Harnessing Intra-Host Strain Competition to Limit Antibiotic Resistance: Mathematical Model Results.
Antibiotic overuse has promoted the spread of antibiotic resistance. To compound the issue, treating individuals dually infected with antibiotic-resistant and antibiotic-vulnerable strains can make their infections completely resistant through competitive release. We formulate mathematical models of transmission dynamics accounting for dual infections and extensions accounting for lag times between infection and treatment or between cure and ending treatment. Analysis using the Next-Generation Matrix reveals how competition within hosts and the costs of resistance determine whether vulnerable and resistant strains persist, coexist, or drive each other to extinction. Invasion analysis predicts that treatment of dually infected cases will promote resistance. By varying antibiotic strength, the models suggest that physicians have two ways to achieve a particular resistance target: prescribe relatively weak antibiotics to everyone infected with an antibiotic-vulnerable strain or give more potent prescriptions to only those patients singly infected with the vulnerable strain after ruling out the possibility of them being dually infected with resistance. Through selectivity and moderation in antibiotic prescription, resistance might be limited.
Department of Mathematics, University of Utah, Salt Lake City, UT, USA. alexbeams2@gmail.com.
Alexander B
AB
Beams
Informatics, Decision Enhancement, and Analytical Sciences (IDEAS) 2.0 Center, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.|Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Damon J A
DJ
Toth
Informatics, Decision Enhancement, and Analytical Sciences (IDEAS) 2.0 Center, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.|Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Karim
K
Khader
Department of Mathematics, University of Utah, Salt Lake City, UT, USA.|Department of Biology, University of Utah, Salt Lake City, UT, USA.
Frederick R
FR
Adler
D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000635:transmission; D024881:Drug Resistance, Bacterial; D006801:Humans; D055641:Mathematical Concepts; D008954:Models, Biological; D000067490:Prescription Drug Overuse
D000900:Anti-Bacterial Agents
Antibiotic resistance; Coinfections; Competitive release; Mathematical modeling; Ordinary differential equations