Ertapenem Pharmacokinetics and Pharmacodynamics during Continuous Ambulatory Peritoneal Dialysis

Cardone, Katie E.; Grabe, Darren W.; Kulawy, Robert; Daoui, Rachid; Roglieri, Joseph; Meola, Shari; Drusano, George L.; Lodise, Thomas P.

doi:10.1128/aac.05515-11

Cited by 14 publications

(9 citation statements)

References 25 publications

(35 reference statements)

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“…Aside from the work described herein, to our knowledge, only three other groups previously utilized nonlinear functions to characterize ertapenem protein binding when conducting ertapenem PK-PD target attainment analyses (30)(31)(32). Additional strengths of these analyses were the utilization of a population PK model which included formally selected covariates and the evaluation of effect-site exposures for patients with HABP/VABP (i.e., ELF AUC values), two considerations which appear to be absent in the available literature describing ertapenem PK-PD target attainment analyses (30)(31)(32)(33)(34)(35)(36)(37). The former consideration allowed for the evaluation of simulated exposures which accounted for the impact of body size and renal function on ertapenem PK.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Bader

Lakota

Dale

et al. 2019

Antimicrob Agents Chemother

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Ertapenem provides activity against many pathogens commonly associated with hospital-acquired and ventilator-associated bacterial pneumoniae (HABP and VABP, respectively), including methicillin-susceptible Staphylococcus aureus and numerous Gram-negative pathogens with one major gap in coverage, Pseudomonas aeruginosa. Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were conducted to evaluate ertapenem against the most prevalent Enterobacteriaceae causing HABP/VABP. The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against P. aeruginosa. A previously developed population pharmacokinetic model, a total-drug epithelial lining fluid (ELF) to free-drug serum penetration ratio, contemporary in vitro surveillance data for ertapenem against Enterobacteriaceae, and percentage of the dosing interval for which drug concentrations exceed the MIC value (%TϾMIC) targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem regimens administered over short or prolonged durations of infusion. Overall total-drug ELF percent probabilities of PK-PD target attainment based on a %TϾMIC target of 35% among simulated patients with HABP/VABP arising from Enterobacteriaceae based on pathogen prevalence data for nosocomial pneumonia ranged from 89.1 to 92.7% for all five ertapenem regimens evaluated. Total-drug ELF percent probabilities of PK-PD target attainment ranged from 99.8 to 100%, 97.9 to 100%, 10.6 to 74.1%, and 0 to 1.50% at MIC values of 0.06, 0.12, 1, and 4 g/ml, respectively (MIC 90 values for Escherichia coli, Serratia marcescens, Enterobacter species, and Klebsiella pneumoniae, respectively). Results of these analyses provide support for the evaluation of ertapenem in combination with murepavadin for the treatment of patients with HABP/ VABP.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Bader

Lakota

Dale

et al. 2019

Antimicrob Agents Chemother

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“…Ertapenem is eliminated primarily by the kidney (∼80%). The recommended dose in adult patients with CrCl <30 mL/min/1.73 m 2 is 0.5 g every 24 h. There are no data to recommend ertapenem dosage in PD patients, but 500 mg IV seemed to achieve adequate drug exposure in serum and the peritoneal cavity [ 67 ]. Ertapenem is unstable in dextrose solution, hence should not be administered intraperitoneally [ 68 ].…”

Section: Carbapenemmentioning

confidence: 99%

Newer antibiotics for the treatment of peritoneal dialysis-related peritonitis

et al. 2016

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Peritonitis is a debilitating infectious complication of peritoneal dialysis (PD). Drug-resistant bacterial peritonitis typically has a lower response rate to antibiotics. In the past 15 years, newer antibiotics with activities against drug-resistant Gram-positive bacteria have been developed. In most circumstances, peritonitis due to methicillin-resistant staphylococci responds to vancomycin. If vancomycin cannot be used due to allergy and/or non-susceptibility, there is increasing evidence that linezolid and daptomycin are the drugs of choice. It is reasonable to start linezolid orally or intravenously, but subsequent dose reduction may be necessary in case of myelosuppression. Daptomycin can be given intravenously or intraperitoneally and has excellent anti-biofilm activity. Other treatment options for drug-resistant Gram-positive bacterial peritonitis include teicoplanin, tigecycline and quinupristin/dalfopristin. Teicoplanin is not available in some countries (e.g. the USA). Tigecycline can only be given intravenously. Quinupristin/dalfopristin is ineffective against Enterococcus faecalis and there is only low-quality evidence to support its efficacy in the treatment of peritonitis. Effective newer antibiotics against drug-resistant Gram-negative bacteria are lacking. Polymyxins can be considered, but evidence on its efficacy is limited. In this review, we will discuss the potential use of newer antibiotics in the treatment of drug-resistant bacterial peritonitis in PD patients.

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“…All pharmacokinetic calculations were performed using the MW/Pharm software package (version 3.82; Mediware, Zuidhorn, The Netherlands). On the basis of the findings presented in previous reports and the findings of recent pharmacokinetic studies of ertapenem (10)(11)(12)(13)(14)(15)(16)(17)(23)(24)(25), concentration-time curves were evaluated in one-compartment and two-compartment models. The final model was selected on the basis of the AIC (27).…”

Section: Methodsmentioning

confidence: 99%

“…The pharmacokinetics of ertapenem have typically been studied in healthy volunteers (9), people with obesity (10,11), patients with renal failure (12)(13)(14), and critically ill patients with various pathologies (15)(16)(17). Lower levels of drug exposure were observed in obese individuals (11), and an increase in the dosing interval was needed in patients with renal insufficiency with an estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m 2 (13), suggesting that the optimal dose of ertapenem is different in patients with different health conditions.…”

mentioning

confidence: 99%

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

Rijn

Zuur

Altena

et al. 2017

Antimicrob Agents Chemother

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Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% T MIC ). To assess the 40% T MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentrationtime curve from 0 to 24 h [AUC 0 -24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation (n ϭ 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% T MIC with the free fraction (f 40% T MIC ) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) in MDR-TB patients by 6.8% (range, Ϫ17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h (r 2 ϭ 0.78, mean prediction error ϭ Ϫ0.33%, root mean square error ϭ 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, Ϫ15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% T MIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR-TB patients.

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Ertapenem Pharmacokinetics and Pharmacodynamics during Continuous Ambulatory Peritoneal Dialysis

Cited by 14 publications

References 25 publications

Pharmacokinetic-Pharmacodynamic Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Pharmacokinetic-Pharmacodynamic Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Newer antibiotics for the treatment of peritoneal dialysis-related peritonitis

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

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