Fig 1.
Flowchart of the materials and methods section.
Fig 2.
Total bacterial counts and baseline meropenem resistance in control growth experiments with OXA-48-producing K. pneumoniae.
Time courses of the total bacterial population indicated (black circles) and meropenem-resistant (2× (orange circles), 4× (red circles), 8× (purple circles), and 16×MIC (violet circles)) sub-populations of K. pneumoniae in growth control experiments.
Fig 3.
In vitro pharmacokinetics of meropenem without bacteria.
Targeted (line) and determined (red squares) concentrations of meropenem in in vitro pharmacokinetic experiments.
Fig 4.
In vitro pharmacokinetics of meropenem in the presence of bacteria.
Targeted (line) and determined (red squares) concentrations of meropenem in pharmacodynamic experiments with K. pneumoniae isolates. Mutant selection windows for each K. pneumoniae isolate are marked by shaded areas.
Fig 5.
Total bacterial counts and development of resistance in OXA-48-producing K. pneumoniae under the meropenem exposure (therapeutic regimen 2 grams every 8 hours as a 3-hours infusion).
Time courses of the total bacterial population (black circles) and meropenem-resistant (2× (orange circles), 4× (red circles), 8× (purple circles), and 16×MIC (violet circles)) sub-populations of K. pneumoniae in pharmacodynamic experiments.
Fig 6.
Relationship between the meropenem effectiveness and its total daily dose related to the K. pneumoniae MIC.
DOSE/MIC relationship with ABBC fitted by Eq (1): x0 = 2.34, a = 450, b = 0.32.
Table 1.
K. pneumoniae susceptibility to meropenem before and after antibiotic exposure in pharmacodynamic experiments.
Fig 7.
Relationship between the development of meropenem resistance (expressed as parameter ABBCR) in OXA-48-producing K. pneumoniae under antibiotic exposure and meropenem total daily dose related to MIC against the respective bacterial isolate.
DOSE/MIC relationship with ABBCR for mutants resistant to 4×MIC of meropenem; data fitted by Eq (2): x0 = 1.12, a = 645, b = 0.43.
Fig 8.
Relationship between the development of meropenem resistance (expressed as MICFIN/MICINIT ratio) in OXA-48-producing K. pneumoniae under antibiotic exposure and meropenem total daily dose related to MIC against the respective bacterial isolate.
DOSE/MIC relationships with MICFIN/MICINIT ratio; data fitted by Eq (3): Y0 = 1, x0 = 1.43, a = 78, b = 0.20.