Novel Carbapenem Antibiotics for Parenteral and Oral Applications: In Vitro and In Vivo Activities of 2-Aryl Carbapenems and Their Pharmacokinetics in Laboratory Animals

摘要: SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae β-lactamase-negative ampicillin-resistant Neisseria gonorrhoeae ciprofloxacin-resistant MIC(90)s ≤ 1 μg/ml. Unlike tebipenem (MIC(50), 8 μg/ml), had no hospital Pseudomonas aeruginosa ≥ 128 μg/ml). The bactericidal activities S. H. were equal or superior to that greater than cefditoren. therapeutic efficacies intravenous administrations experimentally induced in mice caused by cefditoren, respectively, reflecting their vitro activities. showed pharmacokinetics similar those meropenem terms half-life monkeys (0.4 h) stable human dehydropeptidase I. SM-368589 SM-375769, which medoxomil esters SM-369926, good oral bioavailability rats, dogs, (4.2 62.3%). Thus, promising candidates show an ideal broad spectrum for the treatment infections, including influenzae, have low selective pressure on antipseudomonal carbapenem-resistant nosocomial pathogens, allow parenteral, oral, switch therapies.