Disease relevance of Ertapenem

• Activity of ertapenem (MK-0826) versus Enterobacteriaceae with potent beta-lactamases [1].
• Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus pneumoniae in a murine neutropenic thigh infection model [2].
• Role of beta-lactamases and porins in resistance to ertapenem and other beta-lactams in Klebsiella pneumoniae [3].
• Ertapenem has a role in the treatment of CAP associated with typical respiratory pathogens and is of particular value in the treatment of polymicrobial infections (such as CIAI, CSSSI, CUTI and acute pelvic infections), especially where Enterobacteriaceae and anaerobic bacteria are involved [4].
• Outer membrane protein changes and efflux pump expression together may confer resistance to ertapenem in Enterobacter cloacae [5].

High impact information on Ertapenem

• However, for isolates with raised ertapenem MICs of >/=2 mug/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC [6].
• Diminished expression of oprD was present in all imipenem- and meropenem-resistant isolates but was not required for ertapenem resistance [7].
• Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults [8].
• Linezolid in combination with ertapenem showed in vitro synergy against methicillin-resistant Staphylococcus aureus strains [9].
• Little is known of the effects of obesity on ertapenem drug disposition and pharmacodynamics [8].

Chemical compound and disease context of Ertapenem

• Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-{beta}-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model [6].
• MICs of ertapenem for AmpC-derepressed mutant Enterobacteriaceae were 0.015 to 0.5 microg/ml, whereas imipenem MICs were 0.25 to 1 microg/ml and those of cefepime were 0.5 to 4 microg/ml, and resistance to ceftazidime and piperacillin-tazobactam was generalized [1].
• Susceptibilities of Propionibacterium acnes Ophthalmic Isolates to Ertapenem, Meropenem, and Cefepime [10].
• OBJECTIVES: Assessment of the activity of three beta-lactams [ertapenem (a carbapenem with a prolonged half-life), meropenem and ampicillin] against intraphagocytic Listeria monocytogenes and Staphylococcus aureus [11].
• This investigation tested the mutation prevention concentration (MPC) concept using imipenem, meropenem, ceftriaxone, and ertapenem against three strains of Streptococcus pneumoniae (PCN MIC = 0.012, 1, 8 mg/L, respectively) [12].

Biological context of Ertapenem

• The pharmacokinetics of ertapenem in elderly subjects, while slightly different from those in young adults, do not require a dosage adjustment for elderly patients [13].
• The effect of protein binding on the antimicrobial activity of ertapenem was evaluated using the bacterial kill rate and concentration-response studies [14].
• The kinetics for other beta-lactams were similar to those of ertapenem [15].
• A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers [16].
• Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 +/- 0.17 and 0.59 +/- 0.22 log(10) CFU/ml x h, respectively, in the viable cell counts in the cerebrospinal fluid [17].

Anatomical context of Ertapenem

• The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively [17].
• Isolates from a variety of infections (intra-abdominal infections, skin/soft-tissue infections, community-acquired pneumonia, pelvic infections and urinary tract infections) are inhibited by ertapenem [18].
• RESULTS: Mean+/-SD ertapenem tissue concentration (mg/kg) was 16.0+/-8.8 in the gall bladder, 12.1+/-5.3 in the colon, 7.0+/-5.7 in the small bowel, 4.5+/-2.3 in the liver and 3.4+/-2.9 in the pancreas [19].
• Mean peak concentrations of free, protein-unbound ertapenem in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were much lower (C(max) = 6.7 +/- 4.1 and 4.0 +/- 1.6 mg/L, respectively) [20].
• Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis [20].

Associations of Ertapenem with other chemical compounds

• At the primary efficacy endpoint 5 to 9 days after treatment, 91.8% of patients who received ertapenem and 93.0% of those who received ceftriaxone had a favorable microbiological response (95% confidence interval for the difference, adjusting for strata, -7.6 to 5.1%), indicating that outcomes in the two treatment groups were equivalent [21].
• The killing kinetics of clarithromycin were slower than those of ertapenem and other agents, with clarithromycin at two times the MIC having bactericidal activity against seven of eight macrolide-susceptible strains after 24 h [22].
• CONCLUSIONS: Whilst ertapenem can select for P. aeruginosa mutants with cross-resistance to imipenem and ertapenem in vitro, this selectivity should be minimal under clinical conditions [23].
• Methicillin-susceptible S. aureus and K. pneumoniae, including extended-spectrum beta-lactamase-producing strains, were 100% susceptible to ertapenem [24].
• Ertapenem: a new opportunity for outpatient parenteral antimicrobial therapy [25].

Gene context of Ertapenem

• The IMP-1 metallo-beta-lactamase conferred substantial ertapenem resistance (MIC, 128 microg/ml) in a porin-deficient Klebsiella pneumoniae strain, whereas a MIC of 6 microg/ml was recorded for its porin-expressing revertant [1].
• In a three-period crossover study (Part A), 26 healthy subjects received single doses of ertapenem administered i.m., i.v. infused over 30 min, and i.v. infused over 120 min [26].
• In vitro susceptibility of ertapenem by BSAC standardized methodology [27].
• A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor [28].
• Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome P450 enzymes; significant drug interactions between ertapenem and drugs handled by these systems are not expected [29].

Analytical, diagnostic and therapeutic context of Ertapenem

• The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [16].
• 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 [30].
• The results suggest that the standard 1-g ertapenem dose may not provide adequate drug exposure for any body mass index classification for MICs in excess of 0.25 to 0.5 mug/ml [8].
• In vitro activity of ertapenem against bacteraemic pneumococci: report of a French multicentre study including 339 strains [31].
• The present microdialysis study was conducted to measure free, protein-unbound ertapenem concentrations in muscle and subcutaneous tissue [20].

References