title: Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods.
abstract: Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and β-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 μg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any β-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 μg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Cheng Len
authors.initials: CL
authors.lastname: Sy
authors.affiliation: Division of Microbiology, Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Tsi-Shu
authors.initials: TS
authors.lastname: Huang
authors.affiliation: Division of Microbiology, Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chii Shiang
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yao-Shen
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hung-Chin
authors.initials: HC
authors.lastname: Tsai
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Shue-Renn
authors.initials: SR
authors.lastname: Wann
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuan-Sheng
authors.initials: KS
authors.lastname: Wu
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Jui-Kuang
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan ssjlee28@yahoo.com.tw.
authors.forename: Susan Shin-Jung
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, Shuang-Ho Hospital, Taipei, Taiwan Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Ching
authors.initials: YC
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D014640:Vancomycin / Q000494:pharmacology*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D014640:Vancomycin