Ahsan Akram and colleagues have created a fluorescent imaging probe that can quickly and accurately detect hard-to-trace Gram-negative bacteria (one of the major bacterial groups) in human lungs within minutes. Their first-in-human study, where they successfully used the imaging tool to safely detect infections in hospital patients undergoing ventilation, could streamline the diagnosis of bacterial lung infections and more accurately assess if antibiotics are needed. Patients in intensive care units (ICUs) who are placed on ventilators can be especially vulnerable to hospital-acquired gram-negative bacterial respiratory infections like pneumonia, underscoring an urgent need for faster diagnosis and better patient outcomes. However, existing approaches such as lung biopsies are risky procedures in ventilated patients, and sequencing techniques are overly sensitive. To overcome these limitations, Akram et al. developed an imaging probe that can rapidly visualize Gram-negative bacteria in human lungs in real-time. The probe consists of a fluorescent molecule attached to a molecule called polymyxin, which has antimicrobial properties and can bind to the outer membrane of Gram-negative bacteria. The scientists first tested it in the lungs of ventilated sheep infected with various Gram-negative bacteria, then they administered the molecule to six patients with bronchiectasis, a chronic pulmonary disease. Imaging videos demonstrate the method could track Gram-negative bacteria in the patients, a finding that was repeated when the probe was administered to seven ventilated ICU patients. Importantly, the platform was non-toxic and caused no major adverse effects, but the authors caution that future research should investigate the risks associated with the technology's repeated use.