In vitro activity of Plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying enzymes most common in US Census divisions.

Aminoglycoside-nonsusceptible isolates of Escherichia coli, Klebsiella, Proteus, and Enterobacter species (480/3675) from US hospitals collected during 2014-2015 were screened for 16S rRNA methyltransferase and aminoglycoside-modifying enzyme (AME) genes. Only 5 isolates had high aminoglycoside MICs and carried 16S rRNA methyltransferases. AME genes were observed among 89.7% (426/475) of isolates and the most common genes were aac(3)-IIa (n = 270) and aac(6')-Ib (n = 269). Among other genes, ant(2″)-Ia, aac(3)-Iva, and aph(3')-VIa were observed among 36, 23, and 3 isolates, respectively. Forty-nine (10.3%) isolates yielded negative results for the investigated AME genes. Plazomicin (MIC50/90, 0.5/1 μg/ml) inhibited 99.3% of the AME-carrying isolates at its susceptible breakpoint while amikacin, gentamicin, and tobramycin inhibited 90.1%, 20.9%, and 18.3%, respectively. Plazomicin was approved by the US Food and Drug Administration in June 2018 for the treatment of complicated urinary tract infections when limited treatment options are available. This agent displayed activity against isolates carrying AMEs that were resistance to other aminoglycosides and comparator agents.