TABLE 1

IC50s of β-lactams for S. pneumoniae IU1945

β-Lactam class and drugMIC (μg/ml)IC50 (μg/ml)aPBP selectivity
PBP1aPBP1bPBP2xPBP2aPBP2bPBP3
Monobactams
    Aztreonam64NDND67 ± 1100 ± 1>1,0000.051 ± 0.0033c
Penems
    Faropenem0.0160.0024 ± 0.00020.011 ± 0.0010.007* ± 0.0020.0089* ± 0.00040.0038* ± 0.00050.0035* ± 0.0008NSe
Carbapenems
    Doripenem0.0080.0085* ± 0.00130.035 ± 0.0180.0082* ± 0.00090.082 ± 0.0410.029 ± 0.0110.0042 ± 0.00011a, 2x, 3
    Meropenem0.0160.0054* ± 0.00060.059 ± 0.0120.011* ± 0.0021.6 ± 0.80.027 ± 0.0010.0031 ± 0.00051a, 2x, 3
Penicillins
    Penicillin V0.0080.022 ± 0.0010.036 ± 0.0050.0074* ± 0.00090.14 ± 0.030.15 ± 0.050.0046 ± 0.00032x, 3
    Penicillin G0.0080.020 ± 0.0010.028 ± 0.0020.0059* ± 0.00000.038 ± 0.0020.13 ± 0.010.0024 ± 0.00012x, 3
    Ampicillin0.0160.077* ± 0.0310.24 ± 0.110.046* ± 0.031b0.14 ± 0.09b0.12 ± 0.050.022 ± 0.013b1a, 2x, 3d
    Amoxicillin0.0160.069 ± 0.0290.17 ± 0.12b0.025* ± 0.0140.12 ± 0.050.078 ± 0.0270.012 ± 0.0052x, 3
    Oxacillin0.0161.5 ± 0.31.3 ± 0.20.038 ± 0.0133.7 ± 0.61.4 ± 0.30.071* ± 0.0062x, 3
    Piperacillin0.0164.8 ± 4.0b4.1 ± 3.5b0.020 ± 0.0080.94 ± 0.070.18 ± 0.11b0.056* ± 0.0002x, 3d
    Methicillin0.1259.9 ± 0.44.9 ± 0.50.083 ± 0.0124.3 ± 0.92.5 ± 0.40.16* ± 0.002x, 3
    Amdinocillin473* ± 248 ± 4>1,000>1,000>1,000>1,0001a, 1b
    6-APA64>1,000>1,000>1,000>1,000>1,000>1,000NS
Cephalosporins
    Ceftriaxone0.0080.15 ± 0.050.064 ± 0.0060.012* ± 0.0020.21 ± 0.03>1,0000.011 ± 0.009b2x, 3d
    Cefuroxime0.0160.22 ± 0.010.10 ± 0.020.0031 ± 0.00070.053 ± 0.00564 ± 50.020 ± 0.0002x
    Cefotaxime0.0160.33 ± 0.010.22 ± 0.010.0078* ± 0.00020.17 ± 0.00>1,0000.0031 ± 0.00012x, 3
    Cephalothin0.250.018* ± 0.0100.013* ± 0.0050.043 ± 0.0050.13 ± 0.021.9 ± 0.20.0060 ± 0.00021a, 1b, 3
    Cefoxitin0.50.77 ± 0.360.14 ± 0.040.81 ± 0.240.42 ± 0.071.6 ± 0.50.0020 ± 0.00053
    Cephalexin1>1,000>1,0000.67 ± 0.06>1,00045 ± 20.035 ± 0.0013
    Cefsulodin416 ± 42.4 ± 0.21.7 ± 0.64.3 ± 0.7>1,0000.33 ± 0.173
  • a IC50s were generated as described in Materials and Methods using a log(inhibitor)-versus-response-variable slope (four parameters) and least square (ordinary) fit with GraphPad Prism software. Data from two experiments with the standard error are provided. An IC50 of >1,000 was assigned when GraphPad Prism reported an ambiguous number and significant inhibition was not seen at 1,000 μg/ml. Underlining indicates the lowest IC50 for each compound. Asterisks indicate IC50s within 4-fold of the lowest value. ND, not determined (GraphPad Prism reported an ambiguous number and/or an extremely wide confidence interval for IC50 determination [>106] for both data sets).

  • b IC50s obtained from duplicate data sets are ≥4-fold different.

  • c Selectivity assignment was possible due to apparent IC50s of PBP1a and PBP1b (≥4-fold above that of PBP3).

  • d Selectivity assignment is an estimate due to a high standard error value(s) in IC50 determination.

  • e NS, not selective.