Drug-Induced Tolerance: The Effects of Antibiotic Pre-Exposure in Stenotrophomonas Maltophilia

Abstract

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.

Keywords::

• antibiotic-induced persistence
• cross-persistence
• daptomycin
• Stenotrophomonas maltophilia
• tolerance

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fmb-2019-0253

Author contributions

MAM Ferreira and KV dos Santos conceived of the study design. KV dos Santos provided the facilities and supplies for the study, also revised the manuscript and indicated changes in experiments. MAM Ferreira and MLS Pereira performed the microbiological assays. All authors contributed to the analysis of the results and the writing of the manuscript. All authors approved the final version of the manuscript.

Acknowledgments

The authors would like to thank AC Gales and R Cayô da Silva from Universidade Federal de São Paulo (UNIFESP) as well as all the members of Alerta Laboratory for their support with the biomolecular experiments. They also thank the Department of Pathology at UFES for the experimental support and the Pró-Reitoria de Pesquisa e Pós-Graduação at UFES for the language services provided. Special thanks to SS Gonçalves from UFES.

Financial & competing interests disclosure

This study was supported by Fundação de Amparo à Pesquisa e Inovação do Espírito Santo – FAPES (grant number 67663397/2014). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES, finance code 001. MAM Ferreira received a scholarship from CAPES, Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by Fundação de Amparo à Pesquisa e Inovação do Espírito Santo – FAPES (grant number 67663397/2014). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES, finance code 001. MAM Ferreira received a scholarship from CAPES, Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.