Open AccessImaging Enterobacterales infections in patients using pathogen-specific positron emission tomography
Author(s) -
Alvaro A. Ordoñez,
Luz M. Wintaco,
Fernando Mota,
Andrés Fernando Mejía Restrepo,
Camilo A. Ruiz-Bedoya,
Carlos Reyes,
Luis Guillermo Vasco Uribe,
Sudhanshu Abhishek,
Franco R. D’Alessio,
Daniel P. Holt,
Robert F. Dannals,
Steven P. Rowe,
Víctor R Castillo,
Martin G. Pomper,
Ulises Granados,
Sanjay Jain
Publication year - 2021
Publication title -
science translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.819
H-Index - 216
eISSN - 1946-6242
pISSN - 1946-6234
DOI - 10.1126/scitranslmed.abe9805
Subject(s) - positron emission tomography , medicine , pathogen , pneumonia , microbiology and biotechnology , klebsiella pneumoniae , biology , nuclear medicine , immunology , escherichia coli , biochemistry , gene
Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[ 18 F]fluoro-d-sorbitol ( 18 F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18 F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18 F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18 F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18 F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18 F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18 F-FDS from commercially available 2-deoxy-2-[ 18 F]fluoro-d-glucose ( 18 F-FDG) at room temperature. In a hamster model, 18 F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia-a leading cause of complications in hospitalized patients with COVID-19. These data support 18 F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.