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Antimicrobial Agents and Chemotherapy, January 2009, p. 249-255, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00691-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of a Novel Nanoemulsion against Burkholderia and Other Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species{triangledown}

John J. LiPuma,1,2* Sivaprakash Rathinavelu,2 Bridget K. Foster,1 Jordan C. Keoleian,1 Paul E. Makidon,2,3 Linda M. Kalikin,1 and James R. Baker Jr.2

Department of Pediatrics and Communicable Diseases,1 Michigan Nanotechnology Institute for Medicine and the Biological Sciences,2 Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan3

Received 27 May 2008/ Returned for modification 10 August 2008/ Accepted 2 October 2008

Respiratory tract infection, most often involving opportunistic bacterial species with broad-spectrum antibiotic resistance, is the primary cause of death in persons with cystic fibrosis (CF). Species within the Burkholderia cepacia complex are especially problematic in this patient population. We investigated a novel surfactant-stabilized oil-in-water nanoemulsion (NB-401) for activity against 150 bacterial isolates recovered primarily from CF respiratory tract specimens. These specimens included 75 Burkholderia isolates and 75 isolates belonging to other CF-relevant species including Pseudomonas, Achromobacter, Pandoraea, Ralstonia, Stenotrophomonas, and Acinetobacter. Nearly one-third of the isolates were multidrug resistant, and 20 (13%) were panresistant based on standard antibiotic testing. All isolates belonging to the same species were genotyped to ensure that each isolate was a distinct strain. The MIC90 of NB-401 was 125 µg/ml. We found no decrease in activity against multidrug-resistant or panresistant strains. MBC testing showed no evidence of tolerance to NB-401. We investigated the activity of NB-401 against a subset of strains grown as a biofilm and against planktonic strains in the presence of CF sputum. Although the activity of NB-401 was decreased under both conditions, the nanoemulsion remained bactericidal for all strains tested. These results support NB-401's potential role as a novel antimicrobial agent for the treatment of infection due to CF-related opportunistic pathogens.

* Corresponding author. Mailing address: Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W. Medical Center Dr., 8323 MSRB III, SPC 5646, Ann Arbor, MI 48109. Phone: (734) 615-5909. Fax: (734) 764-4279. E-mail: jlipuma{at}umich.edu

{triangledown} Published ahead of print on 27 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 249-255, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00691-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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