Table 1.
Primers used for PCR reactions to amplify the relevant regions of the indicated genes.
Fig 1.
Comparison of the computer-simulated 5, 50, and 95 percentile concentrations of ceftazidime and meropenem as a function of time in critically ill patients and the concentrations achieved in the chemostat.
Fig 2.
Density of a culture of P. aeruginosa exposed to ceftazidime and meropenem in the chemostat (D = 0.3 h-1) at concentrations simulating the 5, 50 and 95 percentile of the concentration-time profiles as they are expected in critically ill patients.
Cultures were in steady state in the absence of antibiotics before day 0.
Fig 3.
Comparison of cell morphology of regular growing culture and a culture growing at the 50 percentile concentration of ceftazidime during the initial exposure.
Exposure to other concentrations of ceftazidime and all experimental concentrations of meropenem yielded a similar morphology.
Fig 4.
Minimum inhibitory concentrations (MIC) of P. aeruginosa culture as a function of time (days) during exposure to the 5, 50, and 95 percentile of concentration-time profiles as they are to be expected in critically ill patients of ceftazidime (left panel) and meropenem (right panel) in chemostats (D = 0.3 h-1).
Fig 5.
Fraction of cells from chemostat cultures that can grow on plates containing the 5, 50, 95 percentile of the ceftazidime steady-state concentration and the meropenem trough concentration (8 hour after drug administration) as these are to be expected in critically ill patients, as a function of time (days) during growth at the indicated antibiotic levels.
Fig 6.
Maximum growth rate (μmax) in the absence of antibiotics of cells taken from chemostat cultures exposed to the 95 percentile of concentration-time profiles as they are to be expected in critically ill patients of ceftazidime or meropenem as a function of time (days).
For each time point, the growth rate of four independent samples was measured.
Table 2.
Mutations detected in P. aeruginosa cultures during exposure to the 5, 50, and 95 percentile of concentration-time profiles as they are to be expected in critically ill patients of ceftazidime (ampD, dacB, hfq, yerD) and meropenem (oprD, mexR, mexB).