What is Clostridioides difficile infection (C. diff)?
Clostridioides difficile, or C. difficile for short, is a type of bacteria that forms spores and is known for causing infections. It’s the main reason people get diarrhea after taking antibiotics. The symptoms of a C. difficile infection can range from none at all to diarrhea, and it can even progress to more serious conditions. Cases of this infection are found both in healthcare facilities and in the community.
A new, more harmful strain of this bacteria, known as NAP1, has been causing more and more infections over the past twenty years.
Healthy people can carry C. difficile without getting sick, and the bacteria can survive on surfaces in hospitals and in the soil for a long time. If hospitals and medical equipment aren’t cleaned properly, these can become breeding grounds for the bacteria.
The biggest risk for getting a C. difficile infection is from taking antibiotics, especially broad-spectrum antibiotics. These can disrupt the natural balance of bacteria in your gut and let the C. difficile bacteria grow and cause an infection. Other things that can increase your risk include getting older, having a weakened immune system, other health conditions, using proton pump inhibitors, recent stays in healthcare facilities, not getting appropriate care for infections, and not using antibiotics wisely.
We’ve started to see more and more cases of C. difficile infections in people who haven’t spent a lot of time in healthcare facilities, including younger and healthier individuals. New techniques have shown us that these bacteria can also come from the environment, food, soil, and animals.
Managing these infections is difficult because they’re becoming more common, they’re appearing in a wider range of places, they can keep coming back, and they are causing more and more health problems. It’s crucial to understand how these infections spread so we can take effective measures to prevent and control them. This includes smart use of antibiotics, good hand hygiene, keeping environments clean, and quickly identifying and managing cases.
What Causes Clostridioides difficile infection (C. diff)?
Clostridioides difficile, often referred to as C. difficile, is a bacteria that can cause inflammation in the colon, known as colitis. This bacteria can be found in healthcare facilities across the world, making it one of the most common causes of infections picked up in hospitals. The severity of symptoms can range greatly, from no symptoms at all, to mild diarrhoea, to potentially life-threatening conditions.
The most common cause of a C. difficile infection is the use of antibiotics, especially those that are broad-spectrum. These include penicillins, cephalosporins, fluoroquinolones, and clindamycin. We’re learning more about the role of the gut microbiome – the trillions of microbes that live in our intestines – in diseases, which is helping us better understand this infection.
When someone carries C. difficile without symptoms and takes antibiotics, the balance of the microbiome can be disturbed, allowing the bacteria to grow and cause an infection. Other risk factors can include the use of drugs that reduce stomach acid, old age, a weakened immune system, other underlying health conditions, previous C. difficile infections, kidney and liver failure, and longer stays in hospital.
C. difficile produces two toxins – toxins A and B – which can cause disease. Most harmful strains of C. difficile produce both toxins, but there are reports of strains that only produce one of the toxins. Over time, new strains of C. difficile have emerged that are more harmful, more resistant to antibiotics, and cause more severe disease. One such strain is known as NAP1/B1/027, which produces increased quantities of toxins A and B, in addition to another toxin called binary toxin CDT, and is resistant to a group of antibiotics known as fluoroquinolones.
Risk Factors and Frequency for Clostridioides difficile infection (C. diff)
C difficile is a major health concern as it’s often the cause of colitis following antibiotic use in healthcare settings. It’s easily transmittable and is associated with considerable sickness and death. The bacteria is found everywhere, and up to 3% to 5% of healthy people without infection carry it in their intestines. Although it mainly spreads through fecal-oral transmission, it can also come from other environmental sources such as soil. However, transmission is most common via contaminated surfaces in hospitals, often as spores.
Certain surfaces and medical equipment in healthcare facilities can house C difficile spores. If good infection prevention and control practices, including proper cleaning, aren’t enforced, these spores can be passed to patients. This is why healthcare environments are commonly associated with C difficile transmission: it’s tough to completely wipe out spores and antimicrobial use is common, which allows C difficile infections to flourish.
Although C difficile infections are primarily linked with healthcare environments, recent data show a rise in infections in the community involving people not affiliated with a healthcare system or exposed to antibiotics. This presents a need to boost detection, surveillance, and infection prevention and control practices. Misuse of antibiotics is a big problem, greatly increasing the risk of C difficile infections. During hospital stays, over half of patients receive antibiotics, with 30% to 50% of those prescriptions being unnecessary or incorrect.
In the last 20 years, efforts globally have improved the ability to detect and monitor C difficile infections, and estimate the impact they have. Countries are working hard to enact protocols and tools for detection, surveillance, and infection prevention, especially in hospitals. But, it’s important to note that practices vary and resources differ, which can influence data accuracy regarding C difficile’s impact.
The early 2000s saw a big increase in C difficile infections and related hospital stays, due to a new strain of the bacteria. It became the main cause of gastroenteritis, leading to a big jump in death rates. Estimates suggest that C difficile infections added an extra $4.8 billion in costs to US acute-care facilities.
An article in 2011 highlighted a rise in C difficile infection rates in 10 regions across the US compared to the previous 10 years, particularly among women and those aged 65 and above. These increases could be due to more sensitive testing methods. About 500,000 Americans get a C difficile infection every year. Of those, roughly 29,000 die within a month of diagnosis, with 15,000 of those deaths directly tied to the infection. About 83,000 patients experience a recurrence, with 29,000 of them dying within 30 days of the first diagnosis.
More recent data from the US and Europe show a decline in C difficile infections in healthcare settings, particularly the newer strain of the bacteria. This could be due to a combination of factors: reducing unnecessary antibiotic use, implementing antibiotic stewardship practices, and improving infection control procedures. However, there’s still a lot of variation globally and between countries in testing, infection prevention, and control practices.
Signs and Symptoms of Clostridioides difficile infection (C. diff)
C difficile infections can show up in different ways. Some people don’t show any symptoms, while others can have mild to severe symptoms. These can fluctuate based on their general health and the specific strain of C difficile causing the issue. Symptoms associated with diarrhea and colitis caused by C difficile can be:
- Watery diarrhea with mucus or blood
- Loss of appetite (anorexia)
- Nausea
- Vomiting
- Mild fever
- Lower abdominal pain
In severe cases, the patient can develop fulminant colitis, which is a very severe form of inflammation in the colon. The symptoms of this include:
- Diarrhea
- Spread-out abdominal pain
- Bloating (abdominal distension)
- Dehydration (hypovolemia)
- Extreme expansion of the colon (toxic megacolon)
- Tear in the wall of the bowel causing infection in the abdomen (perforated bowel with peritonitis)
Other issues that can occur due to the disease include loss of protein through the intestines and symptoms that affect areas outside the colon (extra-colonic symptoms), such as appendicitis and reactive arthritis. Repeated infections caused by C difficile are known as ‘recurrent infections’. Even after successful treatment and symptom resolution, the infection can come back. Situations that increase the risk of recurrence include recent hospitalization, antibiotic use, or close contact with people who have experienced diarrhea.
Testing for Clostridioides difficile infection (C. diff)
If you experience three or more incidents of loose stool within 24 hours, especially if you’ve been hospitalized or used antibiotics over the past three months, it’s essential to consider the possibility of a C. difficile infection. It’s also crucial to suspect this infection if diarrhea continues 48 hours after being admitted to the hospital. Even those who don’t have previous exposure should be evaluated for potential community-acquired cases.
There are various tests that can diagnose a C. difficile infection, including enzyme immunoassays for glutamate dehydrogenase, producing cultures that are toxic, cell culture cytotoxicity neutralization tests, toxins A and B enzyme immunoassays, and nucleic acid amplification tests (NAATs). Because a single test might not provide enough information, a two-step sequential testing approach is typically used. The primary goal is to detect the presence of the C. difficile antigen, either by testing for glutamate dehydrogenase produced by C. difficile or through NAATs. If these initial tests are negative, the testing is usually ended. However, if positive, they don’t automatically mean toxins are present, so additional tests are needed to confirm the production of the toxin.
Most protocols recommend a two-step method to diagnose C. difficile infections, though using a NAAT alone or along with glutamate dehydrogenase in a two-step process is also acceptable. While anaerobic culture is an option, it can be time-consuming. Research has shown that diagnostic approaches using polymerase chain reaction (PCR), whether a single or multistep process, provide the highest accuracy for diagnosing C. difficile. In certain situations, additional diagnostic tools like abdominal and pelvic imaging or lower gastrointestinal endoscopy could be necessary, especially in severe instances of colitis or when considering other potential diagnoses.
Treatment Options for Clostridioides difficile infection (C. diff)
Treating C. difficile infections requires multiple steps, such as putting into place protocols to prevent and control infection, making a definite diagnosis, stopping unnecessary antibiotics if possible, and giving appropriate medication according to established guidelines. If a patient doesn’t have symptoms like diarrhea, there’s no need to test for C. difficile infection. If a patient tests positive but doesn’t have symptoms, treatment isn’t necessary.
Successful treatment is characterized by the end of diarrhea or the formation of solid stool at least two days after the treatment has been completed. A failure to respond to treatment after a certain time period is known as refractory C. difficile infection. Recurrence is defined as a new episode within eight weeks after the complete resolution of a previous C. difficile infection.
Severe C. difficile infection is typically marked by a high white blood cell count (more than 15,000 cells/μL), low serum albumin (below 3 g/dL), and an elevated serum creatinine level (more than 1.5 times the patient’s normal level).
Many professionals rely on different treatment guidelines for C. difficile infections. The primary treatment approach is generally consistent across most guidelines, which includes use of oral vancomycin, oral fidaxomicin, and intravenous metronidazole. Oral vancomycin and fidaxomicin are currently standard treatment options. Metronidazole should only be considered if vancomycin or fidaxomicin are unavailable or if the patient has a condition called ileus.
Bezlotoxumab, a new drug that targets C. difficile toxin, has shown promise in managing recurrent infections. Fecal transplantation, which involves introducing fecal matter from a healthy donor into a patient’s gastrointestinal tract, has reported an 80% to 90% success rate in reducing C. difficile recurrence.
For initial treatment of C. difficile infections, fidaxomicin and vancomycin are the first choices, with specific recommendations for first episodes, recurrences, or severe infections. In cases where fidaxomicin is unavailable, vancomycin should be given. Similarly, if neither is available, metronidazole should be given orally.
For severe initial incidents of C. difficile infection characterized by signs of shock or ileus, treatments include oral fidaxomicin or vancomycin, possibly supplemented by metronidazole given intravenously. In some severe cases, a surgical procedure may be necessary.
What else can Clostridioides difficile infection (C. diff) be?
If you have symptoms that seem like a C. difficile infection, your doctor may consider other conditions, illnesses, or infections that could lead to similar symptoms. These include:
- Crohn’s disease, a type of inflammatory bowel disease
- Diverticulitis, an inflammation or infection of small pouches in your digestive tract
- Irritable bowel syndrome, a common disorder that affects the large intestine
- Malabsorption, a faulty process where your body isn’t properly absorbing nutrients from your diet
- Peritonitis, an inflammation of the thin layer of tissue that lines the inside of your abdomen
- Salmonella infections, a bacterial infection that can cause diarrhea, fever, and stomach cramps
- Shigellosis, a bacterial infection that can cause severe diarrhea
- Ulcerative colitis, a type of inflammatory bowel disease that causes inflammation and ulcers in your digestive tract
- Vibrio infections, a type of bacterial infection often acquired by consuming undercooked seafood
- Viral gastroenteritis, often referred to as stomach flu
Your doctor would need to perform specific tests to accurately diagnose which condition is causing your symptoms.
What to expect with Clostridioides difficile infection (C. diff)
C difficile infections pose a considerable challenge to healthcare systems. These infections result in longer hospital stays, increased healthcare costs, higher sickness and death rates, recurring episodes of the disease, and an increase in disability-adjusted life years (DALYs). DALYs are a measure of overall disease burden and estimate the years a person lives with disabilities after getting sick and the years of life lost due to early death, compared to a standard life expectancy.
Possible Complications When Diagnosed with Clostridioides difficile infection (C. diff)
The infection caused by the bacteria called C difficile is a major health issue among hospitalized patients. It is serious because it can lead to harmful conditions like toxic megacolon, colonic perforation, and sepsis. These conditions can significantly increase the person’s likelihood of death and could extend their hospital stay. Not only that, but once a person has had this type of infection, it is also more likely to recur.
In severe cases, known as fulminant colitis, surgical treatment may be needed. This might involve removing most of the colon but keeping the rectum, a procedure known as subtotal colectomy with rectal preservation. However, this too comes with its own risks, including the potential for complications like toxic megacolon, intestinal perforation, and necrotizing colitis, where parts of the colon die.
Possible complications include:
- Toxic megacolon
- Colonic perforation
- Sepsis
- Increased chance of death
- Extended hospitalization
- Increased chance of getting the infection again
- Potential complications from surgery, such as:
- Toxic megacolon
- Intestinal perforation
- Necrotizing colitis
Preventing Clostridioides difficile infection (C. diff)
Patients need to be fully informed about dealing with C difficile infection. This includes learning about its typical progression and treatment, its chance of recurring, how to use antibiotics responsibly, and steps to prevent it from spreading within the home. It is essential for patients to stick to the recommended duration of the treatment and avoid other antibiotics while being treated for C difficile infection.
Patients should know that their symptoms should gradually fade and that they should contact their doctor promptly if symptoms persist, get worse, or come back. This could signal a recurrence or increase in severity of the original infection.
Moreover, patients should be told to wash their hands thoroughly with soap and water. This is particularly important after using the restroom since antibacterial hand gels may not eliminate C difficile spores. Regularly washing hands can help prevent the spread of C difficile within the home.