Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide in treatment of experimental Klebsiella pneumoniae infection.
The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) on resistance to Klebsiella pneumoniae infection in mice was investigated. It was shown that administration of MTPPE, at 24 h before bacterial inoculation, led to a dose-dependent antibacterial resistance in terms of increased clearance of bacteria from the blood and bacterial killing in various organs. The lowest effective dose of MTPPE was 50 micrograms per mouse. Administration of liposome-encapsulated MTPPE was also effective at a dose of 25 micrograms per mouse. The time of administration of both free and liposome-encapsulated MTPPE, with respect to the appearance of bacteria in the blood, was very important and indicated that repeated administration is necessary to obtain protection for a prolonged period. In view of the toxicity of MTPPE, it was an important observation that repeated administration of MTPPE in the liposome-encapsulated form also produced antibacterial resistance. Administration of free and liposome-encapsulated MTPPE resulted in increased numbers of granulocytes, monocytes, and lymphocytes in the blood of uninfected mice and prevented leukopenia in infected mice.
Melissen
P M
PM
Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
van Vianen
W
W
Rijsbergen
Y
Y
Bakker-Woudenberg
I A
IA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D001769:Blood / Q000382:microbiology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005856:Germ-Free Life; D007275:Injections, Intravenous; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects; D008081:Liposomes; D008099:Liver / Q000382:microbiology; D051379:Mice; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors
D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine