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.
Subject(s)
Anti-Bacterial Agents , Benzenesulfonates , Diagnostic Imaging/methods , Fluorescent Dyes , Gram-Positive Bacterial Infections/diagnosis , Indoles , Myositis/diagnosis , Vancomycin , Animals , Anti-Bacterial Agents/chemistry , Benzenesulfonates/chemistry , Biocompatible Materials/adverse effects , Cadaver , Disease Models, Animal , Fluorescent Dyes/chemistry , Gram-Positive Bacteria/growth & development , Gram-Positive Bacterial Infections/microbiology , Humans , Image Interpretation, Computer-Assisted , Indoles/chemistry , Mice , Myositis/microbiology , Time Factors , Vancomycin/chemistryABSTRACT
BACKGROUND: Patients in the ICU are thought to have abnormal circadian rhythms, but quantitative data are lacking. METHODS: To investigate circadian rhythms in the ICU, we studied core body temperatures over a 48-h period in 21 patients (59 ± 11 years of age; eight men and 13 women). RESULTS: The circadian phase position for 17 of the 21 patients fell outside the published range associated with morningness/eveningness, which determines the normative range for variability among healthy normal subjects. In 10 patients, the circadian phase position fell earlier than the normative range; in seven patients, the circadian phase position fell later than the normative range. The mean ± SD of circadian displacement in either direction (advance or delay) was 4.44 ± 3.54 h. There was no significant day-to-day variation of the 24-h temperature profile within each patient. Stepwise linear regression was performed to determine if age, sex, APACHE (Acute Physiology and Chronic Health Evaluation) III score, or day in the ICU could predict the patient-specific magnitude of circadian displacement. The APACHE III score was found to be significantly predictive of circadian displacement. CONCLUSIONS: The findings indicate that circadian rhythms are present but altered in patients in the ICU, with the degree of circadian abnormality correlating with severity of illness.
