The relationship between an increase in beta-lactamase activity after oral administration of three new cephalosporins and protection against intestinal ecological disturbances.
Forty-four healthy volunteers were given either amoxycillin (ten subjects), cefpodoxime proxetil (ten subjects), ceftibuten (14 subjects) or cefuroxime axetil (ten subjects) orally for 7-10 days, in order to study the ecological effects on the intestinal microflora. In all three groups receiving oral cephalosporins there was a significant increase in beta-lactamase activity during administration (P < 0.05). There was also an inverse correlation between enzyme activity in faeces during administration compared with the concentration of drug in the intestines and the level of ecological disturbance in the normal intestinal microflora. In volunteers given amoxycillin, only small alterations in the faecal microflora were observed although overgrowth by new amoxycillin resistant enterobacteria occurred in all volunteers. There was an overgrowth of enterococci and yeasts during treatment with cefpodoxime proxetil, ceftibuten or cefuroxime axetil, whereas the numbers of enterobacteria were reduced. Colonization with resistant enterobacteria did not occur, but 14 of 34 subjects receiving oral cephalosporins were colonized by Clostridium difficile. Side-effects were mild and not associated with the ecological alterations in the intestinal microflora.
Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Sweden.
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Stark
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Nord
D000284:Administration, Oral; D000328:Adult; D000658:Amoxicillin / Q000009:adverse effects / Q000494:pharmacology*; D000077722:Ceftibuten; D015296:Ceftizoxime / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D002444:Cefuroxime / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D002511:Cephalosporins / Q000009:adverse effects / Q000494:pharmacology*; D005243:Feces / Q000737:chemistry / Q000201:enzymology / Q000382:microbiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000009:adverse effects / Q000494:pharmacology*; D001618:beta-Lactamases / Q000187:drug effects / Q000378:metabolism*; D000097627:Cefpodoxime Proxetil
D000658:Amoxicillin; D000077722:Ceftibuten; D015296:Ceftizoxime; D002444:Cefuroxime; D002511:Cephalosporins; D011355:Prodrugs; D001618:beta-Lactamases; D000097627:Cefpodoxime Proxetil; C040738:cefuroxime axetil