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Carbapenem: Wikis

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Structure of carbapenem backbone

Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases. Carbapenem antibiotics were originally developed from thienamycin, a naturally-derived product of Streptomyces cattleya.[1]

Contents

Examples

The following drugs belong to the carbapenem class:

  • Imipenem (often given as part of Imipenem/cilastatin)
    • Imipenem can be hydrolysed in the mammalian kidney by a dihydropeptidase enzyme, and so is given with a dehydropeptidase inhibitor, cilastatin
  • Meropenem
  • Ertapenem
  • Doripenem
  • Panipenem/betamipron
  • Biapenem
  • PZ-601
    • PZ-601 is a carbapenem antibiotic currently being tested as having a broad spectrum of activity including strains resistant to other carbapenems.

Faropenem is closely related, but it is a penem, not a carbapenem.[2]

Uses

These agents have the broadest antibacterial spectrum compared to other beta-lactam classes such as penicillins and cephalosporins. Additionally they are generally resistant to the typical bacterial beta-lactamase enzymes which are one of the principal resistance mechanisms of bacteria. They are active against both Gram positive, gram negative bacteria, and anaerobes, with the exception of intracellular bacteria (atypicals), such as the Chlamydiae. Carbapenems also are thus-far the only beta-lactams capable of inhibiting L,D-Transpeptidases [3].

Structure

The carbapenems are structurally very similar to the penicillins, but the sulfur atom in position 1 of the structure has been replaced with a carbon atom, and hence the name of the group, the carbapenems.

Biosynthesis

The carbapenams are thought to share their early biosynthetic steps in which the core ring system is formed. Malonyl-CoA is condensed with glutamate 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 they have generally poor oral bioavailability, they are administered intravenously in hospital settings for more serious infections. However, research is underway to develop an effective oral carbapenem.[4]

References

  1. ^ Birnbaum J, Kahan FM, Kropp H, MacDonald JS (1985). "Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin". Am. J. Med. 78 (6A): 3–21. doi:10.1016/0002-9343(85)90097-X. PMID 3859213. 
  2. ^ "Medscape.com". http://www.medscape.com/viewarticle/464632_2. 
  3. ^ Mainardi, Jean-Luc et al.: "Evolution of Peptidoglycan Biosynthesis under the Selective Pressure of Antibiotics in Gram-Positive Bacteria" Federation of European Microbiological Societies, 2008.
  4. ^ Kumagai T, Tamai S, Abe T, Hikda M (2002). "Current Status of Oral Carbapenem Development". Current Medicinal Chemistry -Anti-Infective Agents 1: 1–14. doi:10.2174/1568012023355018. http://www.ingentaconnect.com/content/ben/cmcaia/2002/00000001/00000001/art00002. 

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