Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i>
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 si...
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/9/785 |
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| author | Pier Giorgio Cojutti Anna Candoni Davide Lazzarotto Carla Filì Maria Zannier Renato Fanin Federico Pea |
| author_facet | Pier Giorgio Cojutti Anna Candoni Davide Lazzarotto Carla Filì Maria Zannier Renato Fanin Federico Pea |
| author_sort | Pier Giorgio Cojutti |
| collection | DOAJ |
| description | 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 <i>P. aeruginosa.</i> 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 <i>P. aeruginosa</i> were assessed as well. PTAs and CFRs ≥ 90% were considered optimal. A total of 61 patients with 178 meropenem Css were included. Creatinine clearance (CL<sub>CR</sub>) 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 <i>P. aeruginosa</i> at Css/MIC ≥ 1. When dealing against <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> among FN patients with hematologic malignancies having different degree of renal function. |
| first_indexed | 2024-03-10T17:11:08Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:11:08Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj.art-7e58d14036bf416cb78e292f25d402042023-11-20T10:39:47ZengMDPI AGPharmaceutics1999-49232020-08-0112978510.3390/pharmaceutics12090785Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i>Pier Giorgio Cojutti0Anna Candoni1Davide Lazzarotto2Carla Filì3Maria Zannier4Renato Fanin5Federico Pea6Department of Medicine, University of Udine, 33100 Udine, ItalyDivision of Haematology, Santa Maria della Misericordia University-Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, ItalyDivision of Haematology, Santa Maria della Misericordia University-Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, ItalyDivision of Haematology, Santa Maria della Misericordia University-Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, ItalyDivision of Haematology, Santa Maria della Misericordia University-Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyA 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 <i>P. aeruginosa.</i> 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 <i>P. aeruginosa</i> were assessed as well. PTAs and CFRs ≥ 90% were considered optimal. A total of 61 patients with 178 meropenem Css were included. Creatinine clearance (CL<sub>CR</sub>) 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 <i>P. aeruginosa</i> at Css/MIC ≥ 1. When dealing against <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> among FN patients with hematologic malignancies having different degree of renal function.https://www.mdpi.com/1999-4923/12/9/785continuous-infusion meropenempatients with hematologic malignanciespopulation pharmacokinetics |
| spellingShingle | Pier Giorgio Cojutti Anna Candoni Davide Lazzarotto Carla Filì Maria Zannier Renato Fanin Federico Pea Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> Pharmaceutics continuous-infusion meropenem patients with hematologic malignancies population pharmacokinetics |
| title | Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> |
| title_full | Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> |
| title_fullStr | Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> |
| title_full_unstemmed | Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> |
| title_short | Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and <i>P. aeruginosa</i> |
| title_sort | population pharmacokinetics of continuous infusion meropenem in febrile neutropenic patients with hematologic malignancies dosing strategies for optimizing empirical treatment against enterobacterales and i p aeruginosa i |
| topic | continuous-infusion meropenem patients with hematologic malignancies population pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/12/9/785 |
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