[ZrO]2+[CLP]2- (CLP: clindamycinphosphate) inorganic-organic hybrid nanoparticles (IOH-NPs) represent a novel strategy to treat persisting, recurrent infections with multiresistant Staphylococcus aureus. [ZrO]2+[CLP]2- is prepared in water and contains the approved antibiotic with unprecedented high load (82 wt % CLP per nanoparticle). The IOH-NPs result in 70-150-times higher antibiotic concentrations at difficult-to-reach infection sites, offering new options for improved drug delivery for chronic and difficult-to-treat infections.