Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

Cojutti, Pier Giorgio; Maximova, Natalia; Pea, Federico

doi:10.1128/aac.00787-15

Cited by 18 publications

(18 citation statements)

References 40 publications

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“…A flowchart of study selection for each drug is provided in Figure . A total of 2082 articles were identified and screened, with 130 studies included in the final analysis . Some studies provided PK parameters for two drugs (e.g.…”

Section: Resultsmentioning

confidence: 99%

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Lonsdale

Baker

Kipper

et al. 2018

Brit J Clinical Pharma

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Section: Resultsmentioning

confidence: 99%

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Lonsdale

Baker

Kipper

et al. 2018

Brit J Clinical Pharma

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“…Peripheral blood samples were drawn at each TDM assessment, and meropenem concentrations were analyzed by means of a validated high-performance liquid chromatography (HPLC) method [ 15 ] with some modifications, as previously described [ 13 , 16 ]. Precision and accuracy were assessed by replicate analysis of quality control samples against calibration standards.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and P. aeruginosa

et al. 2020

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A population pharmacokinetic analysis of continuous infusion (CI) meropenem was conducted in a prospective cohort of febrile neutropenic (FN) patients with hematologic malignancies. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed for identifying the most appropriate dosages for empirical treatment against common Enterobacterales and P. aeruginosa. The probability of target attainment (PTA) of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) ratio (Css/MIC) ≥1 and ≥4 at the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint of 2 mg/L were calculated. Cumulative fraction of response (CFR) against Enterobacterales and P. aeruginosa were assessed as well. PTAs and CFRs ≥ 90% were considered optimal. A total of 61 patients with 178 meropenem Css were included. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may grant optimal PTAs of Css/MIC ≥4 at the EUCAST clinical breakpoint. Optimal CFRs may be granted with these dosages against the Enterobacterales at Css/MIC ≥ 4 and against P. aeruginosa at Css/MIC ≥ 1. When dealing against P. aeruginosa at Css/MIC ≥ 4, only a dosage of 1.5 g q6h by CI may grant quasi-optimal CFR (around 80–87%). In conclusion, our findings suggest that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may maximize empirical treatment against Enterobacterales and P. aeruginosa among FN patients with hematologic malignancies having different degree of renal function.

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“…However, the interaction between the PK of carbapenems and body weight is complex, and the accuracy of dosing strategies with hydrophilic carbapenems is challenging when treating severe pneumonia in critically ill patients with high body weight [19]. Under such circumstances, the vigilant use of therapeutic drug monitoring may be helpful in these patients [20].…”

Section: Discussionmentioning

confidence: 99%

Impact of High Body Weight on Mortality in Critically Ill Patients Receiving Meropenem for Pneumonia

Gao

Liang

Peng

2019

Cureus

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Introduction: Body size has a significant impact on pharmacokinetics of antibiotics, and leaving body size out of consideration may increase the probability of therapeutic failure. The objective of this study is to evaluate the impact of high body weight on mortality in critically ill patients who received meropenem for pneumonia. Methods: The electronic medical records of a respiratory intensive care unit (RICU) were retrospectively screened for patients with the first diagnosis of pneumonia and receiving meropenem from 2014 to 2018. Clinical variables and outcome measures were collected in patients who met inclusion criteria. Patients were assigned to quartiles based on body weight (quartile (Q) 1 <52.25 kg; Q2 52.25-65.00 kg; Q3 65.01-72.85; Q4 >72.85 kg). Logistic regression analyses were used to investigate associations between the body weight and mortality. Mortality rates were compared among different body weight quartiles. Results: Of 1,621 patients admitted to the RICU, 146 patients met the inclusion criteria. There was no significant difference in mortality of patients in different body weight quartiles. In subgroup analysis of patients receiving mechanical ventilation, there was an association between body weight and RICU mortality (odds ratio, 2.97 [1.128-7.846]; P=0.027). In Q4, mortality rate of patients who received meropenem 2 g/day was significantly higher than that of patients who received 3 g/day (69.56% vs 35.71%; P=0.047). Conclusions: There was an association between body weight and mortality in patients receiving mechanical ventilation. Compared with low-dose meropenem, high-dose meropenem might decrease mortality rate of critically ill patients with highest body weight.

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Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

Cited by 18 publications

References 40 publications

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and P. aeruginosa

Impact of High Body Weight on Mortality in Critically Ill Patients Receiving Meropenem for Pneumonia

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