Carbapenems are β-lactam drugs that are structurally different from penicillins and cephalosporins. For example, imipenem (N-formimidoylthienamycin), a commonly used carbapenem, has a methylene group in the ring in place of the sulfur (Figure 1). Imipenem has one of the widest spectrums of activity of the β-lactam drugs. It has excellent bactericidal activity against many gram-positive, gram negative, and anaerobic bacteria (Table 1). It is effective against most gram-positive cocci (e.g., staphylococci and streptococci), most gram-negative cocci (e.g., Neisseria meningitidis), many gram-negative rods (e.g., Pseudomonas, Haemophilus, and members of the family Enterobacteriaceae such as E. coli), and various anaerobes (e.g., Bacteroides and Clostridium).
Table1. Clinical Activity of Selected Carbapenems
Imipenem is especially useful in treating infections caused by gram-negative rods that produce extended-spectrum β-lactamases that make them resistant to all penicillins and cephalosporins. Carbapenems are often the “drugs of last resort” against bacteria resistant to multiple antibiotics and are thus reserved for hospital settings.
Imipenem is prescribed in combination with cilastatin, which is an inhibitor of dehydropeptidase, a kidney enzyme that inactivates imipenem. Other carbapenems, such as ertapenem and meropenem, are not inactivated by dehydropeptidase and are not prescribed in combination with cilastatin.
Most β-lactamases can’t inactivate imipenem; however, carbapenemases produced by K. pneumoniae that degrade imipenem and other carbapenems have emerged. To address the problem of carbapenemase-producing gram-negative rods, the FDA approved a combination of meropenem–vaborbactam (Vabomere) for the treatment of complicated UTIs caused by E. coli, K. pneumoniae, and others. Vaborbactam is a carbapenemase/β-lactamase inhibitor.
