The in vitro activity of ACHN-490, a novel aminoglycoside ("neoglycoside"), was evaluated against 102 multidrug-resistant (MDR) Klebsiella pneumoniae strains, including a subset of 25 strains producing the KPC carbapenemase. MIC50 values for gentamicin, tobramycin, and amikacin were 8 microg/ml, 32 microg/ml, and 2 microg/ml, respectively; MIC90 values for the same antimicrobials were > or = 64 microg/ml, > or = 64 microg/ml, and 32 microg/ml, respectively. ACHN-490 showed an MIC50 of 0.5 microg/ml and an MIC90 of 1 microg/ml, which are significantly lower than those of comparator aminoglycosides. ACHN-490 represents a promising aminoglycoside for the treatment of MDR K. pneumoniae isolates, including those producing KPC beta-lactamase.