Mechanism-Based Disease Progression Model Describing Host-Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia.
CPT Pharmacometrics Syst Pharmacol
; 7(8): 507-516, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29761668
ABSTRACT
The emergence of highly resistant bacteria is a serious threat to global public health. The host immune response is vital for clearing bacteria from the infected host; however, the current drug development paradigm does not take host-pathogen interactions into consideration. Here, we used a systems-based approach to develop a quantitative, mechanism-based disease progression model to describe bacterial dynamics, host immune response, and lung injury in an immunocompetent rat pneumonia model. Previously, Long-Evans rats were infected with Acinetobacter baumannii (A. baumannii) strain 307-0294 at five different inocula and total lung bacteria, interleukin-1beta (IL-1ß), tumor necrosis factor-α (TNF-α), cytokine-induced neutrophil chemoattractant 1 (CINC-1), neutrophil counts, and albumin were quantified. Model development was conducted in ADAPT5 version 5.0.54 using a pooled approach with maximum likelihood estimation; all data were co-modeled. The final model characterized host-pathogen interactions during the natural time course of bacterial pneumonia. Parameters were estimated with good precision. Our expandable model will integrate drug effects to aid in the design of optimized antibiotic regimens.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Bacteriana
/
Acinetobacter baumannii
/
Interações Hospedeiro-Patógeno
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos