title: In vitro activity and killing effect of DX-8739, a new carbapenem, compared with those of meropenem and imipenem against multiresistant Pseudomonas aeruginosa.
abstract: DX-8739 is a new dehydropeptidase I-stable carbapenem. In order to evaluate its activity in comparison with those of meropenem and imipenem, 147 multiresistant Pseudomonas aeruginosa isolates acquired nosocomially were simultaneously exposed to the actions of the three carbapenems in vitro, whereas to compare their killing effects on 14 strains, 56 killing curve studies were performed. Overall DX-8739 was found to possess inhibitory activity as well as bactericidal activity statistically superior to those of meropenem and imipenem. At a concentration of 4 micrograms/ml, 106 strains (72.1%) were found to be imipenem resistant; 33 and 27.4% of these strains were inhibited by DX-8739 and meropenem, respectively, a statistically significant difference (P < 0.05). DX-8739 was also shown to possess intrinsic activity in vitro superior to those of meropenem and imipenem against the imipenem-susceptible population of strains. However, no statistically significant difference regarding the comparative killing activities of the three studied carbapenems was observed. Following exposure to carbapenem for 24 h, 33.3, 44.4, and 70% of the strains which survived became resistant to DX-8739, meropenem, and imipenem, respectively. The reported results demonstrate the significant activity of DX-8739 against multiresistant P. aeruginosa strains acquired nosocomially. The mechanism of action of DX-8739 on P. aeruginosa is unknown, and various hypotheses that might explain its in vitro superiority over meropenem and imipenem are proposed.
authors.affiliation: 1st Department of Propedeutic Medicine, University of Athens Medical School, Greece.
authors.forename: E J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: P
authors.initials: P
authors.lastname: Grecka
authors.forename: H
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D015378:Imipenem / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013845:Thienamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; C094221:DX 8739; D013845:Thienamycins; D015378:Imipenem; D000077731:Meropenem