title: Integration of selected pharmacologic and microbiologic properties of three new beta-lactam antibiotics: a hypothesis for rational comparison.
abstract: To enable the comparison of antibiotics in a standardized, meaningful manner, a system that integrates the pharmacologic and microbiologic properties of beta-lactam antibiotics has been developed. The system compares the duration of time that concentrations of both total and free drug exceed the 90% minimal inhibitory concentration ( MIC90 ) of various pathogens as well as the area under the concentration-time curve for both total and free drug, the latter measurement being an indication of potential for antibiotic diffusion to the periphery. Of the three cephalosporin(-like) compounds evaluated, moxalactam produced the longest duration of free drug above the MIC90 for the Enterobacteriaceae as well as the largest free-drug area under the concentration-time curve following a standardized 2-g intravenous infusion. Both the duration of time cefotaxime was above the MIC90 for the Enterobacteriaceae and the area under the concentration-time curve were significantly less because of its short elimination half-life, results indicating the need for more frequent dosing with cefotaxime than with moxalactam. Cefoperazone, because of its high degree of protein binding and higher MIC90 , develops the least duration of time above the MIC90 for most pathogens. None of these new agents provides free-drug concentrations above the MIC90 for Pseudomonas aeruginosa for longer than 0.6 hr, which suggests that they may be inadequate as single-agent therapy for many serious infections due to this pathogen. Because promotion of comparisons by this method relies on in vitro data for analysis, the conclusions relating to expected clinical efficacy are proffered and should be interpreted with caution.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy; D002438:Cefoperazone / Q000378:metabolism* / Q000494:pharmacology; D002439:Cefotaxime / Q000378:metabolism* / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009070:Moxalactam / Q000378:metabolism* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D018805:Sepsis / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D002438:Cefoperazone; D002439:Cefotaxime; D009070:Moxalactam