OVERVIEW
Pseudomembranous enteritis is an acute inflammatory disease of the intestinal tract, mostly occurring in middle-aged people aged 50 to 60 years, with more women than men. Pseudomembranous enteritis is named after a layer of pseudomembrane on the surface of necrotic mucosa in the small intestine or colon, and it tends to occur after major surgery and application of broad-spectrum antibiotics, so it is also called post-surgical enteritis and antibiotic enteritis. The essence of pseudomembranous enteritis is that the ecological balance of intestinal flora is imbalanced, and the intestinal flora plays a non-specific immune role through the following mechanisms: ① H2O2 effect; ② bacterial toxin effect; ③ occupancy protection; ④ organic acid effect; ⑤ competition for nutrients. It can be seen in shock, heart failure, uremia, colonic obstruction, diabetes mellitus, leukemia, aplastic anemia, and cardiopulmonary chronic diseases.
Causes
Pseudomembranous enteritis is caused by two flora producing toxins.
1. Clostridium difficile
Clostridium difficile is an important cause of antibiotic-associated pseudomembranous enteritis. It is an elongated, strictly anaerobic, gram-positive bacillus that was first isolated from the feces of infants by Hall et al. in 1935. This bacterium is a resident bacterium in the body present in the normal human gut. In patients not treated with antibiotics, C. difficile numbers only 2% to 3% of anaerobic bacteria, and the bacteria produce few, if any, toxins that are pathogenic to humans. The detection rate of Clostridium difficile in the population is 5% to 13%, and under normal circumstances these bacteria restrain each other from proliferating and causing morbidity. Long-term use of large amounts of antibiotics, can inhibit the growth of various types of bacteria in the intestine, not affected by antibiotics, drug-resistant Clostridium difficile is rapidly multiplying, Clostridium difficile in the stool can be as high as 10% to 20% of the anaerobic bacteria, producing a large number of exotoxins, causing mucosal necrosis, oozing inflammation with the formation of pseudomembranes, in all the pseudomembranous enterocolitis in the stool can be found in almost all of this exotoxin.
2. Coagulase-positive hemolytic drug-resistant Staphylococcus aureus
When the use of a large number of broad-spectrum antibiotics (e.g., oxytetracycline, chloramphenicol, tetracycline, ampicillin, vancomycin, etc.) inhibits the intestinal flora, including Escherichia coli, drug-resistant Staphylococcus aureus reproduces in large numbers to produce exotoxin, resulting in the development of pseudomembranous enterocolitis. Gram staining of the fecal smears of such patients can reveal heaps of cocci, and pseudomembranous enteritis can also occur if the toxin produced by this bacteria is injected into animals.
Symptoms
The disease usually occurs in the course of tumors, chronic wasting disease, and the application of antibiotics after major surgery, and most have an acute onset and rapid progression of the disease. The earliest onset of the disease can be a few hours after the start of the drug, but it can also be about 3 weeks after the discontinuation of the drug, and about 20% of patients start the disease within 2 to 10 days after the discontinuation of antibiotics.
1. Fever
10% to 20% of patients have fever, elevated white blood cell count, and some may have leukemia-like reaction. Mild patients tend to have moderate fever, while severe patients may have high fever.
2. Diarrhea
Diarrhea is a prominent symptom of the disease. Due to mucosal inflammation and exotoxin stimulation impairs the absorption function of the diseased intestinal canal, affects the intestinal absorption of intestinal contents, makes the intestinal wall to the intestinal lumen of the secretion of water, sodium increase, liquid infiltration into the intestinal lumen, resulting in a large amount of intestinal fluid accumulation caused by diarrhea. The degree of diarrhea depends on the number of bacteria, the size of virulence and the resistance of the patient. In mild cases, dilute stools or watery stools several times a day can be cured by stopping the original antibiotics and putting in targeted drugs; in severe cases, severe diarrhea occurs, and pusy mucous blood stools with a fishy odor are discharged, which can be as many as 20-30 times a day, and the amount of stools discharged can be up to 4000 ml per day, or even up to 10000 ml per day. blood or plaque-like pseudomembrane is present in the feces from time to time, and the infection of Staphylococcus aureus tends to be grassy-green. Infection with Staphylococcus aureus is often grass-green watery stool, and Clostridium difficile can be yellow egg-shaped dilute watery stool. If toxic intestinal paralysis can not eliminate the large amount of fluid accumulated in the intestinal lumen, the number of diarrhea instead of reducing, but the disease becomes more serious. Diarrhea usually stops 5 to 8 days after stopping the drug, and individual can last 2 to 3 weeks or even two months. Diarrhea can be divided into two types: one is a large number of green watery stools, which can be similar to cholera. Every day in the amount of 4000 ~ 5000ml, resulting in a large loss of body fluids, causing dehydration and electrolyte disorders, and then by the absorption of bacteriophage and necrotizing histamine and metabolic poisoning. Patients often appear shock, at this time there can be oliguria, and even the manifestation of Ming functional insufficiency. Another type of yellow-green mucus stool, 3 to 4 times a day, more than 10 times, the amount of small, part of the blood stool.
3. Abdominal pain and bloating
Under the stimulation of inflammation and intestinal fluid toxins, the intestinal tube is spasmodic contraction, thus causing different degrees of abdominal pain, and in severe cases, the pain can be very severe with early bowel sound hyperpronunciation. The peristaltic dysfunction of the intestinal tubes does not allow effective evacuation of the fluid and gases that accumulate in the intestines, leading to abdominal distension. Pseudomembranous enteritis is different from normal diarrhea in that it is accompanied by frequent diarrhea with abdominal distension. In severe cases, there may be typical symptoms of toxic megacolon, and in more severe cases, there is abdominal pain, bloating, intestinal patterning, full abdominal muscle resistance and pressure, and diminished or absent bowel sounds. Those with intestinal necrosis, perforation appear diffuse peritonitis, the whole abdominal muscles appear obvious resistance, pressure pain rebound pain, abdominal distension is more obvious, the systemic symptoms of toxicity is more serious, so as to fall into infectious toxic shock. Some patients have ascites.
4. Toxemia and shock
It is the manifestation of the late stage of severe patients. After the absorption of a large number of toxins, there is obvious loss of appetite, high fever, tachycardia, depression, delirium, disorientation, impaired consciousness, shortness of breath, cold hands and feet, unstable blood pressure, etc., which finally leads to liver and renal insufficiency and irreversible shock. Individual patients have a rapid onset of illness, mainly manifested by high fever, severe abdominal distension, vomiting blood, blood in stool, shock and death within a few hours.
Examination
1. Stool routine
Microscopic examination of fecal smear will be helpful for clinical judgment if gram-positive bacilli and their germ cells are found. Subsequently, a staged bacterial culture can be performed to check for large numbers of gram-positive bacteria. Stool is positive for occult blood test when pus cells and leukocytes are seen microscopically.
If available, the presence of Clostridium difficile antibiotic in the stool can be determined by the two-enzyme Clostridium difficile antibiotic neutralization assay. The cytotoxic effect of cell-free fecal filtrate produced in tissue culture can be neutralized by antimycotics and can be used to help establish the diagnosis.
2. Bacteriologic examination
Clostridium difficile is cultured in the feces at presentation in 90% of cases.
3. Cytotoxicity tests
Diluted stool or bacterial culture filtrate has specific cytopathic effects on tissue culture cells (HELA), which can be neutralized by the antitoxin of Clostridium difficile, thus confirming that Clostridium difficile is a toxin-producing strain.
4. Detection of toxin A
Toxin A can be examined by convection immunoelectrophoresis, enzyme-linked immunosorbent assay, latex agglutination assay and monoclonal antibody method.
5. Other auxiliary examinations
(1) Colonoscopy Pseudomembranous enteritis that also invades the colon, especially the sigmoid colon, can be examined with the aid of colonoscopy. Typical manifestations of mucosal redness and edema, above the plaque or fusion of the pseudomembrane, biopsy of the mucosa can be seen with acute inflammation, pseudomembrane containing necrotic epithelium, fibrin, inflammatory bacteria, and so on. Application of fiberoptic colonoscopy to grasp the stage of disease progression, enteritis has not yet formed a pseudomembrane or localized pseudomembrane has been detached when the pseudomembrane under the microscope may not be able to find the pseudomembrane, so it is not necessarily to pseudomembrane for the only diagnostic basis, the failure to see the pseudomembrane does not necessarily exclude the disease. Pseudomembranous enteritis lesions can be distributed in a jumping pattern, in order to prevent the omission of small lesions, the scope of microscopy must include the whole colon, take lesions in representative parts, and take biopsies with a certain depth.
(2) Abdominal X-ray radiographs often show thickening of the intestinal mucosa, distension of the small intestine, and intestinal obstruction in some patients with intestinal paralysis. Barium enema may reveal brush border, fingerprinting and scattered round and irregular filling defects. Gas-barium double contrast may provide additional diagnostic indicators, but must be performed carefully to prevent bowel perforation.
(3) Ultrasonography Ultrasonography can detect localized intestinal wall pseudomembrane, heavy thickening due to mucosal and submucosal edema, narrowing or disappearance of the intestinal lumen, and pseudonephridium, which seems to be intestinal tuberculosis or tumor, can be found in the right lower abdomen on careful exploration. A well-equipped ultrasound diagnostic machine can also more accurately distinguish the levels associated with the lesion. In addition, ultrasonography can detect ascites associated with the disease.
(4) CT examination CT is not specific, and may occasionally reveal a thickened bowel wall with low attenuation.
(5) Blood biochemical examination Electrolyte disorders can be seen, often with low potassium, low sodium and hypoproteinemia. Serum albumin should be less than 3%, and the white blood cell count can be as high as 20×109/L or more, with neutrophils predominating.
Diagnosis
1. There is a history of certain antibiotic use prior to diarrhea.
2. There are typical clinical manifestations such as diarrhea, abdominal distension, fever, increased white blood cell count, and in severe cases, blood in stool, toxic intestinal paralysis, intestinal perforation, and toxic shock.
3. Fecal bacteriological isolation and identification of Clostridium difficile.
4. Fecal filtrates or filtrates from culture of isolated strains have toxins that have cytopathic effects in tissue culture and are neutralized by Clostridium difficile antitoxin or Clostridium sludge antitoxin.
Differential Diagnosis.
In the clinical diagnosis of pseudomembranous enteritis, care should be taken to differentiate it from the following conditions
1. Intestinal torsion or intussusception after repositioning surgery
Intestinal torsion or intussusception causes ischemia and hypoxia of the intestinal tube, and after the blood circulation improves, high fever and diarrhea appear due to the absorption of toxins, which sometimes need to be differentiated from pseudomembranous enteritis. The diarrhea that occurs after reversal of intestinal torsion or intussusception comes from the accumulated contents of the intestinal tract. The frequency and amount of diarrhea is less than that of pseudomembranous enteritis and does not become more and more frequent, and the contents contain more active ingredients than those of pseudomembranous enteritis, and the overall tendency is toward gradual remission, although transient systemic toxicity can be present. The stools will not be typically watery, much less pseudomembranous, and the bacterial smear or culture will not be dominated by cocci, nor will there be Clostridium difficile.
2. Ulcerative colitis
Ulcerative colitis often has a long history of diarrhea, severe cases can have more than ten times a day watery stools, a few acute onset of acute onset, there can be severe systemic toxaemia, extensive colonic lesions can be toxic megacolon manifestations, until the occurrence of intestinal perforation and diffuse peritonitis. The lesions of ulcerative colitis are mainly in the colon and rectum, lack of pseudomembranous enteritis as the causative agent, and have a tendency to recur, there is no pseudomembrane and related pathogens in the fecal examination, and the mucous membranes are characterized by multiple ulcers and polyps, and the X-ray and colonoscopy can help to make the diagnosis.
3. Crohn’s disease
Crohn’s disease is most common in 20-40 years old, the incidence of men and women is roughly equal, acute onset of ileum congestion and edema, mesenteric thickening lymph node enlargement, fever, abdominal pain, mass and perforation can occur. Crohn’s disease has a long course, with intermittent episodes of mild to severe symptoms, less severe diarrhea, and often unformed loose stools with no pseudomembrane formation, unrelated to the use of antibiotic drugs. Barium meal and barium enema, colonoscopy and tissue biopsy are needed to confirm the final diagnosis.
4. Hemorrhagic necrotizing enterocolitis
Hemorrhagic necrotizing enterocolitis is related to ischemic injury of intestinal mucosa and bacterial infection. It is more common in infants and children, and is more common in males than females, and the lesions are mainly in the small intestine, and the intestinal mucosa is in stages of congestion, edema, hemorrhage and necrosis, which may be accompanied by inflammation of the mesentery and lymph nodes belonging to the intestinal mucosa. There may be acute abdominal colic, diarrhea, blood in stool and toxemia, and the feces have a special fishy odor. Systemic failure, chills, fever, elevated white blood cell count with leftward shift of the nucleus, and the appearance of toxic granules and other manifestations of toxemia occur within 1 to 2 days of the onset of the disease. Mild hemorrhagic necrotizing enterocolitis is not easy to distinguish from pseudomembranous enterocolitis when there is only diarrhea and only a small amount of bloody watery stool. It may cause toxic shock, toxic megacolon, intestinal paralysis, hemorrhagic necrosis of the intestinal wall and even intestinal perforation.
Treatment
The goal of treatment is to eliminate bacteria, eliminate or weaken the effect of bacterial toxins, foster the normal intestinal flora, and improve the symptoms of the general body and abdominal digestive tract.
1. Treatment of etiology
Extremely important, clinical use of drugs should strictly grasp the indications for the extensive use of broad-spectrum antibiotics to closely observe the changes in the digestive tract. Once the disease is suspected or a clear diagnosis has been made, the antibiotics being used should be stopped immediately. Discontinuing antibiotics will favor the growth of other intestinal bacteria, especially aerobic bacteria, inhibit the growth of anaerobic bacteria, and restore the normal intestinal environment.
2. Application of antibiotics
Before the results of stool culture and drug sensitivity test should be promptly changed to antibiotics, can use targeted narrow-spectrum antibiotics.
(1) Erythromycin Erythromycin can be given orally and intravenously if Staphylococcus aureus is the etiologic agent, and the course of treatment is 7-10 days.
(2) Vancomycin Vancomycin has antimicrobial activity against Clostridium difficile, is rarely absorbed in the intestinal tract, maintains high drug concentration, has few systemic toxic side effects, and is also effective against Staphylococcus aureus, so it has been clinically recognized as the first choice of drug for the treatment of this disease. However, a small number of patients have relapsed after stopping the drug for symptomatic relief.
(3) Metronidazole Metronidazole is also often used in the treatment of this disease, and get more satisfactory efficacy. In vitro experiments of metronidazole on Clostridium difficile has a very good inhibitory effect, the disadvantage is that the drug is easy to be absorbed when taken orally, the concentration of the intestinal tract is relatively low, the use of the need to increase the dose. Can not be taken orally can be given intravenously, individual cases of metronidazole can also become the cause of pseudomembranous enteritis, but still not a good therapeutic drug.
(4) Sulfaguanidine and phthalosulfathiazole Oral for 7 to 10 days.
(5) Mycopeptides Treatment with mycopeptides and Zeomicin has also been reported. Mycopeptide is a peptide with activity on cell wall, and it can inhibit Clostridium difficile in vitro. As with vancomycin, it is less absorbed from the gastrointestinal tract when given orally, and larger concentrations can be obtained in the feces, with fewer systemic toxic side effects.
3. Antitoxins inhibit the pathogenic effects of toxins
(1) Cholestyramine Cholestyramine can bind the cytotoxicity and enterotoxicity of Clostridium difficile in vitro, and this drug can play the role of ion exchange resin in the intestinal tract to bind with Clostridium difficile in the intestinal tract and excrete out of the intestinal tract, which can block or reduce the histotoxicity and vitality of the toxin and promote the absorption of bile salts in the terminal part of the ileum to alleviate the symptoms. Anticholinergic is suitable for mild cases or those that relapse after successful initial treatment, and those that relapse after dose reduction with vancomycin.
(2) Clostridium difficile polyvalent antitoxin for gas gangrene Add to 5% dextrose solution IV drip until satisfactory results are achieved.
(3) Kaurenamine This drug binds to the toxin and reduces absorption.
4. Support normal flora
Since the loss of resistance to intestinal colonization by Clostridium difficile is an important factor in the pathology of pseudomembranous enteritis, it is theoretically possible to treat it by reestablishing normal flora. Lactasepsin, vitamin C, folic acid, vitamin B complex, vitamin B12, and glutamic acid promote the normal flora of Coccidioides intestinalis. Lactose, honey, maltose, etc. promote the propagation of E. coli.
5. Symptomatic and systemic supportive treatment
(1) Anti-shock and treatment for toxemia Replenish blood volume and give whole blood, plasma or albumin to enhance resistance and anti-shock ability. Treatment of toxemia can be applied for a short period of time. Adrenocorticotropic hormones with a view to achieving a reduction in toxemia and favoring the correction of shock. However, there is no need for large doses and long-term use. Low blood pressure can be used with vasoactive drugs such as dopamine and mesalamine.
(2) Correct water and electrolyte disorders and acid-base balance imbalance Diarrhea can lead to dehydration, generally isotonic dehydration, should be based on biochemical tests and urine output to replace the lost water and potassium, sodium salt. Alkalizing drugs should be used to correct acidosis. It is often difficult to replenish the blood volume by intravenous fluid supplementation alone, and when there is still normal mucous membrane in the intestines that can absorb water, glucose saline can be replenished by oral route. Glucose can be absorbed as a carrier of sodium ions while being absorbed, which is conducive to replenish the loss of sodium and the restoration of acid-base balance.
(3) Parenteral nutrition (PN) treatment This disease has severe diarrhea, affects feeding during the course of the disease, and has a long duration of the disease, which often tends to lead to a negative nitrogen balance. Therefore, PN treatment can enhance the body’s ability to resist the disease and accelerate tissue repair.
(4) Treatment of underlying diseases In the course of treatment, attention should be paid to the treatment of underlying diseases, correction of heart failure, improvement of liver function and so on.
(5) Other treatments Try antispasmodics. Individual reports have tried hormones in severely ill patients, and adrenocorticotropic hormone can be applied if necessary. Some advocate a trial of anticholinergic amines (cholestyramine). It exerts an ion-exchange effect in the intestines binding to Clostridium difficile and is excreted, and may promote absorption of bile salts in the terminal ileum to improve diarrhea. Take 4g orally every 6 hours for 5 days. If there is persistent diarrhea with hypoproteinemia and electrolyte disorders or toxic colonic dilatation, surgical decompression with transverse colostomy is necessary. Antidiarrheal agents are contraindicated to avoid inducing toxic colonic dilatation. For severe postoperative malnutrition, intravenous high-nutrition drip therapy can be given.
6. Surgical treatment
If there is no improvement in the course of the disease under active non-surgical treatment, and if there is suspicion of intestinal necrosis, intestinal perforation or occurrence of toxic megacolon, the patient can have active surgical exploration while correcting acidosis and replenishing blood volume.
(1) Small bowel repair or resection is suitable for localized or segmental intestinal lesions, intestinal wall congestion and edema, necrosis and perforation. Repair or one-stage resection anastomosis can be performed as appropriate.
(2) Ileostomy and transverse colostomy In toxic megacolon or intestinal perforation, due to the critical condition and poor systemic condition, it is not easy to withstand a larger operation, feasible to have a terminal ileostomy or transverse colostomy, and at the same time, it can be instilled with vancomycin or metronidazole through the stoma.
Questions you may be concerned about
What is the drug of choice for pseudomembranous enteritis
Pseudomembranous enteritis is also known as pseudomembranous enteritis, and vancomycin is preferred for the treatment of pseudomembranous enteritis.
Pseudomembranous enteritis is mostly due to the long-term use of antibiotics in large quantities, causing intestinal flora imbalance and leading to the rapid reproduction of Clostridium difficile, the production of mycotoxin and triggered the disease to diarrhea, fever, nausea, vomiting, etc. as the main clinical manifestations.
Vancomycin is a glycopeptide antibiotic, can have antibacterial activity against Clostridium difficile, can be used in the intestinal infections caused by Clostridium difficile, but may cause nausea, phlebitis, tinnitus, renal impairment and other adverse reactions, and at the same time, is prohibited for those who are allergic to vancomycin antibiotics.
Suffering from pseudomembranous enteritis, you need to consult a doctor in time for examination and choose the appropriate treatment drugs according to your own situation. The use of medication needs to be under the guidance of a doctor.
Prognosis
Most patients can be cured after treatment. In mild cases, some patients can recover spontaneously. Very few patients improve after treatment, but diarrhea can occur again. The mortality rate for severe cases, especially for elderly patients after intestinal surgery, can reach 50% to 70%. In recent years, due to timely diagnosis and treatment, the mortality rate has been reduced to less than 30%.