Autor: |
Thi Khanh Nhu N; The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Riordan DW; Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London., Do Hoang Nhu T; The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam., Thanh DP; The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam., Thwaites G; The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom., Huong Lan NP; The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam., Wren BW; Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London., Baker S; The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.; Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London.; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom., Stabler RA; Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London. |
Abstrakt: |
Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256 μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile. |