Development of an optimized and practical pharmacokinetics/pharmacodynamics analysis method for aztreonam/nacubactam against carbapenemase-producing K. pneumoniae.
J Antimicrob Chemother
; 78(4): 991-999, 2023 04 03.
Article
en En
| MEDLINE
| ID: mdl-36775998
ABSTRACT
BACKGROUND:
Nacubactam, a new ß-lactamase inhibitor with antibacterial activity, is being developed as a single drug to be co-administered with cefepime or aztreonam. However, determining pharmacokinetics/pharmacodynamics (PK/PD) parameters in ß-lactam/ß-lactamase inhibitor combinations remains challenging. We aimed to establish a practical PK/PD analysis method for aztreonam/nacubactam that incorporates instantaneous MIC (MICi).METHODS:
Based on chequerboard MIC measurements, MICi of aztreonam against carbapenemase-producing Klebsiella pneumoniae in the presence of nacubactam was simulated.RESULTS:
The mean change in the bacterial count of thigh-infected mice in an in vivo PD study was plotted based on %fT>MICi and analysed using the inhibitory effect sigmoid Imax model. fT>MICi calculated from the PK experiments showed a high correlation with the in vivo bactericidal effect, suggesting that fT>MICi is the optimal PK/PD parameter for aztreonam/nacubactam. The target values of fT>MICi achieving growth inhibition, 1 log10 kill and 2 log10 kill, were 22, 38% and 75%, respectively.CONCLUSIONS:
The PK/PD analysis method proposed in this study is promising for determining practical PK/PD parameters in combination therapy. In addition, this is the first report of aztreonam/nacubactam showing a potent in vivo therapeutic effect against NDM-producing K. pneumoniae.
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Aztreonam
/
Inhibidores de beta-Lactamasas
Límite:
Animals
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón