RT Journal Article
SR Electronic
T1 Predicting drug resistance evolution: antimicrobial peptides vs. antibiotics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 138107
DO 10.1101/138107
A1 Yu, Guozhi
A1 Baeder, Desiree Y
A1 Regoes, Roland R
A1 Rolff, Jens
YR 2017
UL http://biorxiv.org/content/early/2017/05/23/138107.abstract
AB Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides are considered part of a solution to this problem, because they are new agents that add to our repertoire. Importantly, antimicrobial peptides differ fundamentally from antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against antimicrobial peptides and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against antimicrobial peptides. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is therefore widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.