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Previous Volume 355:2418-2426 December 7, 2006 Number 23 Next

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ABSTRACT

Background Antibiotic-associated hemorrhagic colitis is a distinct form of antibiotic-associated colitis in which Clostridium difficile is absent. Although the cause is not known, previous reports have suggested a role of Klebsiella oxytoca.

Methods We studied 22 consecutive patients who had suspected antibiotic-associated colitis and who were negative for C. difficile. Patients underwent diagnostic colonoscopy, and among those who received a diagnosis of antibiotic-associated hemorrhagic colitis, stool samples were cultured for K. oxytoca. We isolated K. oxytoca strains and tested them for cytotoxin production using a tissue-culture assay. In addition, we also cultured stool samples obtained from 385 healthy subjects for K. oxytoca. An in vivo animal model for antibiotic-associated hemorrhagic colitis was established with the use of Sprague-Dawley rats.

Results Of the 22 patients, 6 had findings on colonoscopy that were consistent with the diagnosis of antibiotic-associated hemorrhagic colitis, and 5 of these 6 patients had positive cultures for K. oxytoca. No other common enteric pathogens were found in the five patients. Before the onset of colitis, all five were receiving penicillins, and two were also taking nonsteroidal antiinflammatory drugs (NSAIDs). All isolated K. oxytoca strains produced cytotoxin. K. oxytoca was found in 1.6% of the healthy subjects. In the animal model, K. oxytoca was found only in the colon of rats that received amoxicillin–clavulanate in addition to being inoculated with K. oxytoca. In these rats, infection with K. oxytoca induced a right-sided hemorrhagic colitis that was not observed in uninfected animals that received amoxicillin–clavulanate, indomethacin (an NSAID), or both.

Conclusions Our fulfillment of Koch's postulates for cytotoxin-producing K. oxytoca suggests that it is the causative organism in at least some cases of antibiotic-associated hemorrhagic colitis. Infection with K. oxytoca should be considered in patients with antibiotic-associated colitis who are negative for C. difficile.

Source Information

From the Department of Internal Medicine (C.H., R.K., N.G., G.J.K., T.A.H.), the Institute of Pathology (C.L., G.G.), and the Institute of Experimental and Clinical Pharmacology (E.B., I.T.L., R.S.), Medical University of Graz, Graz, Austria.

Address reprint requests to Dr. Högenauer at the Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria, or at christoph.hoegenauer{at}meduni-graz.at.

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