Linked Life Data

20368392

Source:http://linkedlifedata.com/resource/pubmed/id/20368392

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-18
pubmed:abstractText
The objective of this study was to implement a semimechanistic pharmacokinetic-pharmacodynamic (PK-PD) model to describe the effects of ciprofloxacin against Pseudomonas aeruginosa in vitro. Time-kill curves were generated with an initial inoculum close to 5 x 10(6)CFU/ml of P. aeruginosa PAO1 and constant ciprofloxacin concentrations between 0.12 and 4.0 microg/ml (corresponding to 0.5x and 16x MIC). To support the model, phenotypic experiments were conducted with the PAO7H mutant strain, which overexpresses the MexEF OprN efflux pump and phenyl arginine beta-naphthylamide (PAbetaN), a known efflux inhibitor of main Mex multidrug efflux systems. A population approach was used for parameter estimation. At subinhibitory ciprofloxacin concentrations (0.12 and 0.25 microg/ml), an initial CFU decay followed by regrowth was observed, attesting to rapid emergence of bacteria with increased but moderate resistance (8-fold increase of MIC). This phenomenon was mainly due to an overexpression of the Mex protein efflux pumps, as shown by a 16-fold diminution of the MIC in the presence of PAbetaN in these strains with low-level resistance. A PK-PD model with adaptation development was successfully used to describe these data. However, additional experiments are required to validate the robustness of this model after longer exposure periods and multiple dosing regimens, as well as in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-6596
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2379-84
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Semimechanistic pharmacokinetic-pharmacodynamic model with adaptation development for time-kill experiments of ciprofloxacin against Pseudomonas aeruginosa.
pubmed:affiliation
Université de Poitiers, CHU Poitiers, INSERM Eri-23, Poitiers, France2 France.
pubmed:publicationType
Journal Article, In Vitro