Impact of the antibiotic dosage schedule on efficacy in experimental soft tissue infections. 1990

A U Gerber
Division of Medicine, Regionalspital Burgdorf, Switzerland.

Soft tissue infection models have been used to study both the postantibiotic effect (PAE) and the effect of dosage intervals on antimicrobial efficacy. In vitro findings were mostly confirmed. For drug-organism combinations which showed a predominantly time-dependent killing pattern and absence of a PAE (beta-lactams vs Gram-negative organisms), frequent drug dosing was most efficacious. In contrast, a fast, predominantly concentration-dependent bactericidal effect followed by a PAE in vitro (e.g. aminoglycosides vs Gram-negative bacteria) correlated (though inconsistently) with superiority of bolus dosing over more continuous drug administration in vivo. Thus, the ratio of peak serum concentrations to MICs of target pathogens is possibly a valid predictor of efficacy for the aminoglycosides but not so for the activity of beta-lactam antibiotics where the duration of coverage at supra-MIC levels was clearly more important than the magnitude by which initial peaks exceeded the MIC of the target organism. It is not clear to what extent the results obtained in experimental soft tissue infections may hold true in man. Thus far, only a limited number of drug-organism combinations have been studied in well defined experimental settings using mostly small, granulocytopenic animals which differ pharmacokinetically from man. In addition, results are probably affected by the density of bacteria, their growth rate and metabolic activity, but also by the extent of inflammation at the site of infection.

UI MeSH Term Description Entries
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001424 Bacterial Infections Infections by bacteria, general or unspecified. Bacterial Disease,Bacterial Infection,Infection, Bacterial,Infections, Bacterial,Bacterial Diseases

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