title: In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.
abstract: Ertapenem (MK-0826, L-749,345) is a 1-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 < or =1 microg/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 < or =0.5 microg/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 on a provisional NCCLS MIC breakpoint of > or =16 microg/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 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-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.
authors.affiliation: Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, London, United Kingdom. DLivermore@phls.nhs.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: M W
authors.initials: MW
authors.lastname: Carter
authors.forename: S
authors.initials: S
authors.lastname: Bagel
authors.forename: B
authors.initials: B
authors.lastname: Wiedemann
authors.forename: F
authors.initials: F
authors.lastname: Baquero
authors.forename: E
authors.initials: E
authors.lastname: Loza
authors.forename: H P
authors.initials: HP
authors.lastname: Endtz
authors.forename: N
authors.initials: N
authors.lastname: van Den Braak
authors.forename: C J
authors.initials: CJ
authors.lastname: Fernandes
authors.forename: L
authors.initials: L
authors.lastname: Fernandes
authors.forename: N
authors.initials: N
authors.lastname: Frimodt-Moller
authors.forename: L S
authors.initials: LS
authors.lastname: Rasmussen
authors.forename: H
authors.initials: H
authors.lastname: Giamarellou
authors.forename: E
authors.initials: E
authors.lastname: Giamarellos-Bourboulis
authors.forename: V
authors.initials: V
authors.lastname: Jarlier
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.forename: C E
authors.initials: CE
authors.lastname: Nord
authors.forename: M J
authors.initials: MJ
authors.lastname: Struelens
authors.forename: C
authors.initials: C
authors.lastname: Nonhoff
authors.forename: J
authors.initials: J
authors.lastname: Turnidge
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: R
authors.initials: R
authors.lastname: Zbinden
authors.forename: S
authors.initials: S
authors.lastname: Pfister
authors.forename: L
authors.initials: L
authors.lastname: Mixson
authors.forename: D L
authors.initials: DL
authors.lastname: Shungu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001315:Australia; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D015780:Carbapenems / Q000494:pharmacology*; D005060:Europe; D008826:Microbial Sensitivity Tests; D011786:Quality Control
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; C108047:L 749345