In vitro activities of ME1036 (CP5609), a novel parenteral carbapenem, against methicillin-resistant staphylococci.
ME1036, formerly CP5609, is a novel parenteral carbapenem with a 7-acylated imidazo[5,1-b]thiazole-2-yl group directly attached to the carbapenem moiety of the C-2 position. The present study evaluated the in vitro activities of ME1036 against clinical isolates of gram-positive and gram-negative bacteria. ME1036 displayed broad activity against aerobic gram-positive and gram-negative bacteria. Unlike other marketed beta-lactam antibiotics, ME1036 maintained excellent activity against multiple-drug-resistant gram-positive bacteria, such as methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae (PRSP). The MICs of this compound at which 90% of isolates were inhibited were 2 microg/ml for methicillin-resistant Staphylococcus aureus (MRSA), 2 microg/ml for methicillin-resistant coagulase-negative staphylococci, and 0.031 microg/ml for PRSP. In time-kill studies with six strains of MRSA, ME1036 at four times the MIC caused a time-dependent decrease in the numbers of viable MRSA cells. The activity of ME1036 against MRSA is related to its high affinity for penicillin-binding protein 2a, for which the 50% inhibitory concentration of ME1036 was approximately 300-fold lower than that of imipenem. In conclusion, ME1036 demonstrated a broad antibacterial spectrum and high levels of activity in vitro against staphylococci, including beta-lactam-resistant strains.
Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. mizuyo_kurazono@meiji.co.jp
Mizuyo
M
Kurazono
Takashi
T
Ida
Keiko
K
Yamada
Yoko
Y
Hirai
Takahisa
T
Maruyama
Eiki
E
Shitara
Minoru
M
Yonezawa
D001426:Bacterial Proteins / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006602:Hexosyltransferases / Q000378:metabolism; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; C490527:ME1036; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase