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Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.
This article was published in the following journal.
Name: Journal of controlled release : official journal of the Controlled Release Society
Staphylococcus aureus (S. aureus) is one of the most common pathogens causing nosocomial and community-acquired infections which associate with high morbidity and mortality rates. Mupirocin has been i...
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A species of STAPHYLOCOCCUS similar to STAPHYLOCOCCUS HAEMOLYTICUS, but containing different esterases. The subspecies Staphylococcus hominis novobiosepticus is highly virulent and novobiocin resistant.
Lung infections with the invasive forms of ASPERGILLUS, usually after surgery, transplantation, prolonged NEUTROPENIA or treatment with high-doses of CORTICOSTEROIDS. Invasive pulmonary aspergillosis can progress to CHRONIC NECROTIZING PULMONARY ASPERGILLOSIS or hematogenous spread to other organs.
A COAGULASE-negative species of STAPHYLOCOCCUS found on the skin and MUCOUS MEMBRANE of warm-blooded animals. Similar to STAPHYLOCOCCUS EPIDERMIDIS and STAPHYLOCOCCUS HAEMOLYTICUS, it is a nosocomial pathogen in NICU settings. Subspecies include generally antibiotic susceptible and BIOFILM negative capitis and antibiotic resistant and biofilm positive urealyticus isolates.
A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing.
Viruses whose host is Staphylococcus.
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