Pediatric pseudomembranous colitis

　　Pseudomembranous colitis is pathogenic due to toxins produced by two types of flora.
　　1. Clostridium difficile
　　It is an important pathogenic cause of pseudomembranous colitis associated with antibiotics. It was first isolated from the feces of infants by Hall et al. in 1935 as a long, strictly anaerobic, Gram-positive bacillus. This bacterium is a resident bacterium in the body, existing in the intestines of normal people. In patients who have not received antibiotic treatment, the number of Clostridium difficile only accounts for 2% to 3% of anaerobic bacteria, and the toxins produced by the bacteria are few, even not producing toxins that are pathogenic to humans.
　　2. Coagulase-positive hemolytic drug-resistant Staphylococcus aureus
　　After the use of a large amount of broad-spectrum antibiotics (such as terramycin, chloramphenicol, tetracycline, ampicillin, and cefalosporins), various flora in the intestines, including Escherichia coli, are suppressed, and the drug-resistant Staphylococcus aureus proliferates to produce exotoxins, leading to the occurrence of pseudomembranous enteritis. Gram staining of the feces of these patients can reveal clusters of cocci. If the toxins produced by these bacteria are injected into animals, pseudomembranous enteritis can also occur.
　　Under normal circumstances, the gastrointestinal tract is a balanced ecosystem, with a large number of bacteria inside. The species and quantity of these bacteria are basically constant. These bacteria help the bacteria themselves and the antibodies produced in the human body to resist infection. Once certain factors disrupt the ecological balance of this system, it can lead to disease. Antibiotics are most likely to cause a disorder in the proportion of flora, therefore, they are one of the important causes of pseudomembranous enteritis. The antibiotics most commonly associated with pseudomembranous enteritis are ampicillin, clindamycin, and cephalosporins. Those that are not commonly associated are penicillin, erythromycin, and复方新诺明. Those that can occasionally cause it are chloramphenicol, tetracycline, metronidazole, and aminoglycosides. Cancer and surgery are important predisposing factors.

　　Severe cases may develop irreversible shock, rapid dehydration, acidosis; or complications such as acute abdomen with toxic megacolon, colon perforation, or peritonitis, or acute intestinal obstruction. It may also develop hypoproteinemia, polyarticular arthritis, and other complications.

　　1. Asymptomatic infection type

　　Most children are asymptomatic infectious types, but they are important sources of infection.

　　2. Simple diarrhea type

　　Children without systemic symptoms mainly present with loose stools, 3-4 times a day, which are mucous watery stools. Stools may contain white blood cells, and the occult blood test is positive. The sigmoid colonoscopy shows mild edema and congestion of the intestinal mucosa, without pseudomembranes. Symptoms can disappear shortly after discontinuing broad-spectrum antibiotics, and no special treatment is required.

　　3. Pseudomembranous enteritis type

　　Diarrhea is severe, with more than 10 episodes per day, stools resembling egg flower soup, with pseudomembranes and blood in the stool. In addition to diarrhea, children often have systemic symptoms, such as fever, abdominal pain, nausea, anorexia. Abdominal pain usually subsides after diarrhea in severe cases, which may present with dehydration, elevated peripheral white blood cells, a large number of white blood cells in the stool, and the sigmoid colonoscopy shows scattered, plaque-like yellow protuberant pseudomembranes on the mucosa of the affected colon and rectum, with a diameter of 2-10mm, known as pseudomembranous nodules.

　　4. Fulminant colitis type

　　Diarrhea can occur up to 20 times a day, with a large amount, a peculiar smell, often with blood in the stool, pseudomembranes in large or tubular shapes, accompanied by fever, abdominal pain, abdominal distension, and vomiting; in severe cases, there may be high fever, malaise, pale complexion, and even complications such as acute renal failure, shock, DIC, intestinal perforation, and the like. This type has a poor prognosis, and colonoscopy should be avoided in children with this type to prevent intestinal perforation and major surgery.

　　The prognosis of this disease is often quite serious. In clinical practice, it should be possible to prevent the occurrence of the disease as much as possible. First of all, attention should be paid to the use of antibiotics, avoiding the abuse of antibiotics to reduce the incidence of pseudomembranous colitis. The use of broad-spectrum antibiotics should have a clear purpose, and medication should be stopped in a timely manner after achieving the expected efficacy. It is necessary to frequently introduce the disease dynamics of pseudomembranous colitis to medical personnel to prevent the growth of drug-resistant strains. Exogenous Clostridium difficile may be a source of cross-infection in hospitals. Some have detected Clostridium difficile or its spores in the hospital floor, toilet utensils, and the hands and feces of staff caring for patients with pseudomembranous colitis. Therefore, necessary isolation measures and environmental disinfection should be taken for cases of pseudomembranous colitis to prevent cross-infection of Clostridium difficile through rooms, skin, and medical equipment.

　　1. Laboratory examination

　　1. Routine fecal examination:Microscopic examination of fecal smears can be very helpful for clinical judgment if Gram-positive bacilli and their spores are found. Subsequent staged bacterial culture can be performed to check for the presence of a large number of Gram-positive bacteria.

　　2. Bacteriological examination:90% of cases can be cultured Clostridium difficile in the stool at the time of onset. To reduce contact with air during inspection, it is necessary to take at least more fresh stool than the capacity of the container, along with the container, for inspection. The CCFA special medium (composed of cycloserine, thiophenomethoxy cephalosporin, fructose, and protein agar) is inoculated, and Clostridium difficile is selectively isolated under anaerobic conditions. If the colonies are flat, irregularly shaped, rough, and Gram-positive bacilli, a diagnosis can be made.

　　3. Cytotoxicity test:Diluted feces or bacterial culture filtrate has a specific cytopathic effect on tissue culture cells (HELA), which can be neutralized by the antitoxin of Clostridium sordellii, thus confirming that Clostridium difficile is a toxigenic strain.

　　4. Detection of toxin A:Toxicin A can be checked by means of counter-current immunoelectrophoresis, enzyme-linked immunosorbent assay, latex agglutination test, monoclonal antibody method, etc.

　　2. Imaging examination

　　1. Colonoscopy examination:Pseudomembranous colitis can simultaneously affect the colon, especially the sigmoid colon, which can be examined by colonoscopy. There have been reports in China of 16 patients with pseudomembranous colitis who were examined using fiberoptic colonoscopy, among whom 14 had lesions found in the rectum and sigmoid colon. The typical manifestations are erythema and edema of the mucosa, with plaques or fused pseudomembranes on top. Biopsy shows acute inflammation of the mucosa, with necrotic epithelium, fibrin, inflammatory bacteria, and other contents within the pseudomembrane. It is important to grasp the stage of disease progression when using fiberoptic colonoscopy. If the colitis has not yet formed pseudomembranes or if local pseudomembranes have already fallen off, pseudomembranes may not be found under the microscope. Therefore, pseudomembranes should not be the sole diagnostic criterion. The absence of pseudomembranes does not necessarily exclude the disease. The lesions of pseudomembranous colitis can be distributed in a jumping pattern. To prevent the omission of small lesions, the scope of endoscopy must include the entire colon, and representative lesions should be taken for biopsy, with a certain depth of sampling.

　　2. Abdominal X-ray film:There is often thickening of the intestinal mucosa, intestinal distension, and some intestinal paralysis patients may present with intestinal obstruction. Barium enema may reveal brush-like edges of the intestinal lumen, finger pressure signs, and scattered circular or irregularly shaped filling defects. Double-contrast barium enema can provide more diagnostic indicators, but it must be operated with caution to prevent the occurrence of intestinal perforation.

　　3. Ultrasound diagnosis:Ultrasound can detect local intestinal wall pseudomembrane, severe thickening caused by mucosal and submucosal edema, narrowing or disappearance of the intestinal lumen. A careful examination may reveal pseudorenal signs resembling intestinal tuberculosis or tumor in the lower right abdomen. Good-quality ultrasound diagnostic equipment can also more accurately differentiate the layers related to the lesions. In addition, ultrasound diagnosis can detect ascites and other complications associated with the disease.

　　4. CT diagnosis:The CT findings are not specific, and occasionally, thickened intestinal walls with low attenuation may be found.

　　Dietary suggestions for children with pseudomembranous colitis include the following: 1. Focus on light and plain foods, pay attention to dietary regularity. Eat more fruits and less greasy food. 2. Follow a reasonable diet based on the doctor's advice.

　　First, treatment

　　1. Discontinuation of antibiotics: Once the diagnosis is confirmed, the use of the original antibiotic should be discontinued immediately, with the most common being ampicillin (aminobenzoic penicillin), penicillin, cephalosporins, lincomycin (clindamycin), and others. For mild cases, symptoms improve significantly within 48 hours after discontinuation, and are cured within 7 to 10 days. Severe cases may take longer.

　　2. For children with simple diarrhea, no special treatment is required, or the use of intestinal microecological regulation drugs, such as bifidobacteria and lactobacillus preparations, can be used to promote the growth of normal flora in the intestines, thereby controlling clinical symptoms. For those who cannot take oral medication, administration through a gastric tube or enema can also achieve the therapeutic purpose. Children with severe diarrhea should pay attention to the balance of water and electrolytes, and timely fluid replacement therapy should be provided when necessary.

　　3. Antibiotic treatment is generally changed to other antibiotics when the condition is severe or when there is no improvement after 48 hours of discontinuing the previously used antibiotics. It is advisable to use antibiotics that are not easily absorbed in the intestines and do not easily induce Clostridium difficile enteritis. A large dose and a long course of treatment are required to achieve the purpose of clearing pathogenic bacteria and preventing recurrence. Appropriate oral or intravenous administration of antibiotics is recommended against pathogenic bacteria. During treatment, anti-peristalsis drugs should be avoided as they can increase the retention and absorption of bacteria and toxins in the intestines, and can also induce toxic megacolon.

　　(1) Vancomycin: Vancomycin has an efficacy of up to 100% in treating Clostridium difficile, with a dosage of 40mg/kg, taken in three divided doses, for a course of 7 to 10 days. Generally, symptoms disappear within 2 to 4 days after the start of treatment.

　　(2) Metronidazole (metronidazole): 20mg/kg per day, taken three times a day, for a course of 7-10 days, and vancomycin can also be selected at the same time.

　　(3) Rifampin: 10-15mg/kg per day, taken three times a day, for a course of 1-2 weeks. In critically ill children with toxic megacolon, intestinal perforation, and inability to take oral medication, the above drugs can be administered alternately by intravenous infusion, but when any drug is administered alone by intravenous infusion, it cannot achieve a concentration in the colon sufficient to clear the pathogen. Once the condition improves, oral medication should be resumed immediately.

　　(4) Treatment during recurrence: In cases with mild recurrence of Clostridium difficile infection, drug treatment may not be required. In cases with severe recurrence, metronidazole or vancomycin should be continued, but the course of treatment should be extended to 14 days.

　　(5) Oral colestyramine (cholestyramine): Oral colestyramine (cholestyramine) exerts an ionic exchange effect in the intestine, which can adsorb the toxins produced by Clostridium difficile in the intestinal lumen and excrete them. Children can take colestyramine (cholestyramine) twice a day at the same time as vancomycin. However, it can also adsorb vancomycin, so these two drugs should be taken separately, 3 hours apart. Oral drugs to promote the recovery of intestinal flora can also be taken, such as oral bifidobacterium triple viable preparation (Peifengkang), bifidobacterium (Lizhuchang) and other viable preparations.

　　4. Other treatments include correcting dehydration and acidosis, blood transfusion, human serum albumin, and adrenal cortical hormones. Milk obtained from immunized cows with Clostridium difficile can also be used to neutralize toxins in the intestinal lumen. Treatment with antiserum against Clostridium difficile is also effective. Intravenous injection of immunoglobulin can be tried for refractory Clostridium difficile enteritis to neutralize bacterial toxins in the child's blood.

　　5. In case of complications and intestinal perforation, timely transfer to surgical treatment is required. In cases with renal failure, shock, and DIC, timely emergency treatment should be provided.

　　Second, Prognosis

　　Immediately stop using the original antibiotics. In mild cases, the symptoms improve significantly after 48 hours of drug discontinuation. This disease can be cured in 80% to 90% of cases with 1 to 2 weeks of regular treatment. Severe cases may take longer. A few cases may relapse 1 to 2 weeks after drug discontinuation, or the course of the disease may last for 1 to 4 months. Re-selecting the above drugs for treatment can still achieve the goal of cure. However, delayed treatment and fulminant prognosis are poor.