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-␤-methyl carbapenem with a long serum half-life. Its in vitro activitywas 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 <1 g/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 <0.5 g/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 >16 g/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 <2 g/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 g/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 g/ml and one required an MIC of 4 g/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 g/ml. These streptococci also had diminished susceptibilities to other ␤-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.

Multicenter Antimicrobial Susceptibility Survey of Gram-Negative Bacteria Isolated from Patients with Community-Acquired Infections in the People's Republic of China

“…These findings are similar to those from European, Australian, and American studies (4,6,7). However, ertapenem was less active against Acinetobacter spp.…”

Ertapenem versus Ceftriaxone Followed by Appropriate Oral Therapy for Treatment of Complicated Urinary Tract Infections in Adults: Results of a Prospective, Randomized, Double-Blind Multicenter Study

“…Several studies have shown that most members of the family Enterobacteriaceae are highly susceptible to ertapenem, including isolates resistant to several other antimicrobial agents (6,9). In this study, members of the family Enterobacteriaceae, all of which were susceptible to ertapenem, accounted for 93.0% of all isolates from microbiologically evaluable patients in both treatment groups.…”

“…Ertapenem (formerly MK-0826; Merck & Co., Inc.) is a once a day parenteral ␤-lactam agent with excellent in vitro activity against many gram-positive and gram-negative aerobes and anaerobes generally associated with community-acquired infections, including most members of the family Enterobacteriaceae, pathogens most commonly responsible for UTIs (6,9). Ertapenem is not indicated for Pseudomonas aeruginosa or enterococci, which are more often associated with nosocomial infections.…”

Ertapenem Pharmacokinetics and Impact on Intestinal Microflora, in Comparison to Those of Ceftriaxone, after Multiple Dosing in Male and Female Volunteers

“…By taking into account the fact that a T Ͼ MIC of 30 to 40% is required for ertapenem and that a T Ͼ MIC of 60 to 70% is required for ceftriaxone and the fact that both antibiotics exhibit free fractions between 5 and 10% in the therapeutic concentration range (6,10), the directly measured concentration of ertapenem at 12 h (11.8 mg/liter) can be compared with the concentration of ceftriaxone at 24 h (10.3 mg/liter). The interpretation of these data in the context of the MICs of ceftriaxone and ertapenem at which 90% of isolates are inhibited, obtained in a large multicenter surveillance study (5), revealed that both antibiotics have comparable pharmacokinetic-pharmacodynamic parameters for Moraxella spp., pneumococci, and Haemophilus influenzae, the most frequent pathogens causing community-acquired pneumonia. The pharmacokinetic-pharmacodynamic parameters for ertapenem were particularly favorable for activity against Staphylococcus aureus, a more frequent cause of pneumonia in elderly people and patients with comorbidities.…”