Antibiotic-associated diarrhea is a disease characterized by the appearance of an unformed stool during or after taking antibacterial drugs. The disease is accompanied by dyspeptic symptoms (easing of stool, gas formation). In severe cases, intense abdominal pain, weakness, fever appear. Diagnosis is based on establishing the connection of taking AB with the development of diarrhea. In addition, fecal analysis and endoscopic examination of the intestine are carried out. Treatment involves the abolition of AB, the appointment of probiotics and detoxification drugs. When the causative agent of the disease is detected, etiotropic antibacterial therapy is performed.
Antibiotic-associated diarrhea (AAD, nosocomial colitis) – three or more episodes of loose stools, repeated for at least two days and associated with taking antibacterial drugs (AB). The disorder can manifest itself within 4 weeks after AB withdrawal. In developed countries, intestinal damage is the most common reaction to antibiotic therapy: in people taking antibiotics, AAD occurs in 5-30% of cases. Pathology occurs both in a mild self-canceling form and in the form of severe prolonged colitis. In modern gastroenterology, at least 70% of cases of the disease are idiopathic AAD, 30% – Clostridium difficile-associated diarrhea. The disease affects men and women equally.
Causes of antibiotic-associated diarrhea
Antibiotic-associated diarrhea often develops after the administration of penicillin antibiotics, tetracyclines, cephalosporins. The method of administration of medications practically does not affect the likelihood of diarrhea. When taken orally, medications affect the mucous layer of the gastrointestinal tract. In the parenteral route of administration, AB metabolites are excreted with bile and saliva, affecting the obligate microflora. Taking into account the causes of the disease , there are 2 forms of AAD:
- Idiopathic (IAAD). It develops as a result of the negative impact of AB on the eubiosis of the gastrointestinal tract. The influence of pathogenic microorganisms on the gastrointestinal tract is one of the possible causes of the development of this disease. Among the variety of pathogens, staphylococci, proteas, enterococci, clostridias, fungi are often found. The risk of AAD increases with prolonged (more than 10 days), frequent and incorrect administration of AB (excess dose).
- Clostridium difficile-associated diarrhea (C. difficile-AD). Etiologically, it is associated with a violation of the microflora and excessive colonization of the gastrointestinal tract by opportunistic bacteria Clostridium difficile. Dysbiosis occurs as a result of taking AB from the group of cephalosporins, amoxicillin, lincomycin. There are cases of development of intrahospital antibiotic-associated infection by transmission of the pathogen through personal hygiene products (towels, soap, dishes), medical instruments with poor-quality processing.
In addition to the direct effects of antibacterial agents on the intestinal wall, there are risk factors that increase the likelihood of developing the disease. These include childhood and old age, the presence of severe somatic pathology (heart, renal failure), uncontrolled administration of antacid drugs, congenital and acquired immunodeficiency conditions, surgical interventions on the abdominal cavity, probe nutrition. Chronic gastrointestinal diseases (Crohn’s disease, nonspecific ulcerative colitis) also contribute to the emergence of antibiotic-associated colitis.
Antimicrobials reduce the growth and reproduction of not only pathogenic, but also symbiotic microorganisms. There is a decrease in the obligate intestinal microflora, dysbiosis develops. This fact underlies the pathogenesis of both types of antibiotic-associated diarrhea. In the idiopathic form, an increase in intestinal motility, a toxic lesion of the mucous membrane or a violation of metabolic processes in the intestine also plays a role.
Antibiotic-associated clostridial colitis occurs due to changes in the composition of the endogenous normoflora of the gastrointestinal tract when taking cephalosporins of the III and IV generation, fluoroquinolones, penicillins. Dysbiosis promotes the reproduction of C. Difficile, which in large quantities secrete 2 types of toxins (A and B). Being in the lumen of the gastrointestinal tract, enterotoxins destroy epithelial cells and cause inflammatory changes in the intestinal wall. Colitis mainly affects the large intestine with the formation of diffuse hyperemia and swelling of the mucosa. The wall of the gastrointestinal tract thickens, fibrin deposits form, having the appearance of yellowish plaques (pseudomembranes).
There are two forms of idiopathic antibiotic-associated diarrhea: infectious and non-infectious. Among the pathogens of the infectious form of AAD, clostridium perfringens, Staphylococcus aureus, Salmonella, Klebsiella, Candida fungi are often found. Non – infectious IAAD is represented by the following types:
- Hyperkinetic. Clavulanate and its metabolites increase the motor activity of the gastrointestinal tract, taking macrolides causes a contraction of the duodenum and antrum of the stomach. These factors contribute to the appearance of an unformed chair.
- Hyperosmolar. It develops due to partial absorption of AB or with a violation of carbohydrate metabolism. Carbohydrate metabolites accumulate in the intestinal lumen, which cause increased secretion of electrolytes and water.
- Secretory. It is formed due to the violation of intestinal eubiosis and deconjugation of bile acids. Acids stimulate the release of water and chlorine salts into the intestinal lumen, the consequence of these processes is frequent unformed stools.
- Toxic. It is formed due to the negative effects of penicillin and tetracycline metabolites on the intestinal mucosa. Dysbiosis and diarrhea develop.
Manifestations of C. difficile-BP can vary from asymptomatic carrier to rapidly developing and severe forms. Depending on the clinical picture and endoscopy data, the following types of antibiotic-associated clostridial infection are distinguished:
- Diarrhea without colitis. It is manifested by an unformed stool without intoxication and abdominal syndromes. The intestinal mucosa is not changed.
- Colitis without pseudomembranes. It is characterized by a detailed clinical picture with moderate dehydration and intoxication. During endoscopic examination, catarrhal inflammatory changes in the mucous membrane are observed.
- Pseudomembranous colitis (PMC). This disease is characterized by severe intoxication, dehydration, frequent watery stools and abdominal pain. During colonoscopy, fibrinous plaque and erosive-hemorrhagic changes in the mucosa are determined.
- Fulminant colitis. The most severe form of antibiotic-associated gastrointestinal disorder. Develops at lightning speed (from several hours to a day). Causes serious gastroenterological and septic disorders.
Symptoms of antibiotic-associated diarrhea
In idiopathic antibiotic-associated diarrhea, symptoms occur during (in 70% of patients) or after discontinuation of antibiotic treatment. The main, sometimes the only, manifestation of the disease is an unformed stool up to 3-7 times a day without admixtures of blood and pus. Rarely there are pains and a feeling of swelling in the abdomen, flatulence due to the increased work of the gastrointestinal tract. The disease proceeds without an increase in body temperature and symptoms of intoxication.
Unlike the idiopathic form, the clinical spectrum of manifestations of Clostridium difficile-AD varies from asymptomatic colitis to severe fatal forms of the disease. Bacterial carrier is expressed by the absence of symptoms and the release of clostridium feces into the environment. The mild course of the disease is characterized only by liquid stools without fever and pronounced abdominal syndrome. C. is more often observed . difficile-associated colitis of moderate severity, which is manifested by an increase in body temperature, periodic cramping pains in the umbilical region, multiple diarrhea (10-15 times / day).
The severe course of the disease (PMT) is characterized by frequent (up to 30 times / day) profuse watery stools with a fetid odor. Feces may contain impurities of mucus and blood. The disease is accompanied by intense abdominal pain, which disappears after the act of defecation. Patients have a deterioration in their general condition, marked weakness and fever up to 38-39 ° C. In 2-3% of cases, a fulminant form of the disease is registered, which is manifested by a rapid increase in symptoms, severe intoxication and the appearance of early severe complications of antibiotic-associated diarrhea.
Idiopathic AAD responds well to treatment and does not cause complications in patients. Diarrhea caused by C.difficile leads to a persistent decrease in blood pressure, the development of electrolyte disorders and dehydration of the body. The loss of protein and water contribute to the appearance of edema of the lower extremities and soft tissues. Further development of the disease provokes the appearance of megacolon, manifestations of the gastrointestinal mucosa up to perforation of the colon, peritonitis and sepsis. The lack of timely diagnosis and pathogenetic treatment leads to death in 15-30% of cases.
If there is abundant loose stools and abdominal discomfort that cause suspicion of the development of antibiotic-associated diarrhea, a gastroenterologist’s consultation is required. A specialist with the help of studying the anamnesis of life and disease, physical examination, laboratory and instrumental examination data will make an appropriate conclusion.
To diagnose idiopathic antibiotic-associated diarrhea, it is sufficient to identify the relationship between taking AB and the onset of diarrhea, and exclude concomitant gastrointestinal pathology. In this case, laboratory indicators remain normal, there are no changes in the intestinal mucosa. If Clostridium difficile-associated diarrhea is suspected, the following methods are used to confirm the diagnosis:
- Blood test. In the general blood test, leukocytosis, increased ESR, anemia are noted; in the biochemical, hypoproteinemia.
- Fecal examination. Leukocytes and erythrocytes are detected in the coprogram. The main diagnostic criterion of the disease is the detection of the pathogen in the feces. The diagnosis of choice is a cytopathogenic test (CT) and a toxin neutralization reaction (TNR), which determine toxin B. The method of enzyme immunoassay (ELISA) is sensitive to A and B-endotoxins. Polymerase chain reaction (PCR) is used to identify genes encoding toxins. The culture method makes it possible to detect clostridium in fecal culture.
- Colon endoscopy. Colonoscopy is performed to visualize pathological changes in the intestine (pseudomembranes, fibrin films, erosions). Endoscopic diagnosis in severe colitis can be dangerous due to the risk of perforation of the intestine.
Diagnosis of antibiotic-associated stool disorder usually does not cause difficulties. The idiopathic form of the disease is differentiated with mild food toxicoinfections. The clinic of C. difficile-associated diarrhea, namely pseudomembranous colitis, may resemble the course of cholera, Crohn’s disease, ulcerative colitis and severe food poisoning. Additionally, an overview abdominal x-ray, CT of the large intestine is performed.
Antibiotic-associated diarrhea treatment
Treatment of non-clostridial antibiotic-associated diarrhea involves the cancellation or reduction of the dose of antibacterial agents, the appointment of antidiarrheal drugs (loperamide), eubiotics and probiotics (lactobacilli, bifidobacteria). With multiple episodes of loose stools, it is advisable to normalize the water-salt balance.
Detection of clostridium difficile is an indication for the cancellation of AB and the appointment of etiotropic, symptomatic and detoxification therapy. The drug of choice for the treatment of the disease is metronidazole. In severe cases and with intolerance to metronidazole, vancomycin is prescribed. Correction of dehydration and intoxication is carried out by parenteral administration of water-salt solutions (acesol, Ringer’s solution, rehydrone, etc.).
The complex therapy of clostridial colitis includes the use of enterosorbents, probiotics. The latter are prescribed after etiotropic therapy to restore the normal intestinal flora for a course of 3-4 months. With complications of PMK (intestinal perforation, megacolon, recurrent progressive course of colitis), surgical treatment is indicated. Resection of part or the entire colon is performed (hemicolectomy, colectomy).
Prognosis and prevention
The prognosis of idiopathic AAD is favorable. The disease can be stopped independently after the withdrawal of antibiotics and does not require specific treatment. With timely diagnosis and adequate treatment of pseudomembranous colitis, a full recovery can be achieved. Severe forms of diarrhea, ignoring the symptoms of the disease can lead to complications from both the gastrointestinal tract and the whole body.
Rational antibiotic therapy involves taking medications for strict indications only when prescribed by a doctor and under his careful supervision. Prevention of antibiotic-associated diarrhea includes the use of probiotics to maintain normal gastrointestinal microflora, rational nutrition and maintaining an active lifestyle.