Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment
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Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment. / Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Olsen, John Elmerdahl; Nielsen, Soren Saxmose.
I: B M C Microbiology, Bind 16, 118, 23.06.2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment
AU - Ahmad, Amais
AU - Zachariasen, Camilla
AU - Christiansen, Lasse Engbo
AU - Græsbøll, Kaare
AU - Toft, Nils
AU - Matthews, Louise
AU - Olsen, John Elmerdahl
AU - Nielsen, Soren Saxmose
PY - 2016/6/23
Y1 - 2016/6/23
N2 - BackgroundCombination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.ResultsSimulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.ConclusionSequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.
AB - BackgroundCombination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.ResultsSimulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.ConclusionSequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.
KW - Antimicrobial resistance
KW - Ampicillin
KW - Tetracycline
KW - Pharmacodynamic
KW - Dosing strategies
KW - Pig
KW - Bacterial growth
U2 - 10.1186/s12866-016-0724-5
DO - 10.1186/s12866-016-0724-5
M3 - Journal article
C2 - 27338861
VL - 16
JO - BMC Microbiology
JF - BMC Microbiology
SN - 1471-2180
M1 - 118
ER -
ID: 164109957