Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy: a prospective observational trial

Nowak-Kózka, Ilona; Polok, Kamil; Górka, Jacek; Fronczek, Jakub; Gielicz, Anna; Seczyńska, Bożena; Czuczwar, Mirosław; Kudliński, Bartosz; Szczeklik, Wojciech

doi:10.1007/s43440-019-00056-3

Cited by 6 publications

(14 citation statements)

References 25 publications

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“…Our model suggests that the use of standard zero antibiotic concentration dialysate is associated with greater than 30% decrease in meropenem concentration during the procedure, leading to end concentration of 10 mg/L after dialysis, which has been shown to be not effective against the most common bacteria in ICU worldwide 29 . This has been already well demonstrated in previous trials, leading to recommendation to increase the dose of systemically administrated drug 31 . However, an increased intravenous antibiotic dose results in particularly enlarged risk of dose-related side effects as well as even higher concentration gradient of the drug between blood and dialysate.…”

Section: Discussionsupporting

confidence: 57%

Conceptual model of adding antibiotics to dialysate fluid during renal replacement therapy

Bartuseviciene

Vicka

Vickienė

et al. 2021

Sci Rep

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Studies have shown significant variability in antibiotic trough concentrations in critically ill patients receiving renal replacement therapy (RRT). The purpose of this study was to assess whether adding beta-lactam antibiotics to dialysate solution can maintain stable antibiotic concentrations during RRT in experimental conditions. A single compartment model reflecting the patient was constructed and connected to the RRT machine. Dialysate fluid was prepared in three different concentrations of meropenem (0 mg/L; 16 mg/L; 64 mg/L). For each dialysate concentration various combinations of dialysate and blood flow rates were tested by taking different samples. Meropenem concentration in all samples was calculated using spectrophotometry method. Constructed experimental model results suggest that decrease in blood meropenem concentration can be up to 35.6%. Moreover, experimental data showed that antibiotic loss during RRT can be minimized and stable plasma antibiotic concentration can be achieved with the use of a 16 mg/L Meropenem dialysate solution. Furthermore, increasing meropenem concentration up to 64 mg/L is associated with an increase antibiotic concentration up to 18.7–78.8%. Administration of antibiotics to dialysate solutions may be an effective method of ensuring a constant concentration of antibiotics in the blood of critically ill patients receiving RRT.

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Section: Discussionsupporting

confidence: 57%

Conceptual model of adding antibiotics to dialysate fluid during renal replacement therapy

Bartuseviciene

Vicka

Vickienė

et al. 2021

Sci Rep

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“…Meropenem is eliminated by the kidney. CRRT including CVVH (Isla et al, 2008;Bilgrami et al, 2010;Seyler et al, 2011;Beumier et al, 2014;Sime et al, 2018a;Onichimowski et al, 2020b), CVVHDF (Isla et al, 2008;Seyler et al, 2011;Beumier et al, 2014;Varghese et al, 2015), and CVVHD (Afshartous et al, 2014;Kawano et al, 2015;Shaw and Mueller, 2017;Nowak-Kozka et al, 2020;Onichimowski et al, 2020b) could eliminate meropenem. A wide range of meropenem dose regimens from 0.25g q24h to 2 g q8h have been shown to be effective and were recommended for CRRT with diverse effluent flow rates (Kawano et al, 2015;Grensemann et al, 2020).…”

Section: Meropenemmentioning

confidence: 99%

“…Additionally, increased total clearance of meropenem was observed in patients with higher creatinine clearance (Isla et al, 2005), residual renal function should also be taken into consideration when adjusting the meropenem dose during CRRT (Ulldemolins et al, 2015). Continuous infusion of meropenem seems to be an effective method to improve the clinical efficacy for patients with less susceptible pathogen infections or augmented renal clearance during CRRT (Langgartner et al, 2008;Burger et al, 2018;Nowak-Kozka et al, 2020). Dose regimens should be adjusted according to different effluent flow rates and MICs of pathogens.…”

Section: Meropenemmentioning

confidence: 99%

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

Xia

et al. 2020

Front. Pharmacol.

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Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review:

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“…All included studies were published from June 22, 1998, through January 4, 2020. The key characteristics of the included studies were illustrated in Table 1[5–7, 9, 11–22, 27–31].…”

Section: Resultsmentioning

confidence: 99%

Optimal Meropenem Dosing Regimens in Patients Undergoing Continuous Renal Replacement Therapy: Systematic Review and Monte Carlo Simulations

Charoensareerat¹,

Chaijamorn²,

Kerdnimith³

et al. 2023

Blood Purif

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Introduction: The optimal meropenem dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) based on pharmacokinetic and pharmacodynamic (PD) concepts are not well established. This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving CRRT and (2) to define the optimal meropenem dosing regimens in these populations via Monte Carlo simulations. Methods: We used Medical Subject Headings “meropenem,” “continuous renal replacement therapy,” and “pharmacokinetics” or related terms to identify studies for systematic review. A one-compartment pharmacokinetic model was conducted to predict meropenem levels for the initial 48 h of therapy. The PD targets were 40% of free drug above a threshold of 1 times the minimum inhibitory concentration (MIC) (40% fT > MIC), 4 times the MIC (40% fT > 4MIC), and an additional target of free drug level above 1 times MIC 100% of the time (fT > MIC). The dose that achieved at least 90% of the probability of target attainment (PTA) was defined as an optimal dose. Results: Twenty-one articles were included for our systematic review. The necessary pharmacokinetic parameters such as volume of distribution and CRRT clearance were cited in 90.5 and 71.4% of articles, respectively. None of the published studies reported completed necessary parameters. A regimen of 750 mg q 8 h was found to be the optimal dose for pre-dilution continuous venovenous hemofiltration and continuous venovenous hemodialysis modality using two effluent rates (25 and 35 mL/kg/h) which achieved the PD target of 40% fT > 4MIC. Conclusion: None of the published studies showed the necessary pharmacokinetic parameters. PD target significantly contributed to meropenem dosage regimens in these patients. Differing effluent rates and types of CRRT shared similar dosing regimens. Clinical validation of the recommendation is suggested.

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Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy: a prospective observational trial

Cited by 6 publications

References 25 publications

Conceptual model of adding antibiotics to dialysate fluid during renal replacement therapy

Conceptual model of adding antibiotics to dialysate fluid during renal replacement therapy

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

Optimal Meropenem Dosing Regimens in Patients Undergoing Continuous Renal Replacement Therapy: Systematic Review and Monte Carlo Simulations

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