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Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis.
Antimicrob Agents Chemother. 2007 Jan; 51(1):23-7.AA

Abstract

Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM.

Authors+Show Affiliations

Department of Biomedical Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107-1898, USA. shannongoswick@sbcglobal.netNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17060522

Citation

Soltow, Shannon M., and George M. Brenner. "Synergistic Activities of Azithromycin and Amphotericin B Against Naegleria Fowleri in Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis." Antimicrobial Agents and Chemotherapy, vol. 51, no. 1, 2007, pp. 23-7.
Soltow SM, Brenner GM. Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. Antimicrob Agents Chemother. 2007;51(1):23-7.
Soltow, S. M., & Brenner, G. M. (2007). Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. Antimicrobial Agents and Chemotherapy, 51(1), 23-7.
Soltow SM, Brenner GM. Synergistic Activities of Azithromycin and Amphotericin B Against Naegleria Fowleri in Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis. Antimicrob Agents Chemother. 2007;51(1):23-7. PubMed PMID: 17060522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. AU - Soltow,Shannon M, AU - Brenner,George M, Y1 - 2006/10/23/ PY - 2006/10/25/pubmed PY - 2007/7/3/medline PY - 2006/10/25/entrez SP - 23 EP - 7 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 51 IS - 1 N2 - Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/17060522/Synergistic_activities_of_azithromycin_and_amphotericin_B_against_Naegleria_fowleri_in_vitro_and_in_a_mouse_model_of_primary_amebic_meningoencephalitis_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=17060522 DB - PRIME DP - Unbound Medicine ER -