Troisi, Carla
(2024)
Tailoring meropenem treatment for critically ill patients with hospital-acquired or ventilator associated pneumonia: a personalized PK/PD approach, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze e tecnologie della salute, 36 Ciclo. DOI 10.48676/unibo/amsdottorato/11363.
Documenti full-text disponibili:
![[img]](http://amsdottorato.unibo.it/style/images/fileicons/application_pdf.png) |
Documento PDF (English)
- Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (14MB)
|
Abstract
Critically ill patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) pose a formidable challenge in clinical management due to the profound alterations in their pharmacokinetics (PK).
Meropenem is a treatment option for HAP/VAP and its efficacy target is its concentration (Css) to minimum inhibitory concentration (MIC) ratio (Css/MIC) of 4-8.
This thesis aims to investigate strategies for optimizing meropenem PK and PD in critically ill patients with HAP/VAP.
To enhance meropenem PK optimization in critically ill patients, I evaluated the performance of various methods for estimating renal function, which is crucial for dosing adjustments. These methods included the measurement of creatinine clearance (mCLCR) and its estimation using empiric equations.
For PD optimization of meropenem in patients with HAP/VAP, I developed a PK/PD model to quantify the relationships between meropenem concentrations and changes in C-reactive protein (C-RP), an inflammation biomarker. Then, I simulated C-RP fate for different Css/MIC scenarios.
In the first project, results showed that dose adjustments of meropenem should be based on mCLCR. The use of equations for GFR estimation may result in significant under- or overestimation of meropenem dosages.
In the second project, I successfully built a PK/PD model. Simulations demonstrated that higher Css/MIC ratios were associated with greater and faster reductions in C-RP from baseline.
This research endeavors to personalize the treatment of critically ill patients with HAP/VAP treated with meropenem. It is essential to optimize both PK and PD aspects of therapy. The measurement of creatinine clearance (mCLCR) is essential, and empirical estimation formulas should not be relied upon. Regarding the PD, C-RP serves as a biomarker reflecting meropenem’s efficacy and can be used in clinical practice to assess whether the PK/PD efficacy target has been achieved.
Abstract
Critically ill patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) pose a formidable challenge in clinical management due to the profound alterations in their pharmacokinetics (PK).
Meropenem is a treatment option for HAP/VAP and its efficacy target is its concentration (Css) to minimum inhibitory concentration (MIC) ratio (Css/MIC) of 4-8.
This thesis aims to investigate strategies for optimizing meropenem PK and PD in critically ill patients with HAP/VAP.
To enhance meropenem PK optimization in critically ill patients, I evaluated the performance of various methods for estimating renal function, which is crucial for dosing adjustments. These methods included the measurement of creatinine clearance (mCLCR) and its estimation using empiric equations.
For PD optimization of meropenem in patients with HAP/VAP, I developed a PK/PD model to quantify the relationships between meropenem concentrations and changes in C-reactive protein (C-RP), an inflammation biomarker. Then, I simulated C-RP fate for different Css/MIC scenarios.
In the first project, results showed that dose adjustments of meropenem should be based on mCLCR. The use of equations for GFR estimation may result in significant under- or overestimation of meropenem dosages.
In the second project, I successfully built a PK/PD model. Simulations demonstrated that higher Css/MIC ratios were associated with greater and faster reductions in C-RP from baseline.
This research endeavors to personalize the treatment of critically ill patients with HAP/VAP treated with meropenem. It is essential to optimize both PK and PD aspects of therapy. The measurement of creatinine clearance (mCLCR) is essential, and empirical estimation formulas should not be relied upon. Regarding the PD, C-RP serves as a biomarker reflecting meropenem’s efficacy and can be used in clinical practice to assess whether the PK/PD efficacy target has been achieved.
Tipologia del documento
Tesi di dottorato
Autore
Troisi, Carla
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
PK/PD, HAP/VAP, beta-lactams, critically ill patients, personalized treatment, biomarkers, C-RP, clearance, meropenem
URN:NBN
DOI
10.48676/unibo/amsdottorato/11363
Data di discussione
27 Marzo 2024
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Troisi, Carla
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
PK/PD, HAP/VAP, beta-lactams, critically ill patients, personalized treatment, biomarkers, C-RP, clearance, meropenem
URN:NBN
DOI
10.48676/unibo/amsdottorato/11363
Data di discussione
27 Marzo 2024
URI
Statistica sui download
Gestione del documento: