Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

• Published in: International journal of antimicrobial agents Vol. 32; no. 5; pp. 411 - 417
• Main Authors: Kim, Jong-Hyun, Lee, Yang-Jin, Sohn, Hae-Jin, Song, Kyoung-Ju, Kwon, Daeho, Kwon, Myung-Hee, Im, Kyung-Il, Shin, Ho-Joon
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2008; Elsevier
• Subjects: Amebiasis - drug therapy; Amebiasis - microbiology; Amebicides - pharmacology; Amebicides - therapeutic use; Amoeba; Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Blood Urea Nitrogen; Central Nervous System Protozoal Infections - drug therapy; Central Nervous System Protozoal Infections - microbiology; Female; Infectious Disease; Kidney - microbiology; Kidney - pathology; L-Lactate Dehydrogenase - metabolism; Liver - microbiology; Liver - pathology; Medical sciences; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Miocamycin - analogs & derivatives; Miocamycin - pharmacology; Miocamycin - therapeutic use; Naegleria fowleri; Naegleria fowleri - drug effects; PAME; Pharmacology. Drug treatments; Rokitamycin; Survival Analysis; Rokitamycin; PAME; Naegleria fowleri; Protozoa; Nervous system diseases; Macrolide; In vitro; Meningoencephalitis; Antibiotic; Treatment; FAME; Central nervous system disease; Parasiticide; Protein synthesis inhibitor; Antibacterial agent; Heterolobosea
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2008.05.018

Abstract Inhalation of freshwater containing the free-living amoeba Naegleria fowleri leads to a potentially fatal infection known as primary amoebic meningoencephalitis (PAME). Amphotericin B is the only agent with clinical efficacy in the treatment of PAME in humans, however this drug is often associated with adverse effects on the kidney and other organs. In an attempt to select other useful therapeutic agents for treating PAME, the amoebicidal activities of antibacterial agents including clarithromycin, erythromycin, hygromycin B, neomycin, rokitamycin, roxithromycin and zeocin were examined. Results showed that the growth of amoeba was effectively inhibited by treatment with hygromycin B, rokitamycin and roxithromycin. Notably, when N. fowleri trophozoites were treated with rokitamycin, the minimal inhibitory concentration was 6.25 μg/mL on Day 2. In the treatment of experimental meningoencephalitis due to N. fowleri , survival rates of mice treated with roxithromycin and rokitamycin were 25% and 80%, respectively, over 1 month. The mean time to death for roxithromycin and rokitamycin treatment was 16.2 days and 16.8 days, respectively, compared with 11.2 days for control mice. Finally, rokitamycin showed both in vitro and in vivo therapeutic efficacy against N. fowleri and may be a candidate drug for the treatment of PAME.