The antibiotic-associated hemorrhagic colitis is a serious bowel inflammation, which usually occurs under a penicillin therapy and is not caused by Clostridium difficile. This form of Antibiotikakolitis has been little attention in the medical literature and therefore in routine clinical seldom diagnosed and often misinterpreted. In a recent publication in the NEJM our group could now prove the bacterium Klebsiella oxytoca as a cause.
The incidence of diarrhea is a common side effect that occurs during or after treatment with antibiotics. Mostly it is a little functional diarrhea. This is caused by changes in the colonic flora and with the completion of Antibiotikiatherapie self-limiting. 10-20% of diarrhea with antibiotics be triggered by an infection with Clostridium difficile. The spectrum of Clostridium difficile infection ranges from an asymptomatic carrier state of mild diarrhea to the severe symptoms of pseudomembranous colitis. In recent years led rising infection levels and a new strain with higher virulence and mortality in an increased interest in this infection. A far less acclaimed disease is antibiotic-associated hemorrhagic colitis, a severe intestinal inflammation that is not triggered by C. difficile. Although this disease has already been described for almost 30 years, the cause was unclear. An allergy to penicillin or a circulatory disorder in the intestine have been postulated.
Antibiotic-associated hemorrhagic colitis
The antibiotic-associated hemorrhagic colitis is referred to in the literature as segmental hemorrhagic antibiotic colitis or penicillin-associated right side Antibiotikakolitis. The disease usually occurs in young patients on penicillin therapy, however, with other antimicrobial agents such as Cephalosporins occur. Usually it takes a few days after initiation of antibiotic therapy on the occurrence of severe abdominal cramps and bloody diarrhea.
In a recent publication, the bacterium Klebsiella oxytoca as trigger this form of Antibiotikakolitis now able to identify our group in Graz. In a group of patients with antibiotic-associated haemorrhagic colitis the bacteria K. oxytoca was found in almost all patients. In an appropriate animal model, it is then able to reproduce the disease by K. oxytoca and to isolate the germ in the case of simultaneous administration of antibiotics in the gut of the animals. The classic Koch's postulates, which prove that a disease is caused by a specific germ, could therefore be met by this work. Furthermore, the isolated from patients K. oxytoca strains showed Zytotoxinproduktion that was not found in other tribes. The cytotoxin solves ultimately colitis from about damage to the cells in the intestine.
K. oxytoca is a facultative anaerobic gram-negative rod, belonging to the group of Enterobacteriaceae (like E. coli). K. oxytoca caused as K. pneumoniae especially nosocomial infections of the respiratory tract, soft tissue infections, and urogenital and hepatobiliary infections. The germ is ubiquitous in the environment and can be found on mucous membranes and intestines Healthy. In Austria, the germ was detected in 2% of the healthy population in the gut. 98% of isolates of K. oxytoca have ampicillin / amoxicillin resistance on by a chromosomal lactamase. By antibiotic therapy occurs in patients for selection and overgrowth of this germ in the intestinal flora, and finally to the formation of colitis.
In a recent study, we addressed the question of the causal agents in antibiotic-associated enteric disease after. The gram-negative pathogens K. oxytoca was detected both in the stool of patients with hemorrhagic colitis, and in 1.6% of healthy subjects.
Five out of six patients with the confirmed diagnosis colonoscopy "antibiotic-associated hemorrhagic colitis" had positive cultures for K. oxytoca. There has been no pathogens found in feces in the affected patients. Before the outbreak of colitis, all five patients were treated with penicillin antibiotics. The researchers also suspect a connection with the Einnnahme of non steroidal anti-inflammatory drugs, who took two of the patients prior to the examinations. For the culturally cultured Klebsiella oxytoca strains producing cytotoxin was detected.
In animal studies, rats were infected with Klebsiella oxytoca and treated with amoxicillin-clavulanic acid and indomethacin. In animals in which Klebsiella oxytoca was detected in the colon, was a right-sided colitis haemorrhagic be detected. Animals were negative for Klebsiella oxytoca, the disease did not develop, suggesting the pathogenicity of the pathogen as a triggering agent.
The new findings for zytotoxinbildende K. oxytoca suggests that this is the causative agent of antibiotic-associated hemorrhagic colitis, at least in some cases. Patients with antibiotic-associated colitis who are negative for C. difficile, should be examined down to infection with K. oxytoca.
Diagnosis and differential diagnosis of C. difficile-associated colitis
The antibiotic-associated hemorrhagic colitis is distinguished clinically and endoscopically from that caused by Clostridium difficile Antibiotikakolitis. The antibiotic-associated hemorrhagic colitis usually occurs in young, outpatients on after a brief penicillin therapy. Patients often take an additional NSAID. Symptoms include bloody diarrhea and abdominal cramps often massive. When associated diarrhea C. difficile elderly, hospitalized and often multimorbid patients are mostly affected. The most common triggers are antibiotics broadband penicillins, cephalosporins, clindamycin, and the 3rd and 4th generation gyrase. The diarrhea is usually not bloody, although they can be quite severe. Endoscopy can be found in the antibiotic-associated hemorrhagic colitis a segmental infestation especially of the right colon, typically is a mucosal edema with haemorrhages, oblong ulcers are sometimes observed. Often, colitis is sonographically detected. Unlike almost always shows up at the C. difficile-associated Antibiotikakolitis a continuous involvement of the rectum and left colon, which may extend to the involvement of the entire colon. Endoscopic pathognomonic are pseudo membrane, but may also be the image of a non-specific colitis.
The diagnosis of antibiotic-associated hemorrhagic colitis results from the clinical and endoscopic image. Detection of Klebsiella oxytoca in the stool culture can be performed by any bacteriological laboratory in principle. So far has not been tested for this germ in stool because he was considered part of the normal intestinal flora. The Zytotoxinproduktion individual strains can be determined by our laboratory in Graz on request.
The treatment of choice for the antibiotic-associated hemorrhagic colitis is the discontinuation of the triggering antibiotic. Then there is a restitutio ad integrum. In severe cases, a therapeutic success is described with quinolones in the literature.
Patients with antibiotic-associated haemorrhagic colitis treated initially on suspicion of C. difficile infection with metronidazole, which has no activity against K. oxytoca seem to have no unfavorable clinical course.