Hydrolysis and inhibition profiles of beta-lactamases from molecular classes A to D with doripenem, imipenem, and meropenem.
The stability of doripenem to hydrolysis by beta-lactamases from molecular classes A to D was compared to the stability for imipenem and meropenem. Doripenem was stable to hydrolysis by extended-spectrum beta-lactamases and AmpC type beta-lactamases and demonstrated high affinity for the AmpC enzymes. For the serine carbapenemases SME-3 and KPC-2 and metallo-beta-lactamases IMP-1 and VIM-2, doripenem hydrolysis was generally 2- to 150-fold slower than imipenem hydrolysis. SPM-1 hydrolyzed meropenem and doripenem fourfold faster than imipenem.
Queenan
Anne Marie
AM
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202 South, Raritan, NJ 08869, USA. aqueenan@its.jnj.com
Shang
Wenchi
W
Flamm
Robert
R
Bush
Karen
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D015780:Carbapenems / Q000494:pharmacology*; D000077726:Doripenem; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006868:Hydrolysis; D015378:Imipenem / Q000494:pharmacology*; D007700:Kinetics; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004791:Enzyme Inhibitors; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; D000077726:Doripenem; D000077731:Meropenem