Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.

Autor: Troisi C; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy., Cojutti PG; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. piergiorgio.cojutti@unibo.it.; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. piergiorgio.cojutti@unibo.it., Rinaldi M; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.; Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Tonetti T; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.; Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Siniscalchi A; Anesthesiology and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., van Hasselt C; Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Viale P; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.; Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Pea F; Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Jazyk: angličtina
Zdroj: Clinical pharmacokinetics [Clin Pharmacokinet] 2024 Nov; Vol. 63 (11), pp. 1573-1583. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1007/s40262-024-01436-6
Abstrakt: Background and Objective: Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP).
Methods: Patients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti-Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [C ss ] to minimum inhibitory concentration [MIC] ratio = 4-8), quasi-optimal (C ss /MIC = 1-4) and sub-optimal (C ss /MIC < 1) and the magnitude of C-RP production inhibition over time.
Results: A total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10).
Conclusion: Our PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy.
Competing Interests: Declarations Ethics Approval and Consent to Participate The study was approved by the Local Ethics Committee (No. 308/2021/Oss/AOUBo on 24 May 2021). Consent for Publication Due to the retrospective nature of this investigation, informed written consent was waived. Availability of Data and Materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding This project has received funding from European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 861323. Authors' Contributions CT analyzed and wrote the initial manuscript; PGC wrote the manuscript and interpreted patient data; MR collected patient data; TT collected and analyzed patient data; AS collected and analyzed patient data; CvH, PV and FP supervised the project.
(© 2024. The Author(s).)
Databáze: MEDLINE
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