In vitro and in vivo antibacterial activities of SM-216601, a new broad-spectrum parenteral carbapenem.
SM-216601 is a novel parenteral 1beta-methylcarbapenem. In agar dilution susceptibility testing, the MIC of SM-216601 for 90% of the methicillin-resistant Staphylococcus aureus (MRSA) strains tested (MIC(90)) was 2 microg/ml, which was comparable to those of vancomycin and linezolid. SM-216601 was also very potent against Enterococcus faecium, including vancomycin-resistant strains (MIC(90) = 8 microg/ml). SM-216601 exhibited potent activity against penicillin-resistant Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, with MIC(90)s of less than 0.5 microg/ml, and intermediate activity against Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa. The therapeutic efficacy of SM-216601 against experimentally induced infections in mice caused by S. aureus, E. faecium, E. coli, and P. aeruginosa reflected its in vitro activity and plasma level. Thus, SM-216601 is a promising candidate for nosocomial bacterial infections caused by a wide range of gram-positive and gram-negative bacteria, including multiresistant pathogens.
Ueda
Yutaka
Y
Sumitomo Pharmaceuticals Research Division, Konohana, Osaka, Japan. yutakau@sumitomopharm.co.jp
Kanazawa
Katsunori
K
Eguchi
Ken
K
Takemoto
Koji
K
Eriguchi
Yoshiro
Y
Sunagawa
Makoto
M
D000038:Abscess / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D015780:Carbapenems / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013293:Enterococcus faecalis / Q000187:drug effects / Q000472:pathogenicity; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012015:Reference Standards
D000900:Anti-Bacterial Agents; D015780:Carbapenems