Drug-induced tolerance: the effects of antibiotic pre-exposure in Stenotrophomonas maltophilia.

Aim: To investigate if the prior use of nontargeted antibiotics induces cross-tolerance in Stenotrophomonas maltophilia. Methods: Antibiotic induction was performed to evaluate daptomycin and vancomycin as possible tolerance-inducing drugs measured by minimum bactericidal concentration/minimum inhibitory concentration (MIC) ratio, adapted disk-diffusion tests and time-kill curves. Results: After antibiotic exposure, three potentially tolerant strains were isolated, maintaining the same MIC value of levofloxacin, with minimum bactericidal concentration/MIC ratio slightly higher than the parental. In the adapted disk-diffusion test, one strain (D25) showed high tolerance level for levofloxacin, ceftazidime and ticarcillin-clavulanate. In time-kill activity of levofloxacin, D25 presented a subpopulation of persisters with survival rate higher (1.6-fold) than the parental. Conclusion: Previous exposure of S. maltophilia to daptomycin can induce cross-tolerance to ceftazidime and ticarcillin-clavulanate and cross-persistence to levofloxacin.