title: [PK/PD Modeling as a Tool for Predicting Bacterial Resistance to Antibiotics: Alternative Analyses of Experimental Data].
abstract: Postexposure number of mutants (NM) is a conventional endpoint in bacterial resistance studies using in vitro dynamic models that simulate antibiotic pharmacokinetics. To compare NM with a recently introduced integral parameter AUBC(M), the area under the time course of resistance mutants, the enrichment of resistant Staphylococcus aureus was studied in vitro by simulation of mono(daptomycin, doxycycline) and combined treatments (daptomycin + rifampicin, rifampicin + linezolid). Differences in the time courses of resistant S. aureus could be reflected by AUBC(M) but not N(M). Moreover, unlike AUBC(M), N(M) did not reflect the pronounced differences in the time courses of S. aureus mutants resistant to 2x, 4x, 8x and 16xMIC of doxycycline and rifampicin. The findings suggested that AUBC(M) was a more appropriate endpoint of the amplification of resistant mutants than N(M).
authors.forename: M V
authors.initials: MV
authors.lastname: Golikova
authors.forename: E N
authors.initials: EN
authors.lastname: Strukova
authors.forename: Y A
authors.initials: YA
authors.lastname: Portnoy
authors.forename: A A
authors.initials: AA
authors.lastname: Firsov
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents