Imagenología de las infecciones por Enterobacterales a través del estudio por Tomografía por Emisión de Positrones con 18F-Fluorodeoxisorbitol

Abstract

Enterobacterales are a large group of Gram-negative bacteria some species are part of the intestinal microbiome of humans and some animals. Currently, it represents a public health problem and a challenge in daily clinical practice due to the increased resistance to antibiotics available for treatment and the high rates of morbidity and mortality reported throughout the world. These infections are related to Health Care-Associated Infections (HAI) and represent many of them. To date, the diagnosis of these bacterial infections continues to be microbiological identification, which can take between 3 or 4 days, from obtaining the biological sample from the site where the infection is suspected to its identification. However, this methodology has some limitations, such as the need to obtain a clinical sample to isolate and identify the causal agent of the infection, which is not always possible or easy to get; either because the exact location of the infection site is unknown or because invasive procedures are required that represent more risks than benefits for the patient. Taking the above into account, it is urgent to develop new rapid and specific diagnostic methods that allow the identification of infections caused by Enterobacterales in less time and with greater sensitivity. Therefore, a group of researchers identified the radiotracer 18F-Fluorodeoxysorbitol known as (18F-FDS); a specific metabolic substrate for Enterobacterales, which through the srl operon made up of 3 subunits that constitute the sorbitol-dependent phosphotransferase system, which allows sorbitol to enter the interior of the bacterium to be metabolized via glycolysis (1). Subsequently, experiments (in vitro) with different families of bacteria and eukaryotic cell lines made it possible to determine their absorption and establish the specificity for this type of bacteria, just as experiments (in vivo) in a murine infection model made it possible to correctly determine the foci of infection caused by Enterobacterales from sites with sterile inflammation and infections caused by other types of bacteria (2). Subsequently, they carried out Positron Emission Tomography (PET) and Computed Tomography (CT) studies with 18F-FDS in healthy people without foci of infection to analyze their biodistribution and dosimetry, obtaining excellent results that allowed determining the radioactive activity that should be injected from 18F-FDS and ensure safe use in humans (3). Based on the above results, a PET radiotracer is recommended as a possible candidate to identify specific foci of infection caused by Enterobacterales. The reason why; The main objective of this research was to evaluate the diagnostic utility of the 18F-FDS radiotracer using the PET/CT technique in 13 hospitalized patients of legal age with high clinical suspicion of infections caused by Enterobacterales, treated at the Fundación Cardiovascular de Colombia ( FCV). Between 2018-2020, in addition to evaluating the response to antibiotic therapy once treatment was completed, through a second PET/CT control study with 18F-FDS. This study began with the standardization of the synthesis of the 18F-FDS radiotracer from the chemical reduction of 18-Fluorodeoxyglucose (18F-FDG), a radiotracer widely used in the daily clinical practice of Nuclear Medicine once this stage is completed, the search begins for participants with a high suspicion of infection caused by Enterobacterales. They meet the inclusion criteria previously defined by the group of researchers and approved by the Ethics Committee of the Fundación Cardiovascular de Colombia (FCV) to carry out the PET/CT studies with 18F-FDS and finally, to analyze each of the molecular images obtained from the participants that would allow locating the exact place of the infection together with the microbiological confirmation. In addition, perform a second PET/CT control study with 18F-FDS post-antibiotic therapy to evaluate its evolution. The correct standardization of the synthesis of 18F-FDS and the precise analysis of the molecular images obtained using PET/CT allowed us to quickly and precisely identify the foci of infection formed by the Enterobacterales in the 13 participants together with the microbiological confirmation and further evaluate the response to antibiotic treatment through a second PET/CT control study with 18F-FDS that made it possible to see the effect of antibiotic therapy and the evolution of the initially identified sources of infection. In addition, analyze in which cases the performance of the PET/CT study with 18F-FDS can be of greater clinical utility so that in the future it can be implemented during the practice of Nuclear Medicine (4). The results of this thesis allowed (I) to carry out the correct synthesis of 18F-FDS from 18F-FDG in a fast, safe manner with high radiochemical and microbiological quality (II) To evaluate the clinical utility of the 18F-FDS radiotracer, which is showed bacterial selectivity to quickly identify foci of infection caused by Enterobacterales in different tissues and microenvironments of the body, without its absorption being affected by the location of the infection, (III) Analyze by molecular imaging (in vivo ) the evolution of foci of infection caused by Enterobacterales after antibiotic therapy. In addition, evaluate its possible clinical applications for both diagnosis and monitoring of infections, (4) Describe the clinical importance of Health Care-Associated Infections and their relationship with Enterobacterales. Finally, it is important to highlight that this study is the first of its kind carried out in the world; where the clinical utility of the PET/CT study with 18F-FDS in humans damaged by Enterobacterales is being evaluated, which will be a reference in the future for the development of new clinical studies with 18F-FDS and its implementation in Nuclear Medicine.