Chemical and Microbiologic Aspects of Penems, a Distinct Class of β-Lactams: Focus on Faropenem

Jeremy M. T. Hamilton-Miller, D.Sc., FRCPath


Pharmacotherapy. 2003;23(11) 

In This Article

Abstract and Introduction

Many β-lactam antimicrobials were developed between the 1960s and 1980s, with continuing development driven by the emergence of microbial resistance. Penems form a discrete class of β-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems). The chemistry and microbiology of the representative penems MEN 10700, ritipenem, CGP 31608, sulopenem, BRL 42715, and faropenem are reviewed. Particular emphasis is placed on faropenem, which is in late clinical development.

β-lactam antimicrobials are widely recognized for their efficacy and low toxicity and form the cornerstone of therapy for the treatment of infections caused by gram-positive and gram-negative bacteria. However, extensive use of β-lactams during the past 50 years has resulted in the development of microbial resistance to these agents among clinically important bacteria.[1] This resistance commonly takes the form of β-lactamase production or alterations in penicillin-binding proteins (PBPs).[1,2] Such mechanisms have reduced the clinical utility of frequently prescribed β-lactams such as amoxicillin, amoxicillin plus clavulanate (a β-lactamase inhibitor), and cephalosporins. The issue of resistance continues to drive the search for new compounds with increased stability and efficacy against resistant pathogens.

The options for derivatizing naturally occurring β-lactams have been explored to near exhaustion, with attention focused on synthetic β-lactams, the penems, in the search for novel compounds.[3] Designed and synthesized in 1977, these molecules are derived from the core structures of penicillin and cephalosporin molecules.[4] They offer good β-lactamase stability and in vitro activity against a broad range of pathogenic bacteria.