IN-VITRO ACTIVITY AND KILLING EFFECT OF DX-8739, A NEW CARBAPENEM, COMPARED WITH THOSE OF MEROPENEM AND IMIPENEM AGAINST MULTIRESISTANT PSEUDOMONAS-AERUGINOSA

DX-8739 is a new dehydropeptidase I-stable carbapenem. In order to eva luate its activity in comparison with those of meropenem and imipenem, 147 multiresistant Pseudomonas aeruginosa isolates acquired nosocomia lly were simultaneously exposed to the actions of the three carbapenem s in vitro, whereas to compare their killing effects on 14 strains, 56 killing curve studies were performed. Overall DX-8739 was found to po ssess inhibitory activity as well as bactericidal activity statistical ly superior to those of meropenem and imipenem. At a concentration of 4 mu g/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, r espectively, a statistically significant difference (P < 0.05), DX-873 9 was also shown to possess intrinsic activity in vitro superior to th ose of meropenem and imipenem against the imipenem-susceptible populat ion of strains, However, no statistically significant difference regar ding the comparative killing activities of the three studied carbapene ms 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, m eropenem, and imipenem, respectively, The reported results demonstrate the significant activity of DX-8739 against multiresistant P. aerugin osa strains acquired nosocomially, The mechanism of action of DX-8739 on P. aeruginosa. is unknown, and various hypotheses that might explai n its in vitro superiority over meropenem and imipenem are proposed.