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Antimicrobial Agents and Chemotherapy, October 2009, p. 4504-4507, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00556-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

ACHN-490, a Neoglycoside with Potent In Vitro Activity against Multidrug-Resistant Klebsiella pneumoniae Isolates{triangledown}

Andrea Endimiani,1,2* Kristine M. Hujer,1,2 Andrea M. Hujer,1 Eliana S. Armstrong,3 Yuvraj Choudhary,1 James B. Aggen,3 and Robert A. Bonomo1,2,4,5*

Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio,1 Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio,2 Achaogen, Inc., South San Francisco, California,3 Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio,4 Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio5

Received 24 April 2009/ Returned for modification 31 May 2009/ Accepted 1 August 2009

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 µg/ml, 32 µg/ml, and 2 µg/ml, respectively; MIC90 values for the same antimicrobials were ≥64 µg/ml, ≥64 µg/ml, and 32 µg/ml, respectively. ACHN-490 showed an MIC50 of 0.5 µg/ml and an MIC90 of 1 µg/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 β-lactamase.

* Corresponding author. Mailing address: Infectious Diseases Section, Department of Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44106 Phone: (216) 791-3800, ext. 4399. Fax: (216) 231-3482. E-mail for Robert A. Bonomo: robert.bonomo{at}va.gov. E-mail for Andrea Endimiani: aendimiani{at}gmail.com

{triangledown} Published ahead of print on 21 September 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4504-4507, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00556-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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