AM-7359--a novel oxazolidinone with low resistance potential and potent activity against drug resistant pathogens.
AM-7359 is a member of a novel series of oxazolidinones with antimicrobial activity against pathogens resistant to multiple antibiotics. Potent antibiotics with limited drug cross resistance to current therapeutic agents are needed for the treatment of drug resistant pathogens. This study investigated the resistance development to linezolid (LZD) and AM-7359 by key pathogens and the degree of cross resistance between these two oxazolidinones. Both AM-7359 and LZD, demonstrates a low frequency of resistance development. After 30 passages and selection for resistant development of four different Staphylococcus aureus and Enterococus faecium strains the minimum inhibitory concentration (MIC) for AM-7359 was 1 <or= microg/ml compared to 32 to 256 microg/ml for LZD. In cross resistance studies AM-7359 demonstrated MICs of 0.5 to 1 microg/ml against the resistant strains selected on LZD. LZD MICs against the resistant strains selected on AM-7359 were 32-64 microg/ml.
Overbye
K M
KM
Infectious Disease, Merck Research Laboratories, Rahway, New Jersey 07065, USA. karen_oberbye@merck.com
Mordekhay
D
D
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects*; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
C523767:AM-7359; D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid