title: Effects of antimicrobials on the competitive growth of Streptococcus pneumoniae: a pharmacodynamic in vitro model approach to selection of resistant populations.
abstract: OBJECTIVE
  To investigate antimicrobial effects on a mixed culture of five Streptococcus pneumoniae serotypes (S) as an approach to ecology of population dynamics.
  
  
  METHODS
  A computerized pharmacodynamic model simulating concentrations obtained after levofloxacin, ciprofloxacin and azithromycin doses was used. Resistance patterns were S12, susceptible to study drugs; S31, low-level macrolide-resistant (efflux phenotype); S11, high-level macrolide-resistant (erm genotype); S9V, low-level quinolone-resistant; and S3, high-level quinolone-resistant. Initial mixed inocula (time 0) included similar percentages of each serotype.
  
  
  RESULTS
  At 24 h of control drug-free experiments, dominant strains were S9V (57.4%) and S12 (41.8%) with marginal populations of S31, S3 and S11. Azithromycin selected to a much higher extent the strain with low-level resistance to macrolides (S31) rather than the strain with high-level resistance (S11) (accounting for 99.9% versus 0.1% of the total population at 24 h). Ciprofloxacin selected to a higher extent low-level (S9V) rather than high-level (S3) quinolone resistance (72.4% versus 27.6%). Levofloxacin decreased the proportion of the predominant S9V in controls to 22.2% (an intermediate-resistant strain with MIC = 4 mg/L) and unmasked the high-level resistant strain (MIC = 32 mg/L) up to 77.8%.
  
  
  CONCLUSIONS
  Strain distribution in an antibiotic-free environment depends on bacterial fitness in mono- and multi-strain niches. Selective pressure of antimicrobial regimens eradicate some populations and unmask minor populations, thus redistributing the whole population. Selective potential only for resistance phenotypes with very low prevalence (such as high-level quinolone resistance) in the community should be preferred to that selecting more prevalent resistance phenotypes.
authors.affiliation: Microbiology Department, School of Medicine, Universidad Complutense Avda. Complutense s/n, 28040 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sevillano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Aguilar
authors.forename: Luis
authors.initials: L
authors.lastname: Alou
authors.forename: María-José
authors.initials: MJ
authors.lastname: Giménez
authors.forename: Olatz
authors.initials: O
authors.lastname: Echevarría
authors.forename: Fabio
authors.initials: F
authors.lastname: Cafini
authors.forename: Eva
authors.initials: E
authors.lastname: Valero
authors.forename: Asunción
authors.initials: A
authors.lastname: Fenoll
authors.forename: José
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D017753:Ecosystem; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D008954:Models, Biological; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000254:growth & development*
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media