The present model has shown that combining was slightly more efficient than mixing and cycling with regard to minimizing infection. Regarding double resistance emergence, both mixing and cycling were more efficient than combining when variation is stress induced.
The authors have described the limits of their work: they did not consider the possible fitness cost of antibiotic resistance or the influence of stochastic events (epidemic outbursts of bacteria and extinction of rare bacterial strains for long periods of time, human errors in the form of dosage errors, lack of compliance to hospital guidelines) on the dynamics. Other limiting factors were also mentioned such as patient age, relative efficiency of the different antibiotics and drug interactions. In our opinion, other limits could also have been mentioned: the problems of non-adherence, self-medication, outpatient antibiotic use, and the state of immunosuppression of the patient treated.
Mathematical models such as that built by Obolski and Hadany are an important step in regulating the consumption of antibiotics. The originality in this model is the study of stress-induced genetic variation mechanisms on resistance emergence and minimization of infection. However, in the literature, it is usual that models consider only a single pathogen or a single mechanism of resistance acquisition and it is not clear that they can be applied to other clinical situations. At the same time, with the aim to try to stop the continuing spiral of resistance it is necessary to develop other research programs: campaigns to educate the public and healthcare workers [9
], novel avenues for drugs targeting against infectious agents [10
], the development of phage strategies [12
] and new conjugate vaccines [14
], the use of new agents such as probiotics or antivirulence drugs [15
], and the use of new diagnostic tools to differentiate colonization from infection [17
]. Only with a multidisciplinary approach will win the fight against MDR bacteria.