Enhanced killing of methicillin-resistant Staphylococcus aureus in human macrophages by liposome-entrapped vancomycin and teicoplanin.
The antibacterial effects of liposomal vancomycin and teicoplanin against intracellular methicillin-resistant Staphylococcus aureus (MRSA) were evaluated using a macrophage infection model. Human blood-derived monocytes were cultured for 7 days to obtain adherent macrophages. Uptake of each drug by macrophages was markedly enhanced by liposomal encapsulation. Following phagocytosis and removal of residual extracellular MRSA, the infected macrophages were exposed to clinically achievable concentrations of teicoplanin and vancomycin. The free (untrapped) and liposome-entrapped forms of each drug were used at the same concentration. The number of intracellular surviving bacteria was determined by colony counts after lysis of the macrophages at different time intervals following drug treatment. Intracellular antimicrobial effect of each drug was significantly (p < 0.001) increased by entrapment in liposomes. Also, the efficacies of the free and liposomal forms of both drugs were correspondingly comparable (p > 0.05). It is, therefore, concluded that liposomal encapsulation of vancomycin and teicoplanin results in an increased availability of the antibiotics for efficient elimination of intracellular MRSA infection.
Dept. of Pharmacy and Research, Hartford Hospital, Connecticut 06115.
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Onyeji
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Nightingale
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Marangos
D001682:Biological Availability; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000382:microbiology*; D016106:Methicillin Resistance; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D017334:Teicoplanin / Q000493:pharmacokinetics / Q000494:pharmacology*; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology*
D004337:Drug Carriers; D008081:Liposomes; D017334:Teicoplanin; D014640:Vancomycin