In Vitro and In Vivo Antibacterial Activities of SM-216601, a New Broad-Spectrum Parenteral Carbapenem

Abstract

SM-216601 is a novel parenteral 1␤-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 g/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 g/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 g/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.

The Mode of Action of 2-(Thiazol-2-ylthio)-1β-methylcarbapenems against Pseudomonas aeruginosa: The Impact of Outer Membrane Permeability and the Contribution of MexAB-OprM Efflux System

“…Moreover, this carbapenem showed favorable pharmacokinetics in mice, rats, dogs, and cynomolgus monkeys, suggesting a long-acting pharmacokinetic profile in humans, and exhibited decreased convulsant activity in mice. Thus, SMP-601 should be a promising candidate as a broadspectrum b-lactam antibiotic [3].…”

One ring to rule them all: Current trends in combating bacterial resistance to the β‐lactams

“…Future prospects for anti MRSA drugs include the late generation carbapenem razupenem, which has high affinity for MRSA PBP2a as well as pbp5R from ampicillin resistant E. faecium. 66 The C-2 thiazole side chain of razupenem is likely responsible for the observed inhibition of these low-affinity PBPs. A novel class of non-b-lactam based PBP2a inhibitors (oxadiazoles) have displayed excellent bactericidal antibiotic properties against MRSA in vivo.…”

New perspectives on antibacterial drug research

“…Razupenem is also a novel 1β-methylcarbapenem which acts against MDR Gram-positive and Gram-negative bacteria, especially MRSA and vancomycin-resistant Enterococcus (VRE), and may be a promising candidate for the treatment of nosocomial infections. It has lower activity against P. aeruginosa than comparable carbapenems (imipenem, meropenem) [21]. Tebipenem pivoxil is a prodrug whose active metabolite was shown to kill various groups of bacteria, including penicillin-nonsusceptible S. pneumoniae.…”