Polymyxin Resistance in Acinetobacter baumannii: Genetic Mutations and Transcriptomic Changes in Response to Clinically Relevant Dosage Regimens
Soon-Ee Cheah, Matthew D Johnson, Yan Zhu, Brian T Tsuji, Alan Forrest, Jurgen B Bulitta, John D Boyce, Roger L Nation, Jian Li
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2016
Polymyxins are often last-line therapeutic agents used to treat infections caused by multidrug-resistant A. baumannii. Recent reports of polymyxin-resistant A. baumannii highlight the urgent need for research into mechanisms of polymyxin resistance. This study employed genomic and transcriptomic analyses to investigate the mechanisms of polymyxin resistance in A. baumannii AB307-0294 using an in vitro dynamic model to mimic four different clinically relevant dosage regimens of polymyxin B and colistin over 96 h. Polymyxin B dosage regimens that achieved peak concentrations above 1 mg/L within 1 h caused significant bacterial killing (~5 log10CFU/mL), while the gradual accumulation of colisti..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases at the National Institutes of Health
Awarded by NHMRC
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This study was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (Award Numbers R01AI079330 to R.L.N., J.L., B.T.T. and J.B.B. and R01AI111990 to B.T.T., J.L., R.L.N., J.D.B. and J.B.B.). J.L. is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow. J.B.B. is the recipient of an NHMRC Career Development Fellowship (APP1084163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.