Pharmacokinetics and antibacterial efficacy in vivo of beta-lactam combinations against Proteus vulgaris.
The pharmacokinetics and antibacterial efficacy of mezlocillin, cefotaxime, cefoperazone and the mezlocillin/cefalosporin combinations, respectively, were studied by adopting the granuloma pouch model in rats. Exudate concentrations of mezlocillin were higher after combined i.v. injection with a cefalosporin as determined microbiologically and by high performance liquid chromatography (HPLC). Cefoperazone levels, however, were not affected. Not metabolized cefotaxime concentrations as determined by HPLC were also not increased following simultaneous injection with mezlocillin. Cefotaxime metabolite concentrations, however, were generally higher than unchanged cefotaxime and increased upon repeated administration of cefotaxime alone and to a greater extent when combined with mezlocillin. Antibacterial efficacy of mono- or combined chemotherapy was correlated to beta-lactamase inducibility of the test strains insofar as drugs acting as good or moderate enzyme inducers were ineffective in vivo. The combined therapy of mezlocillin with cefotaxime was effective in this case. This result was also correlated to the bioavailability of the beta-lactams in infected pouches. Due to the degree of beta-lactamase inducibility and production, drug levels were either decreased or not detectable.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001682:Biological Availability; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004790:Enzyme Induction / Q000187:drug effects; D005122:Exudates and Transudates / Q000382:microbiology*; D005260:Female; D007700:Kinetics; D011512:Proteus Infections / Q000188:drug therapy / Q000201:enzymology*; D011514:Proteus vulgaris; D051381:Rats; D011919:Rats, Inbred Strains; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases