Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus  S. Croes, P.S. Beisser, P.H. Terporten, C. Neef, R.H. Deurenberg, E.E. Stobberingh  Clinical Microbiology and Infection  Volume 16, Issue 7, Pages 979-985 (July 2010) DOI: 10.1111/j.1469-0691.2010.02956.x Copyright © 2010 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 1 The pharmacodynamic effect, expressed as the difference in log viable count over a time period of 24 h, and denoted by the area between the curves (ABC0–24), vs. the concentration in mg/L for (a) oxacillin, (b) vancomycin and (c) daptomycin against borderline oxacillin-resistant Staphylococcus aureus strains M002, M007, M008, M015 and VU94 and methicillin-sensitive Staphylococcus aureus ATCC 29213. Clinical Microbiology and Infection 2010 16, 979-985DOI: (10.1111/j.1469-0691.2010.02956.x) Copyright © 2010 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 2 Antibacterial activity of oxacillin (OXA) against (a) Staphylococcus aureus ATCC 29213 (white symbols and dotted lines) vs. the average data for borderline oxacillin-resistant S. aureus (BORSA) strains M002, M008 and M015 (MICs of OXA ≥4 mg/L) (black symbols and straight lines) and (b) S. aureus ATCC 29213 (white symbols and dotted lines) vs. the average data for BORSA strains M007 and VU94 (MICs of OXA ≤2 mg/L) (black symbols and straight lines) at concentrations corresponding to 0.5× (circles), 1× (triangles downwards), 2× (squares), 4× (diamonds) and 8× MIC (triangles upwards) in comparison with growth controls (hexagon). Error bars represent standard errors of the mean. Clinical Microbiology and Infection 2010 16, 979-985DOI: (10.1111/j.1469-0691.2010.02956.x) Copyright © 2010 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 3 (a) The effect of β-lactamase induction by oxacillin on the nitrocefin-hydrolysing activities of borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains. (b) BORSA M007 and VU94 contain a BORSA-related, pBORa53-like plasmid. The image shows an ethidium bromidestained agarose gel containing HindIII-digested plasmids from M007 (lane 1), VU94 (lane 2), M002 (lane 3), M008 (lane 4) and M015 (lane 5). The fragment sizes of HindIII-digested DNA, as predicted from the sequences of the plasmids pBORa53 (GenBank Accession No. AY917098) and pMW2 (GenBank Accession No. AP004832), are indicated on the left- and right-hand side, respectively. Clinical Microbiology and Infection 2010 16, 979-985DOI: (10.1111/j.1469-0691.2010.02956.x) Copyright © 2010 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 4 The logarithm of (E/Emax-E) vs. the logarithm of the concentration in mg/L for Staphylococcus aureus ATCC 29213 (solid lines) and borderline oxacillin-resistant S. aureus (BORSA) M015 (dashed lines). The corresponding EC50 values were determined from the points where the dotted horizontal line (y = 0) intersects the different concentration–effect curves. The differences in potency are visualized by the left or right shift of the curves. The corresponding Hill coefficients (γ′) are equal to the slopes of the curves. The dotted vertical lines indicate the MIC of the represented antibiotics. The abbreviations DAP (a), OXA (c), LZD (b) and VAN (d) represent daptomycin, oxacillin, linezolid and vancomycin, respectively. Clinical Microbiology and Infection 2010 16, 979-985DOI: (10.1111/j.1469-0691.2010.02956.x) Copyright © 2010 European Society of Clinical Infectious Diseases Terms and Conditions