Antibiotic resistance is a global health threat. There are a few
antibiotics under development, and even fewer with new modes of action and no cross-resistance to established
antibiotics. Accordingly, reformulation of old
antibiotics to overcome resistance is attractive. Nano-
mupirocin is a PEGylated nano-liposomal formulation of
mupirocin, potentially enabling parenteral use in deep
infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of
mupirocin and Nano-
mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-
mupirocin in a rat model. Nano-
mupirocin showed no cross-resistance with other
antibiotics and retained full activity against
vancomycin-,
daptomycin-,
linezolid- and methicillin- resistant Staphylococcus aureus, against
vancomycin-resistant Enterococcus faecium, and
cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-
mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that
mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-
mupirocin has excellent potential for treatment of several
infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established
antibiotic and
liposomes of the same size and
lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.