Imaging agents highlight bacterial infections, may curb ICD complications

Maltodextrin imaging agents can distinguish bacterial infections from inflamed areas, according to a rat study published in JACC: Cardiovascular Imaging. Ideally, this finding could lead to novel tracers to catch infections from implanted cardiac devices (ICDs) before they require removal.

Senior study author W. Robert Taylor, MD, PhD, of Emory University School of Medicine, and colleagues inserted stainless steel mock ICDs into rats for the study. Four days later, they treated them three different ways: by inducing a mild infection, inducing noninfectious inflammation or doing nothing at all (control group).

Two days after that, tracers were injected and the rats were run through imaging tests.

A maltohexaose fluorescent dye probe (MDP) showed an intensity ratio of 1.54 in infected rats versus 1.26 and 1.20 in the control and inflammatory groups, respectively. This difference persisted for 24 hours and was enough to clearly distinguish the infected rats from the others, the authors noted.

“No significant difference was found between the noninfectious inflammation group and the control group, demonstrating the specificity of the MDP to detect infection as opposed to inflammation,” they wrote. “These data indicated that the MDP accumulated in the site of infection in a highly specific manner with an excellent signal-to-noise ratio.”

Positron emission tomography (PET) imaging showed that another maltodextrin-based agent, F18 fluoromaltohexaose, accumulated significantly at the location of infection. There was no significant accumulation in control rats or those who had noninfectious inflammation. Another radiotracer, F18 fluorodeoxyglucose, was found to cluster in both inflamed and infected areas and therefore would be less useful for clinical decision-making.

Taylor et al. said it is difficult to identify infections in the skin pockets around ICDs. Routine inflammation can have a similar early appearance, complicating diagnoses. Often an infection is identified too late for removal, which can be dangerous and costly.   

“The number of hospital admissions for CIED (cardiovascular implantable electronic device) infections has increased three-fold over an 8-year period, paralleling a similar increase in the number of device infections,” the researchers wrote. “Importantly, pocket infections are associated with at least a doubling of mortality. The incremental cost associated with infection of an implantable electronic cardiac device is estimated to be in excess of $50,000 per patient.”

Taylor and colleagues said they intentionally induced a mild infection in the rats to mimic a subclinical condition. Considering FDG and F18 fluoromaltohexaose were still able to highlight infections at this early stage, the authors said it might be possible to use these methods to prescribe antibiotics before device extraction is necessary.

“This strategy has the potential to positively impact the morbidity and mortality as well as the healthcare costs associated with infections of implanted medical devices,” Taylor and coauthors wrote.

In a related editorial, three researchers from the University of Maryland School of Medicine said maltodextrins are especially attractive because they are used as food additives and have low toxicity to humans. However, they noted it is unclear what Taylor et al. considered a “mild infection” in mice and what that would translate to in humans. The specificity of the imaging tests relies on the amount of tracer accumulated in a target region—which would be influenced by the severity of the infection—as well as the spatial resolution of PET.

“If the total number of bacteria is low, or the bacteria are engulfed by leukocytes and unable to access the tracer, then it is possible that the tracer signal might not be high enough to be detected by PET,” wrote Mohammad M. Sajadi, MD, and his editorial coauthors. “This is particularly critical, because most of the current nondigital PET machines have a poor spatial resolution of about six millimeter, with associated partial volume effect for small lesions. Although the poor spatial resolution of PET can be compensated by a high local tracer signal, this might not be the case for mild infection with a small number of bacteria.”