High-performance liquid chromatographic assay for meropenem in serum

Elkhaïli, H.; Niedergang, S; Pompei, D.; Linger, L.; Levêque, Dominique; Jehl, F.

doi:10.1016/s0378-4347(96)00205-8

Cited by 65 publications

(43 citation statements)

References 12 publications

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“…Protein binding was applied by multiplying each concentration by 0.97 over the 24-hour period. The simulated peak concentration for each dose at 3, 11, and 19 h was 38.4 g/ml, and the trough at 0, 8,16, and 24 h was 3.04 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

Bulik

Christensen

et al. 2010

Antimicrob Agents Chemother

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We have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosa with MICs of <16 g/ml. The objective of this experiment was to compare the efficacy of this high-dose, prolonged-infusion regimen against carbapenemase-producing Klebsiella pneumoniae isolates with the efficacy against P. aeruginosa isolates having similar meropenem MICs. An in vitro pharmacodynamic model was used to simulate human serum concentrations. Eleven genotypically confirmed K. pneumoniae carbapenemase (KPC)-producing isolates and six clinical P. aeruginosa isolates were tested for 24 h, and time-kill curves were constructed. High-performance liquid chromatography (HPLC) was used to verify meropenem concentrations in each experiment. Meropenem achieved a rapid >3 log CFU reduction against all KPC isolates within 6 h, followed by regrowth in all but two isolates. The targeted %fT>MIC (percent time that free drug concentrations remain above the MIC) exposure was achieved against both of these KPC isolates (100% fT>MIC versus MIC ‫؍‬ 2 g/ml, 75% fT>MIC versus MIC ‫؍‬ 8 g/ml). Against KPC isolates with MICs of 8 and 16 g/ml that did regrow, actual meropenem exposures were significantly lower than targeted due to rapid in vitro hydrolysis, whereby targeted %fT>MIC was reduced with each subsequent dosing. In contrast, a >3 log CFU reduction was maintained over 24 h for all Pseudomonas isolates with meropenem MICs of 8 and 16 g/ml. Although KPC and P. aeruginosa isolates may share similar meropenem MICs, the differing resistance mechanisms produce discordant responses to a high-dose, prolonged infusion of meropenem. Thus, predicting the efficacy of an antimicrobial regimen based on MIC may not be a valid assumption for KPC-producing organisms.

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Section: Methodsmentioning

confidence: 99%

Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

Bulik

Christensen

et al. 2010

Antimicrob Agents Chemother

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“…Meropenem serum samples were analyzed by a validated high-performance liquid chromatography (HPLC) method as previously described (9). The meropenem HPLC assay was linear (r ϭ 0.998) over a concentration range of 0.25 to 40.0 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model

DeRyke¹,

Banevicius²,

Fan

et al. 2007

Antimicrob Agents Chemother

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The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-␤-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10 5 inoculum. Three isolates were examined at a high 10 7 inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (g/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs were <1.5 g/ml for ertapenem (<0.5 g/ml for meropenem), similar reductions in CFU (Ϸ 2-log kill) were observed for both ertapenem (fT>MIC > 23%) and meropenem (fT>MIC > 75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of >2 g/ml (fT>MIC < 20%), while meropenem displayed antibacterial potency that varied from a static effect to a 1-log bacterial reduction in these isolates (fT>MIC ‫؍‬ 30 to 65%). At a 10 7 inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC ‫؍‬ 20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of >2 g/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.

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“…Meropenem concentrations were measured using a previously validated HPLC procedure [12]. The meropenem assay range of 0.1-50 Ìg/ml was determined to be linear with excellent correlation during consecutive runs used for validation prior to analysis of unknown samples.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of High-Dose Meropenem in Adult Cystic Fibrosis Patients

Bui

Ambrose²,

Nicolau

et al. 2001

Chemotherapy

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Because patients with cystic fibrosis (CF) have pulmonary exacerbations secondary to multi-antibiotic-resistant Gram-negative bacilli, antibiotics, like meropenem, are often utilized. We studied the pharmacokinetics of meropenem (2 g i.v. administered every 8 h in clinically stable CF patients to determine if the recommended maximum doses could sustain adequate concentrations during the dosing interval. These pharmacokinetic data were similar to those obtained in non-CF populations. Using this regimen, concentrations of meropenem exceed the susceptibility breakpoint (4 µg/ml) for 50% of the dosing interval, and therefore provide optimization of the pharmacodynamic profile of the compound.

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High-performance liquid chromatographic assay for meropenem in serum

Cited by 65 publications

References 12 publications

Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model

Pharmacokinetics of High-Dose Meropenem in Adult Cystic Fibrosis Patients

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