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JAC Advance Access published online on July 30, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl307
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received January 4, 2006
Revised June 28, 2006
Accepted July 5, 2006

Original article

Effects of antimicrobials on the competitive growth of Streptococcus pneumoniae: a pharmacodynamic in vitro model approach to selection of resistant populations

David Sevillano 1, Lorenzo Aguilar 1, Luis Alou 1, María-José Giménez 1, Olatz Echevarría 1, Fabio Cafini 1, Eva Valero 1, Asunción Fenoll 2, and José Prieto 1 *

1 Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain
2 Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain

* To whom correspondence should be addressed.
José Prieto, E-mail: jprieto{at}med.ucm.es


  Abstract

Objectives: 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.

Keywords: S. pneumoniae; population dynamics; resistance selection; ecology; pharmacodynamics.
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N. Gonzalez, L. Aguilar, L. Alou, M.-J. Gimenez, D. Sevillano, M. Torrico, F. Cafini, P. Coronel, and J. Prieto
Influence of different resistance traits on the competitive growth of Haemophilus influenzae in antibiotic-free medium and selection of resistant populations by different {beta}-lactams: an in vitro pharmacodynamic approach
J. Antimicrob. Chemother., June 1, 2009; 63(6): 1215 - 1222.
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