Relationship between continuous infusion meropenem PK/PD target attainment and C‐reactive protein dynamics in onco‐haematologic patients with febrile neutropenia
British Journal of Clinical Pharmacology, vol. 92, pp. 3646–3655
Abstract
AIM: Meropenem is a second-line antimicrobial agent in the treatment of febrile neutropenia in onco-haematological patients. A population pharmacokinetic/pharmacodynamic (PK/PD) analysis for assessing the relationship between meropenem exposure and C-reactive protein (C-RP) over time was conducted. METHODS: . Clinical outcome was assessed at the end of antimicrobial treatment. RESULTS: A total of 141 patients were included in the analysis. A one-compartment model with estimated glomerular filtration rate as a covariate on drug clearance well-described meropenem pharmacokinetics. An indirect turnover maximum inhibition model was used to capture C-RP dynamics. Patients with C-RP Day 4/baseline ratio of <0.4 (fast response), between 0.4 and 0.8 (slow response) and >0.8 (no response) were 8.5%, 15.6% and 75.9%, respectively. Regression analysis showed that patients with fast and slow response patterns were associated with favourable clinical outcomes. Simulations showed that rapid and slow pattern patients reached C-RP reduction >90% from baseline at Days 6 and 10, respectively. No response pattern had C-RP peaking at Day 3 and eventually gradually reducing within 2 weeks. CONCLUSION: Despite optimal meropenem PK/PD target attainment, C-RP decreases in no more than one-fourth of onco-haematological patients during the first 2 weeks of treatment. Among no-response patients, C-RP should be associated with other biomarkers to discriminate subjects with favourable clinical outcome.
Authors 8
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Affiliation as printed
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
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Pier Giorgio Cojutti corresponding
Affiliation as printed
Clinical Pharmacology Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
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Affiliation as printed
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research Leiden University Leiden The Netherlands
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Humanitas University · IRCCS Humanitas Research Hospital
Affiliation as printed
Department of Biomedical Sciences Humanitas University Pieve Emanuele Italy
Infectious Diseases Unit IRCSS Humanitas Research Hospital Rozzano Italy
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Affiliation as printed
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
Infectious Diseases Unit, Department for Integrated Infectious Risk Management IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy
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Istituto di Ematologia di Bologna · University of Bologna
Affiliation as printed
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
Istituto di Ematologia “Seràgnoli” IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy
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Affiliation as printed
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
Infectious Diseases Unit, Department for Integrated Infectious Risk Management IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy
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Affiliation as printed
Clinical Pharmacology Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy
Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna Bologna Italy
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