Epidemiological and clinical changes, role of [18F] FDG-PET/CT in the diagnosis and management and new antibiotic treatments of cardiac implantable electronic device infections

Abstract

[eng] 1. INTRODUCTION: In recent decades, there have been advances in cardiac electrostimulation (ECD) devices, with an increase in the number of implants and more sophisticated DEC, on an older target population with more comorbidities, which leads to higher infection rates and higher morbidity and mortality. In this doctoral thesis, the aim is to analyze the new epidemiological, clinical, diagnostic imaging (positron emission tomography with 18F Fluorodeoxyglucose [18F FDG-PET/CT] and transesophageal echocardiography [TEE]), management of infected DECs that cannot be removed and new antimicrobial treatment strategies in the experimental endocarditis model. It has been studied in the last four decades in a single institution (Hospital Clínic de Barcelona [HCB]) and has also been analysed in the European framework, through the International Collaboration on Endocarditis (ICE)), paying special attention to its most severe form, infective endocarditis (IE) on DEC.

2. HYPOTHESIS: HYPOTHESIS 1: The prevalence has increased and the profile has changed in IE in general and IE on DEC, with an increase in complexity and decreased survival. HYPOTHESIS 2: [18]FDG-PET/CT has a high sensitivity and specificity in pocket infections, which will decrease in the remaining segments of the DEC. Combined with TEE, systemic infections could be better diagnosed, and negative [18]FDG-PET/CT could guide the duration of suppressive antibiotic therapy (SAT) in cases of non-withdrawal of DEC.

HYPOTHESIS 3:

The proportion of patients with CAD infections without complete withdrawal of the CAD has increased due to host-dependent factors rather than device complexity. SAD may prevent recurrences. HYPOTHESIS 4: The combination of daptomycin plus ceftaroline will be synergistic and bactericidal in vitro and in vivo in methicillin-resistant Staphylococcus epidermdis (MRSE) and vancomycin (RSSE) infections.

3. OBJECTIVES:

OBJECTIVE 1: To learn about the changes in EI in Europe during the 21st century and to analyse possible interregional differences. To study the evolution of IE on DEC over 40 years and to identify prognostic factors for survival at one year. OBJECTIVE 2:

To study the diagnostic cost-effectiveness of [18F]FDG-PET/CT in the four topographic regions of the DEC. To determine its performance in systemic infections in combination with TEE and whether spleen/bone marrow hypermetabolism distinguishes between local and systemic infections. Determine its usefulness in safely discontinuing TAS. OBJECTIVE 3: To know the prevalence and identify the risk factors associated with the complete non-withdrawal of the DEC. To evaluate the safety and efficacy of the SAD. OBJECTIVE 4: To study the in-vitro and in-vivo activity of the combination of daptomycin and ceftaroline against MRSE and RSSE.

[spa] 1. INTRODUCTION: In recent decades, there have been advances in cardiac electrostimulation (ECD) devices, with an increase in the number of implants and more sophisticated DEC, on an older target population with more comorbidities, which leads to higher infection rates and higher morbidity and mortality. In this doctoral thesis, the aim is to analyze the new epidemiological, clinical, diagnostic imaging (positron emission tomography with 18F Fluorodeoxyglucose [18F FDG-PET/CT] and transesophageal echocardiography [TEE]), management of infected DECs that cannot be removed and new antimicrobial treatment strategies in the experimental endocarditis model. It has been studied in the last four decades in a single institution (Hospital Clínic de Barcelona [HCB]) and has also been analysed in the European framework, through the International Collaboration on Endocarditis (ICE)), paying special attention to its most severe form, infective endocarditis (IE) on DEC.

2. HYPOTHESIS: HYPOTHESIS 1: The prevalence has increased and the profile has changed in IE in general and IE on DEC, with an increase in complexity and decreased survival. HYPOTHESIS 2: [18]FDG-PET/CT has a high sensitivity and specificity in pocket infections, which will decrease in the remaining segments of the DEC. Combined with TEE, systemic infections could be better diagnosed, and negative [18]FDG-PET/CT could guide the duration of suppressive antibiotic therapy (SAT) in cases of non-withdrawal of DEC.

HYPOTHESIS 3:

The proportion of patients with CAD infections without complete withdrawal of the CAD has increased due to host-dependent factors rather than device complexity. SAD may prevent recurrences. HYPOTHESIS 4: The combination of daptomycin plus ceftaroline will be synergistic and bactericidal in vitro and in vivo in methicillin-resistant Staphylococcus epidermdis (MRSE) and vancomycin (RSSE) infections.

3. OBJECTIVES:

OBJECTIVE 1: To learn about the changes in EI in Europe during the 21st century and to analyse possible interregional differences. To study the evolution of IE on DEC over 40 years and to identify prognostic factors for survival at one year. OBJECTIVE 2:

To study the diagnostic cost-effectiveness of [18F]FDG-PET/CT in the four topographic regions of the DEC. To determine its performance in systemic infections in combination with TEE and whether spleen/bone marrow hypermetabolism distinguishes between local and systemic infections. Determine its usefulness in safely discontinuing TAS. OBJECTIVE 3: To know the prevalence and identify the risk factors associated with the complete non-withdrawal of the DEC. To evaluate the safety and efficacy of the SAD. OBJECTIVE 4: To study the in-vitro and in-vivo activity of the combination of daptomycin and ceftaroline against MRSE and RSSE.