Mechanisms and clinical relevance of antagonism between beta-lactam antibiotics

The author discussed the problem of antagonism between combined antibiotics. Several examples of antagonistic combinations between cefoxitin plus moxalactam, or carbenicillin were cited in the literature. This phenomenon may occur especially with Enterobacter spp., Pseudomonas aeruginosa, Citrobacter spp. and Serratia marcescens: in these species induction of chromosomally mediated beta-lactamase by certain potent inducers such as cefoxitin has been suggested as the main mechanism of antagonism. Competition for binding sites (PBPs) or diminished permeability that alter susceptibility to beta-lactams, may be less likely acceptable hypotheses for double beta-lactam combination antagonism. These in vitro interactions may have clinical relevance; however even if studies in animal models showed a few examples of in vivo antagonism, the actual clinical significance of interactions between beta-lactams requires further thorough controlled clinical studies.