Liposomal co-delivery of daptomycin and clarithromycin at an optimized ratio for treatment of methicillin-resistant Staphylococcus aureus infection.
BACKGROUND
Pathogen evolution currently outpaces novel drug development, and because development of new antibiotics is pending, combination therapy with existing drugs may provide effective alternative treatments.


OBJECTIVE
The present study was aimed at evaluating the concurrent use of two antibiotics, daptomycin and clarithromycin, against methicillin-resistant Staphylococcus aureus (MRSA) infections.


METHODS
Polyeythylene glycol (PEGylated liposomes loaded with daptomycin, clarithromycin, or both (PL[CD]) at an optimized mass ratio of 1:32 were generated and characterized using dynamic light scattering and electron microscopy. In vitro and in vivo approaches were used to compare liposome effects on MRSA.


RESULTS
PL[CD] were stable, with a mean (± SD) vesicle diameter of 98.2 ± 2.21 nm and encapsulation efficiency of 94.71 ± 1.37% (daptomycin) and 92.94 ± 1.21% (clarithromycin). Compared with daptomycin-only liposomes, PL[CD] showed significantly enhanced anti-MRSA activity in vitro and significantly reduced MRSA bacterial load and increased host survival in vivo.


CONCLUSIONS
Co-delivery of daptomycin with clarithromycin produced significant anti-MRSA activity in the presence of only one-thirtieth of the concentration required in liposomes containing daptomycin only.


CONCLUSIONS
These findings suggested that concurrent liposomal delivery of daptomycin and clarithromycin has the potential to be an effective and less toxic treatment for MRSA infections.
Department of Pharmaceutics, College of Pharmaceutical Sciences, Southwest University , Chongqing , People's Republic of China.
Yanhong
Y
Li
Tingting
T
Su
Yan
Y
Zhang
Xingliang
X
Huang
Jing
J
Li
Chong
C
Li
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008081:Liposomes / Q000494:pharmacology* / Q000627:therapeutic use; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D017291:Clarithromycin; D017576:Daptomycin
Antibiotics; combination chemotherapy; liposome; severe infections