Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Here, guided by recent advances in clinically relevant optical imaging technologies, we explore the use of fluorescently labelled vancomycin (vanco-800CW) to specifically target and detect infections caused by Gram-positive bacteria. The application potential of vanco-800CW for real-time in vivo imaging of bacterial infections is assessed in a mouse myositis model and a human post-mortem implant model. We show that vanco-800CW can specifically detect Gram-positive bacterial infections in our mouse myositis model, discriminate bacterial infections from sterile inflammation in vivo and detect biomaterial-associated infections in the lower leg of a human cadaver. We conclude that vanco-800CW has a high potential for enhanced non-invasive diagnosis of infections with Gram-positive bacteria and is a promising candidate for early-phase clinical trials.

FP-7 Framework Programme BetaCure and SurgVision BV.

Bacterial infections represent an increasing problem in modern health care, in particular due to ageing populations and accumulating bacterial resistance to antibiotics. Diagnosis is rarely straightforward and consequently treatment is often delayed or indefinite. Therefore, novel tools that can be clinically implemented are urgently needed to accurately and swiftly diagnose infections. Especially, the direct imaging of infections is an attractive option. The challenge of specifically imaging bacterial infections in vivo can be met by targeting bacteria with an imaging agent. Here we review the current status of targeted imaging of bacterial infections, and we discuss advantages and disadvantages of the different approaches. Indeed, significant progress has been made in this field and the clinical implementation of targeted imaging of bacterial infections seems highly feasible. This was recently highlighted by the use of so-called smart activatable probes and a fluorescently labelled derivative of the antibiotic vancomycin. A major challenge remains the selection of the best imaging probes, and we therefore present a set of target selection criteria for clinical implementation of targeted bacterial imaging. Altogether, we conclude that the spectrum of potential applications for targeted bacterial imaging is enormous, ranging from fundamental research on infectious diseases to diagnostic and therapeutic applications.