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In vitro activity of Plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying

Mariana Castanheira1, Andrew P Davis1, Alisa W Serio2

  • 1JMI Laboratories, North Liberty, IA 52317.

Diagnostic Microbiology and Infectious Disease
|January 22, 2019
PubMed

Insights

Aminoglycoside-modifying enzyme (AME) genes are common in resistant Gram-negative bacteria. Plazomicin effectively inhibits AME-carrying isolates, offering a vital option for difficult-to-treat infections.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Infectious Diseases

Background:

  • Aminoglycoside resistance is a growing threat in Gram-negative bacterial infections.
  • Aminoglycoside-modifying enzymes (AMEs) are a primary mechanism of resistance.
  • Limited treatment options exist for infections caused by aminoglycoside-resistant bacteria.

Purpose of the Study:

  • To screen aminoglycoside-nonsusceptible Gram-negative isolates for AME and 16S rRNA methyltransferase genes.
  • To evaluate the in vitro activity of plazomicin against these resistant isolates.
  • To compare plazomicin's efficacy with other aminoglycosides.

Main Methods:

  • Screening of 480 Gram-negative isolates from US hospitals (2014-2015) for resistance genes.
  • Detection of 16S rRNA methyltransferase and AME genes using molecular methods.
  • Antimicrobial susceptibility testing, including minimum inhibitory concentrations (MICs) for plazomicin and comparators.

Main Results:

  • AME genes were found in 89.7% of isolates; common genes included aac(3)-IIa and aac(6')-Ib.
  • Only 5 isolates carried 16S rRNA methyltransferases.
  • Plazomicin demonstrated potent activity (MIC50/90, 0.5/1 μg/ml), inhibiting 99.3% of AME-carrying isolates, significantly outperforming amikacin, gentamicin, and tobramycin.

Conclusions:

  • AME genes are prevalent in aminoglycoside-nonsusceptible Gram-negative bacteria.
  • Plazomicin exhibits significant in vitro activity against a broad range of AME-producing Gram-negative pathogens.
  • Plazomicin represents a valuable therapeutic option for complicated urinary tract infections with limited treatment choices.
Keywords:
Aminoglycoside-modifying enzymeAminoglycosidesPlazomicin

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