CONTEXT: 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. MATERIALS AND 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. DISCUSSION: 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. CONCLUSION: 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.
CONTEXT: 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. MATERIALS AND 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. DISCUSSION: 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. CONCLUSION: 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.
Entities:
Keywords:
Antibiotics; combination chemotherapy; liposome; severe infections
Authors: Marcin Makowski; Ítala C Silva; Constança Pais do Amaral; Sónia Gonçalves; Nuno C Santos Journal: Pharmaceutics Date: 2019-11-08 Impact factor: 6.321