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Susceptibility

Antipneumococcal Activities of GAR-936 (a New Glycylcycline) Compared to Those of Nine Other Agents against Penicillin-Susceptible and -Resistant Pneumococci

Dianne B. Hoellman, Glenn A. Pankuch, Michael R. Jacobs, Peter C. Appelbaum
Dianne B. Hoellman
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,and
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Glenn A. Pankuch
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,and
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Michael R. Jacobs
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106
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Peter C. Appelbaum
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,and
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DOI: 10.1128/AAC.44.4.1085-1088.2000
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    Fig. 1.

    Graphical depiction of GAR-936 kill kinetics versus a tetracycline-resistant (MIC, 64.0 μg/ml) strain of S. pneumoniae.

Tables

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  • Table 1.

    Agar dilution MICs for 201 pneumococcal isolates

    DrugPenicillin susceptibility of strainaMIC (μg/ml)
    RangeMIC50bMIC90c
    PenicillinS≤0.008–0.06≤0.0160.03
    I0.125–1.00.251.0
    R2.0–>8.02.04.0
    GAR-936S≤0.016–0.1250.030.125
    I≤0.016–0.1250.030.06
    R≤0.016–0.1250.060.125
    TetracyclineS≤0.06–64.00.2532.0
    I≤0.06–64.01.064.0
    R≤0.25–128.032.064.0
    MinocyclineS≤0.06–16.00.068.0
    I≤0.06–16.00.2516.0
    R≤0.06–16.04.016.0
    DoxycyclineS0.03–16.00.1258.0
    I≤0.06–32.00.58.0
    R0.125–16.04.08.0
    AmoxicillinS≤0.008–0.250.0160.03
    I≤0.016–2.00.1251.0
    R0.5–4.02.02.0
    CeftriaxoneS≤0.008–1.00.0160.03
    I≤0.016–2.00.251.0
    R0.25–8.01.02.0
    ClarithromycinS≤0.016–>128.00.038.0
    I≤0.016–>128.00.06>128.0
    R≤0.016–>128.01.0>128.0
    ImipenemS≤0.008–0.25≤0.0080.016
    I≤0.008–0.250.060.25
    R0.03–0.50.250.5
    MeropenemS≤0.008–0.50.0160.03
    I≤0.016–0.50.1250.5
    R0.125–2.00.51.0
    VancomycinS≤0.06–0.50.250.25
    I≤0.06–0.50.250.25
    R0.125–0.50.250.25
    • ↵a S, penicillin susceptible; I, penicillin intermediate; R, penicillin resistant.

    • ↵b MIC50, MIC at which 50% of the isolates tested were inhibited.

    • ↵c MIC90, MIC at which 90% of the isolates tested were inhibited.

  • Table 2.

    Microbroth MICs for 12 strains tested by the time-kill method

    DrugMIC (μg/ml) for straina:
    1(S)2(S)3(S)4(S)5(I)6(I)7(I)8(I)9(R)10(R)11(R)12(R)
    Penicillin0.060.0160.030.030.50.50.250.254.02.04.04.0
    GAR-9360.060.030.030.060.1250.060.030.030.030.030.060.06
    Tetracycline64.00.564.00.54.064.00.1250.2532.032.01.032.0
    Minocycline16.00.1258.00.1250.564.00.060.0616.08.00.254.0
    Doxycycline8.00.2516.00.251.016.00.060.1258.08.01.08.0
    Amoxicillin0.030.030.0160.0160.060.1250.1250.061.01.02.02.0
    Ceftriaxone0.060.0160.0160.0160.1251.00.060.062.02.01.02.0
    Clarithromycin>64.00.030.0160.03>64.00.0080.0160.03>64.0>64.00.03>64.0
    Imipenem0.0080.0080.0080.0080.030.060.030.030.250.250.50.25
    Meropenem0.0160.0160.0160.0080.060.1250.1250.061.00.51.01.0
    Vancomycin0.250.250.50.50.250.50.50.1250.50.250.250.25
    • ↵a S, penicillin susceptible; I, penicillin intermediate; R, penicillin resistant.

  • Table 3.

    Results of time-kill assays of 12 pneumococcal strains

    Drug and concnNo. of strains killed by time point, with Δlog10 CFU/ml (from time zero value) of:
    3 h6 h12 h24 h
    −1−2−3−1−2−3−1−2−3−1−2−3
    GAR-936
     8× MIC731126412117121212
     4× MIC621126412106121211
     2× MIC52111531296121111
     MIC4117521084121111
     0.5× MIC000300321532
    Tetracyclinea
     8× MIC310533543665
     4× MIC200430542665
     2× MIC200320522655
     MIC100200320331
     0.5× MIC000000100000
    Minocyclinea
     8× MIC421442544655
     4× MIC311432543655
     2× MIC210422543654
     MIC200320532643
     0.5× MIC100100000000
    Doxycyclinea
     8× MIC420533553655
     4× MIC310530553655
     2× MIC100410541654
     MIC100210211222
     0.5× MIC000100100000
    Amoxicillin
     8× MIC104012106121210121212
     4× MIC920119312128121212
     2× MIC830118212127121212
     MIC520114210531088
     0.5× MIC100210110211
    Ceftriaxone
     8× MIC80012100121210121212
     4× MIC810129112118121212
     2× MIC800107012108121212
     MIC510960107110108
     0.5× MIC200200110000
    Clarithromycinb
     8× MIC420740744776
     4× MIC310630744766
     2× MIC310431744766
     MIC210420643764
     0.5× MIC100200210211
    Imipenem
     8× MIC124012102121110121212
     4× MIC11501292121110121212
     2× MIC11301294121110121212
     MIC102012821210811119
     0.5× MIC800630420332
    Meropenem
     8× MIC1131125212129121212
     4× MIC920124212127121211
     2× MIC640127312118121211
     MIC621115211951098
     0.5× MIC100200100211
    Vancomycin
     8× MIC710126112119121212
     4× MIC710126212109121211
     2× MIC710126212108121211
     MIC610124011951097
     0.5× MIC000200200220
    • ↵a Only strains with tetracycline MICs of <8.0 μg/ml were tested.

    • ↵b Only strains with clarithromycin MICs of <4.0 μg/ml were tested.

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Antipneumococcal Activities of GAR-936 (a New Glycylcycline) Compared to Those of Nine Other Agents against Penicillin-Susceptible and -Resistant Pneumococci
Dianne B. Hoellman, Glenn A. Pankuch, Michael R. Jacobs, Peter C. Appelbaum
Antimicrobial Agents and Chemotherapy Apr 2000, 44 (4) 1085-1088; DOI: 10.1128/AAC.44.4.1085-1088.2000

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Antipneumococcal Activities of GAR-936 (a New Glycylcycline) Compared to Those of Nine Other Agents against Penicillin-Susceptible and -Resistant Pneumococci
Dianne B. Hoellman, Glenn A. Pankuch, Michael R. Jacobs, Peter C. Appelbaum
Antimicrobial Agents and Chemotherapy Apr 2000, 44 (4) 1085-1088; DOI: 10.1128/AAC.44.4.1085-1088.2000
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KEYWORDS

Anti-Bacterial Agents
minocycline
Streptococcus pneumoniae

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