Fig. 8.

Conceptual figure illustrating two different evolutionary approaches to drive different antibiotic resistant mutants of P. aeruginosa to extinction. Different genetic backgrounds of P. aeruginosa (t₀) show a robust evolution toward CS to tobramycin after short-term evolution in the presence of ceftazidime (t₁) (Hernando-Amado et al. 2020). Furthermore, these CAZ^RTOB^S mutants also have a high fitness cost in antibiotic-free environments. Therefore, it is possible to alternate the use of ceftazidime with periods of drug restriction, allowing the compensation of fitness costs and the decline of ceftazidime resistance (t₂), or with tobramycin (Hernando-Amado et al. 2020), driving the populations to extinction (t₂). In the second case, the hypothetical presence of sublethal tobramycin concentrations in certain situations, although selecting an increase of tobramycin resistance, would also lead to a decline of ceftazidime resistance in these populations. Therefore, a switch back to ceftazidime in either of the two strategies could finally result in the extinction of the resistant populations (t₃).