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Susceptibility

Daptomycin Bactericidal Activity and Correlation between Disk and Broth Microdilution Method Results in Testing of Staphylococcus aureus Strains with Decreased Susceptibility to Vancomycin

Helio S. Sader, Thomas R. Fritsche, Ronald N. Jones
Helio S. Sader
1JMI Laboratories, North Liberty, Iowa
2Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil
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  • For correspondence: helio-sader@jmilabs.com
Thomas R. Fritsche
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Ronald N. Jones
1JMI Laboratories, North Liberty, Iowa
3Tufts University School of Medicine, Boston, Massachusetts
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DOI: 10.1128/AAC.01491-05
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  • FIG. 1.
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    FIG. 1.

    Time-kill curve results for strain 170A tested against daptomycin (top) and vancomycin (bottom).

  • FIG. 2.
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    FIG. 2.

    Scattergram showing the correlation between the daptomycin broth microdilution MIC and disk zone diameter results.

  • FIG. 3.
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    FIG. 3.

    Scattergram showing the correlation between the vancomycin broth microdilution MIC and disk zone diameter results.

  • FIG. 4.
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    FIG. 4.

    Scattergram showing the correlation between the daptomycin broth microdilution and Etest MIC results.

Tables

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  • TABLE 1.

    MIC and MBC results for daptomycin and vancomycin

    Antimicrobial agent/organism (total no. of isolates)No. of isolates (cumulative %) at MIC/MBC (μg/ml) of:
    ≤0.120.250.5124816>16
    MIC
        Daptomycin
            MRSA-WT (102)a2 (2.0)41 (42.2) 56 b (97.1)3 (100.0)00000
            hVISA (88)02 (2.3) 52 (61.4)34 (100.0)00000
            VISA (17)002 (11.8) 7 (52.9) 7 (94.1)1 (100.0)000
        Vancomycin
            MRSA-WT (102)a−c−9 (8.8) 82 (89.2)11 (100.0)0000
            hVISA (88)−−0 (0.0)9 (10.2) 61 (79.5)18 (100.0)000
            VISA (17)−−0 (0.0)0 (0.0)0 (0.0) 11 (64.7)6 (100.0)00
    MBC
        Daptomycin
            MRSA-WT (102)a029 (28.4) 65 (92.2)7 (99.0)1 (100.0)0000
            hVISA (88)02 (2.3)35 (40.9) 49 (97.7)2 (100.0)0000
            VISA (17)002 (11.8)4 (35.3) 8 (82.4)3 (100.0)000
        Vancomycin
            MRSA-WT (102)a−−2 (2.0) 38 (39.2)23 (61.8)9 (70.6)15 (85.3)4 (89.2)11 (100.0)
            hVISA (88)−−03 (3.4)9 (14.9)5 (19.3)3 (22.7)7 (30.7) 61 (100.0)
            VISA (17)−−000000 17 (100.0)
    • ↵ a Clinical MRSA isolate with vancomycin MIC of ≤2 μg/ml (homogeneous populations) collected from medical centers worldwide in 2003.

    • ↵ b The underlined numbers are modal values.

    • ↵ c —, dilution not tested.

  • TABLE 2.

    Distribution of isolates according to MBC/MIC ratio for daptomycin and vancomycin

    MBC/MIC ratioNo. of isolates (%)
    DaptomycinVancomycin
    MRSA-WThVISAVISAMRSA-WThVISAVISA
    180 (78.4)69 (78.4)12 (70.6)42 (41.2)11 (12.5)
    222 (21.6)19 (21.6)5 (29.4)19 (18.6)5 (5.7)
    412 (11.8)4 (4.5)
    814 (13.7)7 (8.0)
    ≥1615 (14.7)a61 (69.3)a17 (100.0)a
    • ↵ a All isolates had vancomycin MBCs of >16 μg/ml.

  • TABLE 3.

    Time-kill curve results for vancomycin and daptomycin tested against bacteremic MRSA strains

    IsolateAntimicrobial agentReduction in log10 CFU/ml ata:Activity categoryb
    T4T8T24bT48
    170AVancomycin0.91.72.02.8Static
    Daptomycin4.85.66.3c−dCidal
    100AVancomycin0.51.11.92.1Static
    Daptomycin6.1c6.1c6.1c−Cidale
    13851AVancomycin0.71.12.94.3Statice
    Daptomycin4.86.1c6.1c−Cidal
    16546AVancomycin0.30.82.63.6Staticf
    Daptomycin3.54.85.7c−Cidalg
    14382AVancomycin0.10.41.73.0Static
    Daptomycin2.74.45.6c5.6cCidal
    2345AVancomycin0.51.02.43.4Statice
    Daptomycin4.06.0c6.0c6.0cCidal
    2308AVancomycin0.81.33.04.1Cidal
    Daptomycin4.26.0c6.0c−Cidal
    1416AVancomycin0.10.82.83.9Statice
    Daptomycin3.44.85.9c−Cidal
    2336AVancomycin0.40.93.25.6cCidal
    Daptomycin3.25.8c5.8c−Cidal
    16542AVancomycin0.31.03.85.5cCidal
    Daptomycin3.24.15.5c−Cidal
    16160AVancomycin0.51.73.64.2Cidal
    Daptomycin2.22.63.86.0cCidal
    5642AVancomycin0.50.72.43.7Statice
    Daptomycin2.64.04.3−Cidalg
    561AVancomycin0.30.82.03.6Statice
    Daptomycin3.65.7c5.7c−Cidal
    16325AVancomycin(0.1)h0.32.33.2Statice
    Daptomycin3.86.0c6.0c−Cidal
    456AVancomycin0.51.33.63.9Cidal
    Daptomycin4.55.6c5.6c−Cidal
    424AVancomycin0.41.03.53.5Cidal
    Daptomycin3.15.7c4.8−Cidal
    3811AVancomycin1.01.62.83.9Statice
    Daptomycin2.83.74.9−Cidal
    14854AVancomycin0.81.23.04.2Cidal
    Daptomycin4.45.26.0c−Cidal
    ATCC 29213Vancomycin1.21.42.74.6Statice
    Daptomycin3.25.9c5.9c5.9cCidal
    ATCC 43300Vancomycin0.71.02.83.7Staticf
    Daptomycin2.32.94.0−Cidalg
    ATCC 33591Vancomycin0.51.33.84.5Cidal
    Daptomycin4.04.85.7c−Cidal
    • ↵ a Compared to the initial inoculum. The values represent averages of 2×, 4×, and 8× reductions in log10 CFU/ml.

    • ↵ b Bactericidal (Cidal) activity was defined as ≥3 log10 reduction in the initial inoculum within 24 h of incubation.

    • ↵ c No bacterial growth was detected.

    • ↵ d −, incubated for 24 h only.

    • ↵ e Bactericidal activity was achieved only at 48 h of incubation.

    • ↵ f Bactericidal activity was achieved at 24 h when tested at 4× and/or 8× MIC.

    • ↵ g Bacteriostatic activity when tested at 2× MIC.

    • ↵ h Value in parentheses represents the increase in the log10 CFU/ml.

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Daptomycin Bactericidal Activity and Correlation between Disk and Broth Microdilution Method Results in Testing of Staphylococcus aureus Strains with Decreased Susceptibility to Vancomycin
Helio S. Sader, Thomas R. Fritsche, Ronald N. Jones
Antimicrobial Agents and Chemotherapy Jun 2006, 50 (7) 2330-2336; DOI: 10.1128/AAC.01491-05

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Daptomycin Bactericidal Activity and Correlation between Disk and Broth Microdilution Method Results in Testing of Staphylococcus aureus Strains with Decreased Susceptibility to Vancomycin
Helio S. Sader, Thomas R. Fritsche, Ronald N. Jones
Antimicrobial Agents and Chemotherapy Jun 2006, 50 (7) 2330-2336; DOI: 10.1128/AAC.01491-05
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KEYWORDS

Anti-Bacterial Agents
daptomycin
Staphylococcus aureus
vancomycin

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