Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice

Ertapenem, a parenteral broad-spectrum 1-β-methyl-carbapenem, was licensed 5 years ago for clinical practice in the US and Europe. The substance has a good in vitro activity against many common aerobic and anaerobic Gram-positive and -negative bacteria. Its in vitro activity against Enterobacteriaceae carrying plasmid- or chromosomal-mediated β-lactamases, including AmpC- and extended-spectrum β-lactamases, is especially clinically significant. Advantages concerning in vitro activity and low potential for so-called ‘collateral damage’, and development of own resistance during therapy, as shown in several randomized, controlled clinical trials, make ertapenem an excellent treatment choice for complicated aerobic and anaerobic mix infections caused by ertapenem-sensitive bacteria. On the other hand, due to its limited activity against Acinetobacter spp., enterococci and Pseudomonas aeruginosa, it is less suitable for late-onset nosocomial infections. International guidelines recommend the initial empirical use of ertapenem for intra-abdominal infections, skin and skin-structure infections, acute pelvic infections, complicated urinary tract infections and pneumonia (both community-acquired and ‘early-onset’ nosocomial) in a dose of 1.0 g administered once daily. However, recent results from pharmacokinetic/pharmacodynamic modelling studies in critically ill patients with ventilator-associated pneumonia and adipose volunteers with a body mass index of ≥ 20 kg/m² showed that the standard dose of 1.0 g/day may not provide adequate free, protein-unbound drug concentrations in plasma and organ tissues. Therefore, a shortening of the dosage interval or continuous infusion of ertapenem should be considered to ensure optimal free concentrations in these particular populations.