Transcriptomic responses of a New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae isolate to the combination of polymyxin B and chloramphenicol
Nusaibah Abdul Rahim, Soon-Ee Cheah, Matthew D Johnson, Yan Zhu, Heidi H Yu, Hanna E Sidjabat, Mark S Butler, Matthew A Cooper, Jing Fu, David L Paterson, Roger L Nation, John D Boyce, Phillip J Bergen, Tony Velkov, Jian Li
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | ELSEVIER | Published : 2020
The combination of polymyxins and chloramphenicol possesses synergistic killing activity against New Delhi metallo-β-lactamase (NDM)-producing Klebsiella pneumoniae. This systems study examined the transcriptomic responses to the polymyxin/chloramphenicol combination in clinical NDM-producing K. pneumoniae isolate S01. Klebsiella pneumoniae S01 (initial inoculum ~108 CFU/mL) was treated with polymyxin B (1 mg/L, continuous infusion) or chloramphenicol [maximum concentration (Cmax) = 8 mg/L, half-life (t1/2) = 4 h], alone or in combination, using an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model to mimic their pharmacokinetics in patients. Transcriptomic profiles of bacterial samples ..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
This study was partially funded by the Australian National Health and Medical Research Council (NHMRC) [APP1046561]. JL and TV are supported by research grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI132681]. JL and MAC are Australian NHMRC Principal Research Fellows. TV is an Australian NHMRC Career Development Research Fellow. DLP is an Australian NHMRC Practitioner Fellow.