title: The impact of different antibiotic regimens on the emergence of antimicrobial-resistant bacteria.
abstract: BACKGROUND
  The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address.
  
  
  RESULTS
  A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains.
  
  
  CONCLUSIONS
  The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Erika M C
authors.initials: EM
authors.lastname: D'Agata
authors.forename: Myrielle
authors.initials: M
authors.lastname: Dupont-Rouzeyrol
authors.forename: Pierre
authors.initials: P
authors.lastname: Magal
authors.forename: Damien
authors.initials: D
authors.lastname: Olivier
authors.forename: Shigui
authors.initials: S
authors.lastname: Ruan
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D018014:Gene Transfer Techniques; D006801:Humans; D007107:Immune System; D017053:Infection Control; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008962:Models, Theoretical; D010957:Plasmids
chemical_list: D000900:Anti-Bacterial Agents