infection may become dehydrated, which can be life-threatening when not treated quickly. Other symptoms can contribute to dehydration as well, such as nausea, vomiting, fever, and excess sweating.

Weight Loss—Some patients suffering from CDI may experience weight loss due to a variety of symptoms, including loss of appetite (often associated with nausea), vomiting, and diarrhea. This weight loss can negatively impact overall health, so quickly treating the symptoms causing it is essential.

Blood in the Stool—Bloody stool can be caused by bleeding anywhere along the digestive tract, and it appears in a variety of different ways. In some cases, stool may be very dark (melena), or bright red (hematochezia). In some instances, the blood may not be visible to the eye (fecal occult blood).

Pus in the Stool—Whiteish or yellowish coloring in stool is very likely pus, especially when accompanied by other symptoms of illness. Pus in the stool is a very strong indicator of an infection—C. difficile-related or otherwise. Be sure to seek medical attention as soon as you notice potential pus to diagnose the cause and begin treatment, as severe infections are unlikely to be resolved without medical aid from a health professional.

Kidney Failure—Severe CDI can lead to kidney failure, which is a life-threatening condition that requires intensive treatment. Symptoms of kidney failure include a range of the other symptoms listed, including nausea, irregular heartbeat, fatigue, confusion, dizziness, and headaches. Other signs of kidney failure include a decrease in urination frequency and output, which may lead to swelling of the feet, ankles, or legs due to fluid retention.

When to Consult a Healthcare Provider

If you are experiencing any of these symptoms, it is important to speak with a health care professional right away to receive a proper diagnosis and treatment. Even if the underlying cause is not C. difficile, it is important to determine the cause of your condition so that proper treatment may be administered.

When—and if—the source of your ailment is confirmed to be a C. difficile infection, there are two approved antibiotic treatments healthcare providers may administer: vancomycin and fidaxomicin. While both treatments are fairly effective, they are not 100% reliable, and recurrence is a possibility.

Recurrent C. difficile Infection

C. difficile colitis may occur more than once, even after treatment. When this happens, it is referred to as recurrent C. difficile. When C. difficile infection recurs, similar symptoms to previous infections can manifest, often requiring additional antibiotic treatment and re-hospitalization.

This is part of the issue with existing C. difficile treatment options: recurrence rates range from 15-30% and result from reinfection by C. difficile spores.

Recurrence rates in CDI patients treated with vancomycin exceed 20%. Recurrence following fidaxomicin treatment is somewhat lower, with the notable exception of those infected with the recently emerging epidemic strains (BI/NAP1). Those patients suffer recurrence rates above 20% with either vancomycin or fidaxomicin treatment.

In addition, these antibiotics may cause disruption of normal intestinal microbiota. Due to the resilience of C. difficlie spores, CDI will likely continue to spread as an infectious disease (especially in healthcare settings) with little hope of effective disease control for the foreseeable future. With this in mind, developing more optimal and effective therapies is crucial for overall public health and wellbeing.

Preventing Recurrent C. difficile Infection

The team at Crestone, Inc. is heavily focused on finding a better solution to treat C. difficile infection. CRS3123 is a small molecule protein synthesis inhibitor that targets Clostridioides difficile by acting on the target methionyl-tRNA synthetase (MetRS).

CRS3123 offers a variety of potential advantages compared to currently available CDI therapies. CRS3123 is highly potent against all clinical isolates of C. difficile, and it utilizes a novel mechanism of action so that it does not compromise the utility of systemic antibiotics (such as vancomycin). Click here to learn more about CRS3123. If you suffer from recurring C. difficile infection, you may be a candidate for our ongoing clinical study, 19-0021, which you can learn more about here.