The Art of Fusion: From Penams and Cephems to Penems

Abstract

This synopsis of published literature summarises the key chemical and bacteriological characteristics of penicillins, i.e. penams, cephalosporins, i.e. cephems, and their hybrid structure, i.e. the penems. Consequently, the antibacterial spectrum of a typical penem, e.g. faropenem, encompasses gram-positive as well as gram-negative species. Dependent from the substituents at position 1 of the five-membered saturated ring fused to the beta-lactam ring oxa-, carba-, or thiopenems can be differentiated. A major determinant of their antibacterial activity and CNS-excitatory potential, however, is the C-2 side chain. The excitatory potential correlates with the basicity of the C-2 side chain as does their antibacterial activity against gram-negative species and non-fermenters like P. aeruginosa. Lipophilicity is a determinant for good in vitro activity against gram-positive bacteria. Several investigational penems exhibit interesting antibacterial spectra, encompassing methicillin resistant staphylococci, enterococci and even P. aeruginosa due to their improved binding affinity to both wild-type and modified low-affinity penicillin binding proteins. The development of these agents may offer therapeutic alternatives for the management of infections.

Kinetics and Quantification of Antibacterial Effects of Beta-Lactams, Macrolides, and Quinolones against Gram-Positive and Gram-Negative RTI Pathogens

“…Penems like imipenem and meropenem [27][28][29] or the newer ones like artapenem and faropenem [30,31] show increasing bacterial killing with increasing concentrations. Consequently, there is a significant trend toward shorter time periods with C > MIC with penems [31,32] as compared to penams or cephems. These findings on the pharmacodynamic characteristics validate the theory that carbapenems and penems are not typical of the beta-lactam class.…”

Novel Penicillins Synthesized by Biotransformation Using Laccase from Trametes spec.

“…6) Much effort has been devoted to the discovery of drugs which would not be cleaved by b-lactamases of pathogenic strains and which have suitable physicochemical and pharmacodynamic profiles. 7,8) The modifications of b-lactam antibiotics could not keep pace with the development of resistance in the pathogenic microorganisms, so that numerous bacteria, among them multidrug resistant Staphylococcus strains, can no longer be treated with the currently available b-lactam antibiotics. 1,9,10) Besides the modification of existing antibiotics by chemical or biochemical methods the coupling of presently used antibiotics with other bioactive compounds or components from them which are not in use till now is a promising way to generate novel molecules with improved therapeutic properties.…”

Antimicrobial Development in the Era of Emerging Resistance

“…Faropenem has a wide spectrum of activity against both aerobic and anaerobic microorganisms and, unlike carbapenems and thanks to its good oral bioavailability, it is very useful in the treatment of community-acquired infections [22,24,26,28,33]. This is why, after its marketing, faropenem may be indicated in the treatment of communityacquired infections, especially acute bacterial sinusitis, acute exacerbations of chronic bronchitis, community-acquired pneumonia and slight skin and soft tissue infections (including those derived from bites) [17,24,26].…”