OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) poses a major problem to public health worldwide. MRSA strains with increased resistance to vancomycin cause infections that are associated with greater morbidity and threaten the use of this once gold-standard antistaphylococcal drug. We investigated whether encapsulation of vancomycin within liposomes could improve its antistaphylococcal activity. METHODS: Two liposomal formulations of vancomycin were prepared using a rehydration-dehydration method. MICs and MBCs of the liposomal vancomycin for strains of MRSA were determined. The efficacy of one of the liposomal vancomycin formulations was also investigated in a time-kill assay in vitro and in a murine systemic infection model. RESULTS: Encapsulation in either liposome preparation decreased the vancomycin MICs and MBCs for MRSA strains by approximately 2-fold. Liposomal vancomycin increased killing of MRSA in vitro in a kinetic study. In a systemic murine infection model, treatment with a 50 mg/kg intraperitoneal injection of liposomal vancomycin improved kidney clearance of a USA300 strain by 1 log compared with an injection of 50 mg/kg of free vancomycin. CONCLUSIONS: Our findings suggest that entrapment within liposomes could improve the antistaphylococcal efficacy of vancomycin.
OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) poses a major problem to public health worldwide. MRSA strains with increased resistance to vancomycin cause infections that are associated with greater morbidity and threaten the use of this once gold-standard antistaphylococcal drug. We investigated whether encapsulation of vancomycin within liposomes could improve its antistaphylococcal activity. METHODS: Two liposomal formulations of vancomycin were prepared using a rehydration-dehydration method. MICs and MBCs of the liposomal vancomycin for strains of MRSA were determined. The efficacy of one of the liposomal vancomycin formulations was also investigated in a time-kill assay in vitro and in a murine systemic infection model. RESULTS: Encapsulation in either liposome preparation decreased the vancomycin MICs and MBCs for MRSA strains by approximately 2-fold. Liposomal vancomycin increased killing of MRSA in vitro in a kinetic study. In a systemic murine infection model, treatment with a 50 mg/kg intraperitoneal injection of liposomal vancomycin improved kidney clearance of a USA300 strain by 1 log compared with an injection of 50 mg/kg of free vancomycin. CONCLUSIONS: Our findings suggest that entrapment within liposomes could improve the antistaphylococcal efficacy of vancomycin.
Authors: Selina K Jorch; Bas Gj Surewaard; Mokarram Hossain; Moritz Peiseler; Carsten Deppermann; Jennifer Deng; Ania Bogoslowski; Fardau van der Wal; Abdelwahab Omri; Michael J Hickey; Paul Kubes Journal: J Clin Invest Date: 2019-11-01 Impact factor: 14.808
Authors: Gwendolyn M Pais; Jiajun Liu; Sanja Zepcan; Sean N Avedissian; Nathaniel J Rhodes; Kevin J Downes; Ganesh S Moorthy; Marc H Scheetz Journal: Pharmacotherapy Date: 2020-05-04 Impact factor: 4.705
Authors: Bas G J Surewaard; Justin F Deniset; Franz J Zemp; Matthias Amrein; Michael Otto; John Conly; Abdelwahab Omri; Robin M Yates; Paul Kubes Journal: J Exp Med Date: 2016-06-20 Impact factor: 14.307
Authors: Kushal Vanamala; Katyayani Tatiparti; Ketki Bhise; Samaresh Sau; Marc H Scheetz; Michael J Rybak; David Andes; Arun K Iyer Journal: Drug Discov Today Date: 2020-10-20 Impact factor: 7.851