Activity of ACHN-490 against meticillin-resistant Staphylococcus aureus (MRSA) isolates from patients in US hospitals.

The activity of ACHN-490 was evaluated against 493 meticillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2009-2010 from 23 US hospitals. The MIC(50) and MIC(90) values (minimal inhibitory concentrations for 50% and 90% of the organisms, respectively) for ACHN-490 were 1 and 2 μg/mL compared with 8 and 32 μg/mL for amikacin, 0.5 and 1 μg/mL for gentamicin and 2 and >16 μg/mL for tobramycin.

Combating evolution with intelligent design: the neoglycoside ACHN-490.

The challenge posed by increasing levels of drug-resistant bacteria world-wide is manifest, and must be dealt with both by new approaches to the use of existing antibiotics and by the introduction of novel drugs. ACHN-490 is the first neoglycoside, or next-generation aminoglycoside, to begin clinical development. ACHN-490 was designed to target key pathogens, particularly gram-negative organisms and those resistant to older antibiotics.

Synthesis and spectrum of the neoglycoside ACHN-490.

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.

In vitro activity of the aminoglycoside antibiotic arbekacin against Acinetobacter baumannii-calcoaceticus isolated from war-wounded patients at Walter Reed Army Medical Center.

We determined the in vitro MIC of arbekacin against 200 Acinetobacter isolates recovered from wounded soldiers. The median MIC was 2 microg/ml (range, 0.5 to > 64 microg/ml).

Temporal appearance of plasmid-mediated quinolone resistance genes.

One hundred fifty AAC(6')-Ib-positive gram-negative isolates collected between 1981 and 1991 were examined by PCR for the presence of the aac(6')-Ib-cr variant and other plasmid-mediated quinolone resistance (PMQR) genes. None had the aac(6')-Ib-cr variant, qnrA, qnrS, qnrC, or qepA, but two strains collected in 1988 had qnrB alleles, making these the earliest known PMQR genes.

Detection of methyltransferases conferring high-level resistance to aminoglycosides in enterobacteriaceae from Europe, North America, and Latin America.

The alteration of ribosomal targets by recently described 16S rRNA methyltransferases confers resistance to most aminoglycosides, including arbekacin. Enterobacteriaceae and nonfermentative bacilli acquired through global surveillance programs were screened for the presence of these enzymes on the basis of phenotypes that were resistant to nine tested aminoglycosides. Subsequent molecular studies determined that 20 of 21 (95.