title: Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus.
abstract: Since it is unknown whether β-lactam antimicrobial agents can be used effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) with oxacillin MICs ≥4 mg/L, the in vitro bactericidal activity and pharmacodynamic effect of oxacillin against clinical BORSA isolates was evaluated. Time-kill experiments with oxacillin were performed and the results compared with those obtained with vancomycin, daptomycin and linezolid against BORSA with oxacillin MICs ≥4 mg/L and BORSA with oxacillin MICs ≤2 mg/L. Furthermore, the effect of β-lactamase production and plasmid profile analysis were taken into account to clarify responses to oxacillin. Oxacillin killing activity was attenuated against BORSA compared with ATCC 29213 since the pharmacodynamic parameters revealed that the potency of oxacillin was markedly reduced (c. ten-fold) against BORSA with oxacillin MICs ≥4 mg/L. pBORa53-like plasmid-containing BORSA with oxacillin MICs ≤2 mg/L showed markedly more regrowth. In conclusion, oxacillin was non-effective in the eradication of either (i) BORSA with oxacillin MICs ≥4 mg/L or (ii) β-lactamase-hyperproducing BORSA (MICs ≤2 mg/L). Further investigation into β-lactam dosing strategies against different BORSA strains is warranted in order to avoid possible therapy failure.
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Croes
authors.forename: P S
authors.initials: PS
authors.lastname: Beisser
authors.forename: P H
authors.initials: PH
authors.lastname: Terporten
authors.forename: C
authors.initials: C
authors.lastname: Neef
authors.forename: R H
authors.initials: RH
authors.lastname: Deurenberg
authors.forename: E E
authors.initials: EE
authors.lastname: Stobberingh
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D017576:Daptomycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010957:Plasmids / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D023303:Oxazolidinones; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus; D014640:Vancomycin; D001618:beta-Lactamases; D000069349:Linezolid; D017576:Daptomycin; D010068:Oxacillin