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Susceptibility

Antistaphylococcal Activity of CB-181963 (CAB-175), an Experimental Parenteral Cephalosporin

Dianne B. Hoellman, Glenn A. Pankuch, Peter C. Appelbaum
Dianne B. Hoellman
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania
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Glenn A. Pankuch
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania
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Peter C. Appelbaum
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania
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  • For correspondence: pappelbaum@psu.edu
DOI: 10.1128/AAC.48.10.4037-4039.2004
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    FIG. 1.

    CB-181963 chemical structure.

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  • TABLE 1.

    MICs (in micrograms per milliliter) for 265 S. aureus strains

    DrugMethicillin susceptible (n = 66)Methicillin resistant (n = 199)
    RangeMIC50MIC90RangeMIC50MIC90
    CB-181963≤0.12-10.510.5-424
    Vancomycin0.5-4120.5-25612
    Teicoplanin0.25-1612≤0.12-1280.51
    Linezolid≤0.25-2220.5-222
    Ranbezolid≤0.25-4240.5-824
    Tigecycline≤0.06-10.250.5≤0.06-10.250.25
    Quinupristin- dalfopristin0.12-10.250.5≤0.06-10.50.5
    Levofloxacin0.12->328320.12->328>32
  • TABLE 2.

    MICs of available compounds active against VISA and VRSA strains

    DrugMIC (μg/ml) for straina:
    NRS1NRS12NRS17NRS56NRS63VRS1VRS2
    CB-1819634142144
    Linezolid1220.5211
    Quinupristin-dalfopristin0.50.250.50.50.250.250.25
    Daptomycinb2.02.02.02.01.00.50.25
    • ↵ a NARSA repository numbers are used for strain designations.

    • ↵ b Values for daptomycin are from reference 2 and unpublished results.

  • TABLE 3.

    MICs for six S. aureus strains tested by time kill

    DrugMIC (μg/ml) for strain no:
    1a2a3a4a5b6c
    CB-1819632.02.04.02.04.02.0
    Vancomycin1.01.01.01.04.032
    Teicoplanin0.51.00.251.04.08.0
    Linezolid2.04.04.04.01.04.0
    Ranbezolid2.04.04.02.01.02.0
    Tigecycline0.250.250.50.250.250.125
    Quinupristin-dalfopristin0.50.50.50.50.50.5
    Levofloxacin32641681632
    • ↵ a Methicillin resistant.

    • ↵ b Vancomycin intermediate.

    • ↵ c Vancomycin resistant.

  • TABLE 4.

    Time-kill results of six S. aureus strains

    Drug and concnNo. of strains killed at time pointa:
    3 h6 h12 h24 h
    −1−2−3−1−2−3−1−2−3−1−2−3
    CB-181963
        4× MIC000610654666
        2× MIC000510653665
        MIC000510643222
    Vancomycin
        4× MIC100210621663
        2× MIC100200621653
        MIC000200610542
    Teicoplanin
        4× MIC100410641642
        2× MIC100310641631
        MIC100210631421
    Linezolid
        4× MIC000000000300
        2× MIC000000000300
        MIC000000000000
    Ranbezolid
        4× MIC000000100200
        2× MIC000000100100
        MIC000000000000
    Tigecycline
        4× MIC000000000200
        2× MIC000000000100
        MIC000000000100
    Quinupristin- dalfopristin
        4× MIC000100100610
        2× MIC000100100310
        MIC000100100210
    Levofloxacin
        4× MIC100440643654
        2× MIC100430643653
        MIC100330643641
    • ↵ a −1, 90% killing; −2, 99% killing; −3, 99.9% killing.

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Antistaphylococcal Activity of CB-181963 (CAB-175), an Experimental Parenteral Cephalosporin
Dianne B. Hoellman, Glenn A. Pankuch, Peter C. Appelbaum
Antimicrobial Agents and Chemotherapy Sep 2004, 48 (10) 4037-4039; DOI: 10.1128/AAC.48.10.4037-4039.2004

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Antistaphylococcal Activity of CB-181963 (CAB-175), an Experimental Parenteral Cephalosporin
Dianne B. Hoellman, Glenn A. Pankuch, Peter C. Appelbaum
Antimicrobial Agents and Chemotherapy Sep 2004, 48 (10) 4037-4039; DOI: 10.1128/AAC.48.10.4037-4039.2004
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KEYWORDS

cephalosporins
Staphylococcus aureus

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