@misc{10481/87432, year = {2018}, url = {https://hdl.handle.net/10481/87432}, abstract = {Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is criti cal for positive resolution of the infections and could be used for patient stratification and for monitoring treat ment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time. We used optical endomicroscopy to visualize a water-soluble optical imaging probe based on the antimicrobial peptide polymyxin conjugated to an environmentally sensitive fluoro phore. The probe was chemically stable and nontoxic and, after in-human intrapulmonary microdosing, enabled the specific detection of Gram-negative bacteria in distal human airways and alveoli within minutes. The results suggest that pulmonary molecular imaging using a topically administered fluorescent probe targeting bacterial lipid A is safe and practical, enabling rapid in situ identification of Gram-negative bacteria in humans.}, organization = {This work was supported by Wellcome Trust, the Department of Health Healthcare Innovation Challenge Fund (HICF-0510-069), and the Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration “Proteus” (EP/K03197X/1). The GMP activities were supported by the National Institute for Health Research (NIHR) BRC GMP Unit at Guy’s and St. Thomas’ NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.}, publisher = {American Association for the Advancement of Science}, keywords = {Gram negative bacteria}, keywords = {Optical imaging}, keywords = {Fluorescence}, title = {In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A}, doi = {10.1126/scitranslmed.aal0033}, author = {Akram, Ahsan R and Chankeshwara, Sunay V and Scholefield, Emma and Aslam, Tashfeen and McDonald, Neil and Megía Fernández, Alicia and Marshall, Adam and Mills, Bethany and Avlonitis, Nicolaos and Craven, Thomas H and Smyth, Annya M and Collie, David S and Gray, Calum and Hirani, Nik and Hill, Adam T and Govan, John R and Walsh, Timothy and Haslett, Christopher and Bradley, Mark and Dhaliwal, Kevin}, }