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Antimicrobial Agents and Chemotherapy, January 2007, p. 23-27, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00788-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Synergistic Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis{triangledown}

Shannon M. Soltow* and George M. Brenner

Department of Biomedical Sciences, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma

Received 29 June 2006/ Returned for modification 7 August 2006/ Accepted 16 October 2006

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.


* Corresponding author. Mailing address: Department of Biomedical Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107-1898. Phone: (918) 561-8260. Fax: (918) 561-8414. E-mail: shannongoswick{at}sbcglobal.net.

{triangledown} Published ahead of print on 23 October 2006.


Antimicrobial Agents and Chemotherapy, January 2007, p. 23-27, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00788-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.