An alveolar macrophage-targeted ciprofloxacin polymeric prodrug improves survival in a murine model of Klebsiella pneumoniae pneumonia.

Klebsiella pneumoniae is a leading cause of both hospital- and community-acquired pneumonia. Nanomaterials have the potential to deliver antibiotics directly to sites of infection with improved pharmacokinetics and to avoid development of antimicrobial resistance. We previously demonstrated the use of alveolar macrophage (AM)-targeted polymeric prodrugs to prevent pneumonia in murine models caused by the facultative intracellular pathogens Francisella novicida and Burkholderia pseudomallei. These fully synthetic mannose-tagged polymers engage with AM mannose receptors, permitting uptake and triggering intracellular ciprofloxacin release. Here we show that the AMs can also serve as a reservoir for releasing antibiotics to treat infections caused by a primarily extracellular bacterium. Aerosolized ciprofloxacin polymeric prodrugs significantly improved survival in a murine model of K. pneumoniae pneumonia, reduced lung bacterial burden, lessened extent of lung injury, and prevented excessive neutrophilic inflammation.