Mutation rate and the efficacy of antimicrobial drug treatment.
Despite rapid progress in drug development, microbial infections in general are becoming increasingly difficult to treat as a result of the emergence of drug-resistant strains. In some cases, such as HIV-1, the early goal of eradicating infections with antimicrobial drugs is, for now, being replaced with the more pragmatic goal of controlling infections over long periods of time through a succession of transiently effective treatments. Because treatment efficacy is often incomplete, studying the degree of treatment efficacy has great relevance to clinical disease management. We derived a model describing the association between the mutation rate of the pathogen and the degree of treatment efficacy. We found that drug treatment is most effective when the mutation rate of the pathogen is either very low or, perhaps counterintuitively, very high. We discuss this finding in the light of a promising new treatment strategy for RNA viruses that combines antiviral compounds with a mutagen.
Gerrish
Philip J
PJ
Department of Applied Mathematics, Instituto Mexicano del Petróleo, Colonia San Bartolo Atepehuacan, Distrito Federal, México. pgerrish@yahoo.com
García-Lerma
J Gerardo
JG
D000998:Antiviral Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008957:Models, Genetic; D009154:Mutation
D000998:Antiviral Agents