Introduction
A global clinical concern today is the rising frequency of drug-resistant, recurrent, or non-hospital Clostridioides difficile infection, as well as the occurrence of severe and complex Clostridioides difficile infection. Compared to the general population, individuals with chronic kidney disease (CKD) had higher rates of Clostridioides difficile infection. CKD patients' immune system deficiencies, dysbiosis, and repeated use of antibiotic therapy appear to be linked to Clostridioides difficile infection. One prevalent disease seen in CKD patients is dysbiosis. It could be linked to low dietary fiber, less fluid intake, frequent physical activity, constipation, poor gastrointestinal motility, multidrug medication, and the uremic milieu in stage 5 chronic kidney disease. The clinical presentation of Clostridioides difficile infection in CKD patients is similar to that of the general population; however, reports indicate a higher frequency of severe CDI and recurrence of Clostridioides difficile infection.
What Is Clostridium Difficile?
Clostridium difficile is a gram-positive, anaerobic bacteria that can form spores. It was moved from the genus Clostridium to the genus Clostridioides in 2016 after a genetic study. The use of antibacterial medications is linked to diarrhea caused by Clostridium difficile. Although Clostridium difficile infection (CDI) was previously thought to be exclusively a nosocomial illness, in recent years, it has also been found to cause diarrhea in an increasing number of individuals who are not hospitalized.
The majority of these infections happen in:
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Individuals 65 years of age and older who receive medical care and antibiotics.
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Long-term residents of hospitals and assisted living facilities.
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Those with compromised immune systems or those who have already contracted Clostridioides difficile infection.
What Are the Symptoms of Clostridium Difficile?
Following the initiation of antibiotic treatment, symptoms may appear a few days or several weeks later. Some symptoms are:
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Diarrhea is defined as having loose, watery feces for a few days.
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Chills.
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Stomachache.
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Decrease in hunger.
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Sick feeling.
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C. diff is easily contagious among individuals.
What Is the Pathogenesis of Clostridioides Difficile Infection in CKD Patients?
The spores that cause CDI are resistant to high temperatures, acids, and antibacterial medications. The disease is transferred through the fecal-oral pathway. Spores in the duodenal lumen become vegetative forms of bacteria when they touch bile acids upon ingestion. The vegetative form of Clostridium difficile may colonize the large intestine in favorable circumstances, such as antibiotic-induced dysbiosis.
During the process known as "sporulation," Clostridium difficile converts the vegetative forms of the bacteria into spores in the large intestine while also producing enterotoxins. The primary pathogenic characteristic of Clostridium difficile is the synthesis of bacterial toxins A and B, which deactivate Rho GTPase, causing actin fiber depolymerization and colon epithelial cell destruction.
These toxins also increase the generation of oxygen free radicals, pro-inflammatory interleukins (primarily IL-1β and IL-18), and tumor necrosis factor-alpha (TNFα) in the intestinal lumen. In addition, it promotes the recruitment of macrophages and neutrophils, opens epithelial junctions, raises vascular permeability, and triggers epithelial cell death. The intestinal mucosa can be damaged, leading to an overabundance of mucus and diarrhea, colitis, and the development of pseudo-membranes made of fibrous exudates, inflammatory cells, and necrosis.
What Are the Risk Factors for Clostridioides Difficile Infection in Patients With CKD?
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Antibacterial agent exposure is the most significant risk factor for Clostridium difficile infection, particularly for drugs with a broad spectrum of antibacterial activity (Penicillin, cephalosporins, fluoroquinolones, and Clindamycin).
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In patients with chronic kidney disease (CKD), these medications, particularly cephalosporins, Penicillin, and fluoroquinolones are frequently used (and others) in urinary tract infection therapy.
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A few other risk factors for CDI include advanced age, recent hospitalization, concomitant conditions (particularly cancer), CKD, liver cirrhosis (it is a disorder that causes the liver to become permanently damaged and scarred), diabetes, inflammatory bowel disease (it is an idiopathic illness brought on by a dysregulated immunological response to the host's gut microbiota), immune system disorders (HIV-positive patients, patients undergoing solid organ transplantation or hematopoietic stem cell therapy).
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Post-gastrointestinal surgery, endoscopy, and medications that prevent the stomach from producing acid, such as type 2 histamine receptor antagonists or proton pump inhibitors.
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The primary risk factors for CDI in patients with chronic kidney disease (CKD) are recurrent infections, the use of broad-spectrum antibiotics, higher hospitalization rates than in the general population, hypoalbuminemia (the blood's albumin content is low), and compromised immune system performance.
How to Diagnose Clostridioides Difficile Infection?
To diagnose CDI, a patient must have either megacolon toxic or diarrhea, along with one of the following criteria: have toxins A or B in the stool sample; have a strain of Clostridium difficile that produces toxins in the stool culture; have pseudomembranous enteritis (it is a severe case of the large intestine's inner lining inflammation) identified during endoscopy or surgery; or have pseudomembranous enteritis confirmed by histopathology.
Stool samples from patients suspected of CDI are used as laboratory test material. Rectal swabs should be collected for molecular testing or cultured to identify the existence of the toxin-causing strain of Clostridioides difficile in the absence of diarrhea in the intestinal blockage. Within two hours of collection, the material needed for testing must be delivered to the lab.
Many tests with varying sensitivity, specificity, and methodologies are utilized to diagnose Clostridioides difficile infection. Enzyme immunoassays that detect toxins A and B have a low sensitivity and a moderate specificity. Nucleic acid amplification testing (NAAT), the enzyme-linked immunosorbent assay glutamate dehydrogenase (EIA GDH), and toxigenic culture (TC) testing are high-sensitivity and low to intermediate specificity procedures.
Genes encoding Clostridium difficile toxins are found using NAAT molecular assays. A multi-step diagnostic algorithm is currently advised. First, a high-sensitivity test such as the NAAT or EIA GDH should be conducted. In the event of a positive result, enzyme immunoassays are carried out to identify toxins A and B in the second step.
What Is the Treatment for Clostridioides Difficile Infection in Patients With CKD?
Oral administration of Vancomycin and Fidaxomicin is the primary treatment for CDI. Patients with CKD receive the same CDI treatment as the general public. There are various recommended algorithm types based on the severity and existence of recurrence of CDI. Vancomycin (125 milligrams orally four times a day for ten days) or Fidaxomycin (200 milligrams orally twice daily for ten days) is advised for the first mild or severe episode. If neither of the two medications listed above is available, Metronidazole 500 milligrams orally three times a day for ten days is permissible.
For severe CDI, Metronidazole is not advised as a substitute therapy. Vancomycin 500 milligrams four times a day, orally or enterally (via a nasogastric tube), is recommended in the event of a fulminant initial episode of CDI (CDI accompanied by hypotension or shock, intestinal blockage, or toxic megacolon). Rectal enemas are used to give Vancomycin in cases of intestinal blockage. Furthermore, Metronidazole should be administered intravenously at 500 milligrams every 8 hours. The course of treatment for the initial episode of CDI determines the course of treatment for the first recurrence. It is advised to administer Vancomycin at a dose of 125 milligrams orally four times a day for ten days if Metronidazole has been taken previously. For recurrent CDI, extended therapy with lowering and pulsing oral Vancomycin dosages should be initiated if Vancomycin or Fidaxomicin were utilized. 125 mg four times a day is the recommended dosage, and such therapy lasts ten to fourteen days. After that, it is to be taken twice a day, once a day, and then every two or three days for the remaining eight weeks. An alternative to Vancomycin therapy could be taking 200 mg of Fidaxomicin orally twice daily for ten days.
Conclusion
There is a two-way interaction between the gastrointestinal (GI) tract and the kidneys. GI symptoms, such as dysgeusia, anorexia, dyspepsia, hiccups, nausea, and vomiting, are frequently experienced by patients with chronic kidney disease (CKD). Patients with chronic kidney disease have a higher risk of CDI. Constipation and diarrhea are two lower gastrointestinal symptoms that CKD patients experience. Individuals with CKD follow the normal population's CDI treatment plan. There is no need to change the dosage of Vancomycin and Fidaxomicin in individuals with renal insufficiency because these medications are not absorbed in the gastrointestinal system when administered to treat CDI.
