Abstract
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.
Highlights
Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat
We show that NIR optical imaging with a bacteria-specific vancomycin-based probe can detect both invasive infections in vivo and biomaterial-associated infections (BAIs) post mortem
To determine the binding specificity of vanco-800CW, bacterial isolates from infected orthopaedic material of 19 patients at the University Medical Center Groningen were cultured, incubated with vanco800CW and subsequently imaged with an IVIS Spectrum. These isolates form a representative display of the microorganisms encountered in BAIs, including S. aureus, Staphylococcus epidermidis, Corynebacterium species, Streptococcus or closely related bacterial species (Group G Streptococcus species, Streptococcus mitis and Granulicatella adiacens), Dermabacter hominis, Escherichia coli, Klebsiella species, Enterobacter species and Pseudomonas species
Summary
Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Guided by recent advances in clinically relevant optical imaging technologies, we explore the use of fluorescently labelled vancomycin (vanco-800CW) to target and detect infections caused by Gram-positive bacteria. Recent pioneering studies have demonstrated the feasibility of TFLI for in vivo detection of bacteria[9,10,11] Before introducing this approach into the clinic, several essential steps need to be carried out, including toxicity testing of the fluorescent probe for its clinical translation, according to international guidelines and standards such as the Good Clinical Practice guidelines (http://www.ich.org/products/guidelines.html). For usage as an optical imaging agent to selectively target Gram-positive bacteria in vivo, we conjugated vancomycin to IRDye 800CW, a near-infrared (NIR) fluorophore in early clinical trial (NCT01508572; Fig. 1a). We show that NIR optical imaging with a bacteria-specific vancomycin-based probe can detect both invasive infections in vivo and BAIs post mortem
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