Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice.
Ertapenem, a parenteral broad-spectrum 1-beta-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 beta-lactamases, including AmpC- and extended-spectrum beta-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 > or = 20 kg/m(2) 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.
Burkhardt
Olaf
O
Department of Pulmonary Medicine, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. burkhardt.olaf@mh-hannover.de
Derendorf
Hartmut
H
Welte
Tobias
T
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy; D016638:Critical Illness; D004347:Drug Interactions; D024881:Drug Resistance, Bacterial; D004716:Endometritis / Q000188:drug therapy; D000077727:Ertapenem; D005260:Female; D006801:Humans; D010538:Peritonitis / Q000188:drug therapy; D011485:Protein Binding; D051437:Renal Insufficiency / Q000378:metabolism; D013530:Surgical Wound Infection / Q000517:prevention & control; D014552:Urinary Tract Infections / Q000188:drug therapy; D047090:beta-Lactams / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem