Synthesis and Spectrum of the Neoglycoside ACHN-490

被引：191

作者：

Aggen, James B. ^{[1
]}

Armstrong, Eliana S. ^{[1
]}

Goldblum, Adam A. ^{[1
]}

Dozzo, Paola ^{[1
]}

Linsell, Martin S. ^{[1
]}

Gliedt, Micah J. ^{[1
]}

Hildebrandt, Darin J. ^{[1
]}

Feeney, Lee Ann ^{[1
]}

Kubo, Aya ^{[1
]}

Matias, Rowena D. ^{[1
]}

Lopez, Sara ^{[1
]}

Gomez, Marcela ^{[1
]}

Wlasichuk, Kenneth B. ^{[1
]}

Diokno, Raymond ^{[1
]}

Miller, George H. ^{[1
]}

Moser, Heinz E. ^{[1
]}

机构：

[1] Achaogen Inc, San Francisco, CA 94080 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 11期

关键词：

AMINOGLYCOSIDE RESISTANCE MECHANISMS; INFECTIONS; ANTIBIOTICS;

D O I：

10.1128/AAC.00572-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

ACHN-490 is a neoglycoside, or "next-generation" aminoglycoside (AG), that has been identified as a potentially useful agent to combat drug-resistant bacteria emerging in hospitals and health care facilities around the world. A focused medicinal chemistry campaign produced a collection of over 400 sisomicin analogs from which ACHN-490 was selected. We tested ACHN-490 against two panels of Gram-negative and Gram-positive pathogens, many of which harbored AG resistance mechanisms. Unlike legacy AGs, ACHN-490 was active against strains expressing known AG-modifying enzymes, including the three most common such enzymes found in Enterobacteriaceae. ACHN-490 inhibited the growth of AG-resistant Enterobacteriaceae (MIC90, <= 4 mu g/ml), with the exception of Proteus mirabilis and indole-positive Proteae (MIC90, 8 mu g/ml and 16 mu g/ml, respectively). ACHN-490 was more active alone in vitro against Pseudomonas aeruginosa and Acinetobacter baumannii isolates with AG-modifying enzymes than against those with altered permeability/efflux. The MIC90 of ACHN-490 against AG-resistant staphylococci was 2 mu g/ml. Due to its promising in vitro and in vivo profiles, ACHN-490 has been advanced into clinical development as a new antibacterial agent.

引用

页码：4636 / 4642

页数：7

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