In vitro activity of plazomicin against β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE)

The Journal of Antimicrobial Chemotherapy
Yunliang ZhangKaren Bush

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat because few drugs are available to treat infections caused by these pathogens. Plazomicin is a novel aminoglycoside that recently completed a Phase 3 clinical trial for treatment of infections caused by CRE. A set of 110 characterized unique CRE patient isolates from central Indiana healthcare centres was tested by microbroth dilution for susceptibility to plazomicin, and to reference aminoglycosides and carbapenems. WGS was conducted to analyse the isolate with an elevated plazomicin MIC. The isolates, 107 of which produced KPC carbapenemases, were 97.3% and 100% non-susceptible to meropenem and imipenem, respectively, with variable rates of non-susceptibility to amikacin (76.4%), gentamicin (18.2%), kanamycin (91.8%) and tobramycin (96.4%). MIC50/MIC90 values for plazomicin were the lowest of all the drugs tested: 0.5/0.5 mg/L for 96 KPC-producing Klebsiella pneumoniae isolates and 0.5/1 mg/L for all 110 carbapenemase-producing isolates. Higher MIC50/MIC90 values were observed for the other antibiotics tested: amikacin (32/32 mg/L), gentamicin (1/16 mg/L), kanamycin (>64/>64 mg/L), tobramycin (32/64 mg/L), imipenem (8/32 mg/L) and meropenem (≥16/≥16 mg/L...Continue Reading

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Citations

Dec 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria S Ramirez, Marcelo E Tolmasky
Sep 13, 2018·Expert Review of Anti-infective Therapy·Matteo BassettiAlessandro Russo
Oct 3, 2018·Antimicrobial Agents and Chemotherapy·Allison S KomirenkoJulie D Seroogy
Jan 4, 2019·Clinical Pharmacology in Drug Development·Taylor ChoiShyeilla V Dhuria
Dec 5, 2018·Pharmacotherapy·Kristy M ShaeerJonathan C Cho
Feb 1, 2019·Clinical Microbiology Reviews·Wenjing WuZhiyong Zong
Jul 11, 2019·Open Biology·Anne WitzkyMichael Ibba
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