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

E. M.C. D'Agata; M. Horn; G. Webb

Mathematical Modelling of Natural Phenomena (2010)

- Volume: 2, Issue: 1, page 129-142
- ISSN: 0973-5348

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topD'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 -

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