Comparative in vitro activities of L-695,256, a novel carbapenem, against gram-positive bacteria

Abstract

The in vitro activity of a prototype 2-aryl carbapenem, L-695,256, against gram-positive bacteria was examined. All streptococci and oxacillin-susceptible and -resistant staphylococci were inhibited at concentrations of Յ0.125, Յ0.125, and 4 g/ml, respectively. The activity of L-695,256 was superior to that of imipenem against other organisms intrinsically resistant to ␤-lactams.The introduction of imipenem into clinical practice represented a major advance. Its broad antibacterial spectrum is potentially advantageous for empiric treatment of infections prior to identification of causative organisms and for treatment of polymicrobial infections. In addition, because of resistance to hydrolysis by most clinically important ␤-lactamases and other favorable characteristics, this carbapenem often retains activity against nosocomial isolates of gram-negative bacteria resistant to other ␤-lactam antibiotics (3,4,18). Two notable exceptions to this favorable pattern of activity are methicillinresistant staphylococci and penicillin-resistant enterococci, both of which display reduced susceptibility to imipenem (20). In both instances, resistance to ␤-lactams can be attributed to the presence of penicillin-binding proteins with reduced affinities for these agents (7,8,14,16,22). Neither of the two more recently developed carbapenems, meropenem and biapenem, offers any activity advantage over imipenem against these organisms in particular or against gram-positive bacteria in general (13,20).L-695,256 ( Fig. 1) is one of a series of novel 2-aryl carbapenems selected for evaluation because of its unusually good activity against methicillin-resistant staphylococci (19). This drug binds to PBP 2a of Staphylococcus aureus and to PBP 5 of Enterococcus hirae with substantially greater affinity than comparable ␤-lactams (6, 9). The present study was undertaken to examine the in vitro activity of L-695,256 against a variety of gram-positive bacteria, including strains specifically collected because of their resistance to ␤-lactams or other antibiotics.(This work was presented in part at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, Fla., October 1994 [12].)Most of the organisms included in this study were clinical isolates obtained at Deaconess Hospital and Massachusetts General Hospital, Boston, Mass. Strains of streptococci demonstrating resistance to ␤-lactams and strains of vancomycinresistant enterococci had been referred to our collection from a variety of sources (13,20). L-695,256 and imipenem were provided by Merck, Sharp & Dohme Research Laboratories, Rahway, N.J. Other susceptibility reference powders were gifts from the indicated sources: oxacillin, Bristol-Myers Squibb Co., Syracuse, N.Y.; clindamycin, Upjohn Co., Kalamazoo, Mich.; erythromycin and vancomycin, Eli Lilly & Co., Indianapolis, Ind.; and teicoplanin, Marion Merrell Dow, Inc., Cincinnati, Ohio.Antimicrobial susceptibility was determined by an agar dilution technique as previously described (13). Mueller-Hinton II agar ...

In Vitro and In Vivo Antibacterial Activities of SM-216601, a New Broad-Spectrum Parenteral Carbapenem

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In Vitro and In Vivo Activities of Novel 2-(Thiazol-2-ylthio)-1β-Methylcarbapenems with Potent Activities against Multiresistant Gram-Positive Bacteria

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Antibiotic resistance: a current perspective

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