Tesi etd-11022021-225607
Link copiato negli appunti
Tipo di tesi
Corso Ordinario Ciclo Unico 6 Anni
Autore
BALICE, GIUSEPPE
URN
etd-11022021-225607
Titolo
Daptomycin usage in infective endocarditis: literature review and pharmacometric approach
Struttura
Cl. Sc. Sperimentali - Medicina
Corso di studi
SCIENZE MEDICHE - SCIENZE MEDICHE
Commissione
relatore Prof. PASSINO, CLAUDIO
Relatore Prof. DI PAOLO, ANTONELLO
Membro Prof. EMDIN, MICHELE
Membro Prof. LIONETTI, VINCENZO
Membro Prof. COCEANI, FLAVIO
Membro Prof. RECCHIA, FABIO ANASTASIO
Membro Prof. GIANNONI, ALBERTO
Membro Prof. ANGELONI, DEBORA
Membro Dott.ssa CASIERI, VALENTINA
Relatore Prof. DI PAOLO, ANTONELLO
Membro Prof. EMDIN, MICHELE
Membro Prof. LIONETTI, VINCENZO
Membro Prof. COCEANI, FLAVIO
Membro Prof. RECCHIA, FABIO ANASTASIO
Membro Prof. GIANNONI, ALBERTO
Membro Prof. ANGELONI, DEBORA
Membro Dott.ssa CASIERI, VALENTINA
Parole chiave
- daptomycin
- IE
- infective endocarditis
- MIPD
- model informed precision dosing
- POP/PK
- population pharmacokinetics
Data inizio appello
20/12/2021;
Disponibilità
parziale
Riassunto analitico
Daptomycin is a cyclic lipopeptide antibiotic that can be used in difficult-to-treat Gram positive infections, licensed up to 8mg/kg by FDA and EMA for use in right infectious endocarditis (RIE). The aim of the present work is to explore the effectiveness of daptomycin in other endocardial infections, such as left infectious endocarditis (LIE) and implantable cardiac device infections (ICDI).
A literature review combining the keywords “daptomycin” and “left infectious endocarditis” has been conducted. A total of 89 abstracts and articles after duplicates removal have been found. Further abstract-based refinement ended with selection of 7 cohort studies, 9 registry studies and 1 non-randomized case-control study. No randomized controlled trials have been yet conducted to investigate this subject, because of the discouraging initial results published at the time of daptomycin licensing for RIE. Nevertheless, in the present work the evidence resulting from literature review has been quantitatively synthetized, showing no difference between odds of clinical cure of RIE and LIE using daptomycin-based therapeutic schemes (95% CI of the OR: 0.41 – 1.42).
Moreover, a pharmacodynamic study has been conducted in the present work, using data collected from 67 patients enrolled at AOUP and FTGM hospitals. Clinical outcomes and covariates have been related to patients’ daptomycin AUC, which has been calculated using a previously developed pharmacometric model. The Cox proportional hazard model for the main outcome measure, that was the hospitalization time in days, showed a significative influence of the admission diagnosis (ICDI vs LIE, p = 0.023) and of the mean daptomycin AUC (p = 0.023).
In conclusion, the present work supports the critical role of model-informed precision dosing in ameliorating clinical outcomes and points out the need of further high-quality studies on the role of daptomycin in LIE treatment.
A literature review combining the keywords “daptomycin” and “left infectious endocarditis” has been conducted. A total of 89 abstracts and articles after duplicates removal have been found. Further abstract-based refinement ended with selection of 7 cohort studies, 9 registry studies and 1 non-randomized case-control study. No randomized controlled trials have been yet conducted to investigate this subject, because of the discouraging initial results published at the time of daptomycin licensing for RIE. Nevertheless, in the present work the evidence resulting from literature review has been quantitatively synthetized, showing no difference between odds of clinical cure of RIE and LIE using daptomycin-based therapeutic schemes (95% CI of the OR: 0.41 – 1.42).
Moreover, a pharmacodynamic study has been conducted in the present work, using data collected from 67 patients enrolled at AOUP and FTGM hospitals. Clinical outcomes and covariates have been related to patients’ daptomycin AUC, which has been calculated using a previously developed pharmacometric model. The Cox proportional hazard model for the main outcome measure, that was the hospitalization time in days, showed a significative influence of the admission diagnosis (ICDI vs LIE, p = 0.023) and of the mean daptomycin AUC (p = 0.023).
In conclusion, the present work supports the critical role of model-informed precision dosing in ameliorating clinical outcomes and points out the need of further high-quality studies on the role of daptomycin in LIE treatment.
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