FIG 3.

Conceptual figure illustrating the evolution of antibiotic-resistant clinical strains of P. aeruginosa subjected to the alternation of ciprofloxacin with aztreonam or tobramycin or to the combination of ciprofloxacin with tobramycin or ciprofloxacin with aztreonam. Evolution starts when different antibiotic-resistant clinical isolates, represented as cells with different colors, are treated with ciprofloxacin or the combinations ciprofloxacin-tobramycin or ciprofloxacin-aztreonam at time zero (t₀). In the case of the alternate treatment, there is a first step of evolution toward ciprofloxacin resistance and CS to tobramycin and aztreonam (green cells), rendering ciprofloxacin ineffective (t_1.1). Then, treatment is switched to tobramycin or aztreonam, which may result in the elimination (represented as a dinosaur fossil skeleton) of cells susceptible to those drugs (t₂). In the case of the combinatory therapy, evolution consists in a single treatment of the different antibiotic-resistant clinical isolates (t₀) with ciprofloxacin-tobramycin or ciprofloxacin-aztreonam. Since the acquisition of ciprofloxacin resistance may lead to CS to tobramycin and aztreonam, it could be expected that drug combinations result in a reduced rate of adaptation or the extinction (represented as a dinosaur fossil skeleton) of cells (t_1.2).