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Effects of cefditoren, cefuroxime, cefaclor and cefixime on the competitive growth of Streptococcus pneumoniae, as a model approach to selection of populations

Abstract number: 1733_1556

Cafini F., Torrico M., Gonzalez N., Echevarria O., Sevillano D., Gimenez M.J., Alou L., Aguilar L., Coronel P., Gimeno M., Prieto J.

Objectives: To explore how oral cephalosporins influence the evolution of S. pneumoniae populations sharing the same ecological niche.

Methods: A computerised pharmacodynamic model (J Antimicrob Chemother 2006;58:794–801) simulating physiological concentrations obtained after 400 mg b.i.d. cefditoren (CDN), 500 mg b.i.d. cefuroxime (CXM), 500 mg t.i.d. cefaclor (CEC), and 400 mg o.d. cefixime (CFM) was used to investigate its effect on a mixed culture of four S. pneumoniae serotypes (Ser) as an approach to ecology of population dynamics. MICs (mg/mL) of CDN, CXM, CEC and CFM were: 0.015, 0.03, 0.25, and 0.5 for Ser4 and Ser19A; 0.5, 4, >8 and >8 for Ser19F; and 1, 4, >8 and >8 for Ser23F, respectively. Initial mixed inocula (time 0) of 5×106 to 107 cfu/mL, including similar percentages of each Ser were used.

Results: Mean colony counts in antibiotic-free plates (whole pneumococcal population) increased (from 0 to 12 h) from log10 7.0 to 6.3 in drug-free simulations (control), from log10 6.6 to 3.6 in CDN simulations, from log10 6.6 to 8.0 in CXM simulations, from log10 7.0 to 7.2 in CEC simulations, and from log10 6.7 to 7.4 in CFM simulations. At 12 h of control drug-free experiments, the dominant population was Ser4 (70.0%). The small final population after CDN simulations included 48% Ser23F and 20% Ser19F. With all other compounds, the final population was higher than initial inocula, and corresponded to 90% Ser19F after CXM simulations, 61% Ser19F and 35% Ser23F after CEC simulations, and 96% Ser19F after CFM simulations.

Conclusion: Strain distribution in antibiotic-free environment depends on bacterial fitness in mono- and multi-strain niches. The selective pressures of antimicrobial regimens eradicate some populations and unmask minor populations, thus redistributing the whole population. CDN was the only cephalosporin showing bactericidal activity (≥3 log10 reduction of initial inocula) at 12 h of the whole initial population, with a small remaining population mainly composed by Ser23F. All other oral cephalosporins selected populations higher than initial inocula mainly composed by Ser19F.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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