Quantifying the Impact of Bacterial Fitness and Repeated Antimicrobial Exposure on the Emergence of Multidrug-Resistant Gram-Negative Bacilli

D'Agata, E. M.C., Horn, M., and Webb, G.. "Quantifying the Impact of Bacterial Fitness and Repeated Antimicrobial Exposure on the Emergence of Multidrug-Resistant Gram-Negative Bacilli." Mathematical Modelling of Natural Phenomena 2.1 (2010): 129-142. <http://eudml.org/doc/222298>.

@article{DAgata2010,
abstract = { The emergence of multidrug resistance among gram-negative bacilli is complex. Numerous factors need to be considered, including the biological fitness cost of resistance, fitnesscompensatory mutations and frequency and type of antibiotic exposure. A mathematical model evaluating these complex relationships was developed in an individual colonized with strains of pan-susceptible, single-, two- and multidrug-resistant (MDR) gram-negative bacilli (GN). The effect of bacterial fitness, compensatory mutations and the frequency of three-antimicrobial regimen exposure to predominance of multidrug-resistant strains were quantified. The model predicts that initially, in the absence of antibiotic exposure, the biologically fitter pan-susceptible strain predominates over the resistant strains. Over time, the fitness of the MDR strains increases faster with repeated antimicrobial exposure, through compensatory-fitness mutations. Increasing the frequency of exposure to the three-antimicrobial regimen or, increasing the initial fitness of the resistant strains, substantially decreases the time to MDR-GN predominance. The model implies that when MDR-GN strains evolve into strains that are fitter than susceptible strains, a reduction in antimicrobial exposure may not result in a decrease of MDR-GN, since the absence of selective antimicrobial pressure would no longer favor susceptible strains. The model also implies that antimicrobial cycling may promote the emergence of MDR-GN. },
author = {D'Agata, E. M.C., Horn, M., Webb, G.},
journal = {Mathematical Modelling of Natural Phenomena},
keywords = {multidrug-resistance; gram-negative bacteria; antibiotic resistance; mathematical modeling; bacterial fitness; antibiotic cycling; mathematical modeling},
language = {eng},
month = {3},
number = {1},
pages = {129-142},
publisher = {EDP Sciences},
title = {Quantifying the Impact of Bacterial Fitness and Repeated Antimicrobial Exposure on the Emergence of Multidrug-Resistant Gram-Negative Bacilli},
url = {http://eudml.org/doc/222298},
volume = {2},
year = {2010},
}

TY - JOUR
AU - D'Agata, E. M.C.
AU - Horn, M.
AU - Webb, G.
TI - Quantifying the Impact of Bacterial Fitness and Repeated Antimicrobial Exposure on the Emergence of Multidrug-Resistant Gram-Negative Bacilli
JO - Mathematical Modelling of Natural Phenomena
DA - 2010/3//
PB - EDP Sciences
VL - 2
IS - 1
SP - 129
EP - 142
AB - The emergence of multidrug resistance among gram-negative bacilli is complex. Numerous factors need to be considered, including the biological fitness cost of resistance, fitnesscompensatory mutations and frequency and type of antibiotic exposure. A mathematical model evaluating these complex relationships was developed in an individual colonized with strains of pan-susceptible, single-, two- and multidrug-resistant (MDR) gram-negative bacilli (GN). The effect of bacterial fitness, compensatory mutations and the frequency of three-antimicrobial regimen exposure to predominance of multidrug-resistant strains were quantified. The model predicts that initially, in the absence of antibiotic exposure, the biologically fitter pan-susceptible strain predominates over the resistant strains. Over time, the fitness of the MDR strains increases faster with repeated antimicrobial exposure, through compensatory-fitness mutations. Increasing the frequency of exposure to the three-antimicrobial regimen or, increasing the initial fitness of the resistant strains, substantially decreases the time to MDR-GN predominance. The model implies that when MDR-GN strains evolve into strains that are fitter than susceptible strains, a reduction in antimicrobial exposure may not result in a decrease of MDR-GN, since the absence of selective antimicrobial pressure would no longer favor susceptible strains. The model also implies that antimicrobial cycling may promote the emergence of MDR-GN.
LA - eng
KW - multidrug-resistance; gram-negative bacteria; antibiotic resistance; mathematical modeling; bacterial fitness; antibiotic cycling; mathematical modeling
UR - http://eudml.org/doc/222298
ER -