title: Antibiotic innovation may contribute to slowing the dissemination of multiresistant Streptococcus pneumoniae: the example of ketolides.
abstract: BACKGROUND
  Despite increasingly frequent bacterial resistance to antibiotics, antibacterial innovation is rare. Ketolides constitute one of the very few new antibiotic classes active against Streptococcus pneumoniae developed during the last 25 years. Their mechanism of action resembles that of macrolides, but they are unaffected by common resistance mechanisms. However, cross-resistance to ketolides has been observed in some macrolide-resistant strains. We examined how new antibiotic exposure may affect overall pneumococcal resistance patterns in the population. The aims of this study were to assess the potential dissemination of newly emerged resistances and to control the selection of strains already multiresistant to existing antimicrobials.
  
  
  RESULTS
  We developed an age-structured population model for S. pneumoniae transmission in a human community exposed to heptavalent vaccine, and beta-lactams, macrolides and ketolides. The dynamics of intra-individual selection of resistant strains under antibiotic exposure and interindividual transmission were simulated, with antibiotic-specific resistance mechanisms defining the path to co-resistances and cross-resistances, and parameters concerning the French situation. Results of this simulation study suggest that new antibiotic consumption could markedly slow the diffusion of multiresistant strains. Wider use was associated with slower progression of multiresistance. When ketolides were prescribed to all ages, resistance to them reached 10% after >15 years, while it took >40 years when they were prescribed only to adults. In the scenario according to which new antibiotics totally replaced former antimicrobials, the beta-lactam resistance rate was limited at 70%.
  
  
  CONCLUSIONS
  In a context of widespread vaccination and rational use of antibiotics, innovative antibiotic, prescribed to all age groups, may have an added impact on multiresistant-strain dissemination in the population.
authors.affiliation: Unité de Pharmacoépidémiologie et Maladies Infectieuses, Institut Pasteur, Paris, France. lopatows@pasteur.fr
authors.forename: Lulla
authors.initials: L
authors.lastname: Opatowski
authors.forename: Laura
authors.initials: L
authors.lastname: Temime
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Varon
authors.forename: Roland
authors.initials: R
authors.lastname: Leclercq
authors.forename: Roland
authors.initials: R
authors.lastname: Leclerc
authors.forename: Henri
authors.initials: H
authors.lastname: Drugeon
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boëlle
authors.forename: Didier
authors.initials: D
authors.lastname: Guillemot
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003710:Demography; D024881:Drug Resistance, Bacterial; D004352:Drug Resistance, Microbial; D005602:France / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D048628:Ketolides / Q000627:therapeutic use*; D010406:Penicillins / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D018074:Vaccines, Conjugate / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D048628:Ketolides; D010406:Penicillins; D018074:Vaccines, Conjugate