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Carbapenemshave potent antibacterial activity and a wide spectrum of action against Gram-positive and Gram-negative bacteria1~4). They also show high in vitro and in vivo antibacterial activity against Pseudomonas aeruginosa, which is a clinically important organism. P. aeruginosa, a commonsoil and water bacterium, is associated with acute and chronic infections of humans5). P. aeruginosa is highly resistant to many antibiotics6), mainly because of the permeation barrier to drugs through the outer membrane7). The high activity of carbapenems against this organism is due to their good diffusion through the outer membrane8'9), high affinity for penicillin-binding proteins (PBPs)10) and high stability and inhibitory activity against /Mactamases11*. Recently, carbapenem-resistant P. aeruginosa strains have been isolated clinically12' 13). Most of them lack outer membraneprotein D2 (OprD2) which forms a specific porin channel for basic amino acids and carbapenem antibiotics9' 14). Investigation of imipenemresistant P. aeruginosa strains revealed that meropenem still showed good activity against these strains. This result was in agreement with that from a previous report15). Weisolated two genetically distinct meropenem-resistant mutants, designated rnpmAand mpmB mutants. The mpmAand mpmBwere thought to'be alleles of oprD216) and nalBll\ respectively, both related to diffusion of meropenemthrough the outer membrane.These mutants showed different susceptibility profiles to carbapenems (data not shown). In this report, we examined the antipseudomonal activities of carbapenems affected by oprD2and nalB mutations, with regard to structureactivity relationships, especially l /?-methyl group and the basicity in C-2 side chain. Carbapenem compounds, shown in Fig. 1, were prepared in SumitomoPharmaceuticals Research Center, Osaka, Japan, according to the reported proce-dures18^2^. P. aeruginosa PAO2152 and TL2666 were laboratory and clinically isolated strains, respectively,

Amongthe manyclinical pathogens Pseudomonas aeruginosa is understood as the bacterium that causes opportunistic infections in patients under immunosuppressed conditions or with cystic fibrosis or diffuse panbronchiolitis.

In the previous papers1'2*, we reported that carbapenem derivatives having a 5'-substituted pyrrolidinylthio group at the C-2 position exhibited broad and strong antibacterial activity. Some of them also showed high stability to renal dehydropeptidase-I (DHP-I). It is known that the plasma