TABLE 2

Target versus observed pharmacodynamic parameters achieved in the in vitro pharmacodynamic modela

IsolateAmikacinCeftazidimeAvibactam
Target fAUC/MICObserved fAUC/MICTarget fT>MIC (%)Observed fT>MIC (%)Target fT>1 μg/ml (%)cCalculated fT>1 μg/ml (%)d
P. aeruginosa
    C42-724,4823,379 ± 40490.676.2 ± 22.3b75.893.9 ± 8.6
    C42-452,2411,909 ± 11190.696.7 ± 0.575.899.6 ± 0.8
    1504560425 ± 1710099.4 ± 0.875.899.5 ± 0.7
K. pneumoniae
    329b1,120881 ± 10100100.075.898.8 ± 2.2
    375560492 ± 310099.7 ± 0.375.899.8 ± 0.3
    352560465 ± 1090.696.3 ± 3.875.8100.0
  • a Observed pharmacodynamic exposure reported as mean ± standard deviation of results from two to four observations.

  • b One ceftazidime-avibactam experiment (when studied in combination with amikacin) resulted in less than the target ceftazidime fT>MIC due to low concentrations in one 8-h interval. The bacterial time-kill curve did not appear different from its duplicate run, and exposure was still above 50% fT>MIC and was observed only in the combination run, so this experiment was included.

  • c Target fT>1 μg/ml values for avibactam were derived from the ELF concentration profile (13).

  • d Avibactam concentrations were not measured in the experiment but were calculated as one-fourth of ceftazidime concentrations due to the use of a formulation with a 4:1 ceftazidime/avibactam concentration ratio. Note that the pharmacodynamic target exposure for avibactam is at least 50% fT>1 μg/ml, and therefore this exposure was achieved in all experiments.