inducible AmpC expression, poor membrane permeability, and efflux pumps make Pseudomonas resistant to most beta lactams. The clinical efficacy of carbapenems in Pseudomonas infection arises in part because, while they are strong inducers of AmpC, they are poor substrates. The identification of Pseudomonas strains that produce beta lactamases capable of cleaving carbapenems, such as the New Delhi metallo beta lactamase has raised increasing concern regarding the potential for an era of untreatable Pseudomonas infections. Structure In terms of structure, the carbapenems are very similar to the penicillins (penams), but the sulfur atom in position 1 of the structure has been replaced with a carbon atom, and an unsaturation has been introduced—hence the name of the group, the carbapenems. Groups Carbapenems are further broken down into groups with ertapenem being the lone member of group 1. Group 2 carbapenems (imipenem, meropenem, and doripenem) are identified by their efficacy with respect to multiresistant gram-negative (MDRGN) bacteria such as Pseudomonas and Acinetobacter species. Biosynthesis The carbapenems are thought to share their early biosynthetic steps in which the core ring system is formed. Malonyl-CoA is condensed with glutamate-5-semialdehyde with concurrent formation of the five-membered ring. Next, a β-lactam synthetase uses ATP to form the β-lactam and the saturated carbapenam core. Further oxidation and ring inversion provides the basic carbapenem . Administration Due to their expanded spectra, the desire to avoid generation of resistance and the fact that, in general, they have poor oral bioavailability, they are administered intravenously in hospital settings for more serious infections. However, research is underway to develop an effective oral carbapenem. See also Faropenem is closely related, but it is a penem, not a carbapenem. Antimicrobial resistance NDM-1 is an enzyme that introduces bacterial resistance to carbapenem antibiotics via hydrolysis of the carbapenem backbone, thereby inactivating its ability to inhibit cell wall synthesis. References External links Structure Activity Relationships "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD; beginning at pp131 Page 2: Ertapenem vs. Meropenem: Equivalency of Clinical and Microbiological Outcomes. 2010