In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.
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.
Livermore
D M
DM
Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, London, United Kingdom. DLivermore@phls.nhs.uk
Carter
M W
MW
Bagel
S
S
Wiedemann
B
B
Baquero
F
F
Loza
E
E
Endtz
H P
HP
van Den Braak
N
N
Fernandes
C J
CJ
Fernandes
L
L
Frimodt-Moller
N
N
Rasmussen
L S
LS
Giamarellou
H
H
Giamarellos-Bourboulis
E
E
Jarlier
V
V
Nguyen
J
J
Nord
C E
CE
Struelens
M J
MJ
Nonhoff
C
C
Turnidge
J
J
Bell
J
J
Zbinden
R
R
Pfister
S
S
Mixson
L
L
Shungu
D L
DL
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
D000900:Anti-Bacterial Agents; D015780:Carbapenems; C108047:L 749345