TABLE 6

MICs for mutants of aztreonam-susceptible (i.e., ESBL- and AmpC-negative) MBL producers

StrainaMIC (μg/ml) for drug alone or in combinationb
OP0595Piperacillin + OP0595Cefepime + OP0595Aztreonam + OP0595Meropenem + OP0595Ceftazidime
0248024801240248Alone+AVI
E. coli H112760544 (VIM)
    Parent1>256≤0.016≤0.016≤0.01664≤0.016≤0.016≤0.0160.125≤0.016≤0.016≤0.0168≤0.016≤0.016≤0.016>256256
    Mut 1>32>256646464128161680.125≤0.016≤0.016≤0.01640.2521>256256
    Mut 2>32>25664643264161680.1250.030.030.034121>256128
    Mut 3>32>256444162220.03≤0.016≤0.016≤0.01610.250.250.12512832
    Mut 4>32>256643232168440.03≤0.016≤0.016≤0.01610.50.50.56432
    Mut 58>2560.060.030.03128≤0.016≤0.016≤0.0160.125≤0.016≤0.016≤0.01616≤0.016≤0.016≤0.016>256128
E. coli H112760545 (VIM)
    Parent1>256≤0.016≤0.016≤0.01664≤0.016≤0.016≤0.0160.125≤0.016≤0.016≤0.0168≤0.016≤0.016≤0.016>256256
    Mut 1>32>256323232164440.03≤0.016≤0.016≤0.01610.250.1250.125256128
    Mut 2>32>256824642220.125≤0.016≤0.016≤0.01620.125≤0.016≤0.01625632
    Mut 332>2561620.1251280.50.250.030.125≤0.016≤0.016≤0.0164≤0.016≤0.016≤0.016>256128
    Mut 4>32>256323232164440.03≤0.016≤0.016≤0.01610.250.250.2512864
    Mut 5>32>2566464641281616160.1250.030.030.034222>256256
Klebsiella H090380495 (IMP)
    Parent164≤0.016≤0.016≤0.01632≤0.016≤0.016≤0.0160.125≤0.016≤0.016≤0.01616≤0.016≤0.016≤0.016>2560.25
    Mut 1>32320.50.50.5161210.25≤0.016≤0.016≤0.01640.125≤0.016≤0.016>25616
    Mut 2>32640.50.250.25642220.250.030.030.034444>25616
    Mut 3>3232222328880.250.030.030.038444>256128
    Mut 4>321611182220.1250.030.030.032222>25632
    Mut 5>32160.50.50.5642210.125<0.016<0.016<0.0168222>25616
Citrobacter H124560395 (NDM)
    Parent4>25664≤0.016≤0.016648≤0.016≤0.0160.250.125≤0.016≤0.016162≤0.016≤0.016>256>256
    Mut 1>3212816161684440.03≤0.016≤0.016≤0.0162222>256>256
    Mut 2>32128323232328880.1250.060.030.034444>256>256
    Mut 3>32>25664646432161680.1250.06≤0.016≤0.01616163216>256>256
    Mut 4>32128323232168880.1250.030.030.034444>256>256
    Mut 5>32256323232328840.06≤0.016≤0.016≤0.0164444>256>256
Klebsiella H101620268 (IMP)
    Parent232≤0.016≤0.016≤0.01616≤0.016≤0.016≤0.0160.03≤0.016≤0.016≤0.0168≤0.016≤0.016≤0.016256256
    Mut 1>3280.50.50.5810.250.250.03≤0.016≤0.016≤0.01610.510.5642
    Mut 2>321610.50.5162220.03≤0.016≤0.016≤0.016884412832
    Mut 3>323210.50.5164440.060.030.030.03884425664
    Mut 4>3280.50.50.2584440.03≤0.016≤0.016≤0.01684446416
    Mut 5>3232221321616160.060.030.030.031616161625664
Citrobacter H132820363 (NDM)
    Parent1>256≤0.016≤0.016≤0.01632≤0.016≤0.016≤0.0160.06≤0.016≤0.016≤0.0164≤0.016≤0.016≤0.016>256>256
    Mut 1>32>2561680.5324440.125≤0.016≤0.016≤0.0164222>256>256
    Mut 2>32>2566464323216880.1250.030.030.038888>256>256
    Mut 4>32256161616164440.1250.030.030.034444>256>256
    Mut 5>32>2561680.5644440.125≤0.016≤0.016≤0.0164222>256>256
  • a The strain (e.g., E. coli H112760544) and the metallocarbapenemase it possesses (IMP, NDM, or VIM) are shown. The parent strain and the five mutants (Mut 1 to Mut 5) studied here are given.

  • b The MICs of drugs alone or in combination with the OP0595 diazabicyclooctane at 2, 4, and 8 µg/ml (0 for no OP0595) are shown. All MICs are shown in micrograms per milliliter. The MIC of ceftazidime alone and with avibactam (+AVI) (4 μg/ml) is shown for comparison.