In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia

Ertapenem (MK-0826, L-749,345) is a l-beta -methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of less than or equal to1 mug/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained less than or equal to0.5 mug/ml. Acinetobacter spp. and Pseudomonas aeruginosa. were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based an a provisional NCCLS MIC breakpoint of greater than or equal to 16 mug/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising I Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of less than or equal to2 mug/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 mug/ml, Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 mug/ml and one required an MIC of 4 mug/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 mug/ml. These streptococci also had diminished susceptibilities to other p-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.