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Antimicrobial Agents and Chemotherapy, September 2005, p. 3868-3874, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3868-3874.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of Intratracheal Administration of Novispirin G10 on a Rat Model of Mucoid Pseudomonas aeruginosa Lung Infection

Zhijun Song,^1* Hong Wu,¹ Per Mygind,² Dora Raventos,² Carsten Sonksen,² Hans-Henrik Kristensen,² and Niels Høiby¹

Department of Clinical Microbiology, University Hospital of Copenhagen, Copenhagen,¹ Anti-Infective Discovery, Novozymes A/S, Bagsvaerd, Denmark²

Received 15 November 2004/ Returned for modification 24 January 2005/ Accepted 9 June 2005

Chronic Pseudomonas aeruginosa lung infection is a major problem for patients with cystic fibrosis (CF). The biofilm mode of growth of the pathogen makes it highly resistant to antibiotic treatment, and this is especially pronounced with mucoid strains. In this study, novispirin G10, a synthetic antimicrobial peptide patterned loosely on sheep myeloid antimicrobial peptide 29, was tested in a rat model of mucoid P. aeruginosa lung infection. P. aeruginosa NH57388A, a mucoid strain isolated from a CF patient, was mixed with the alginate produced by the bacterium itself and adjusted to a concentration of 10¹⁰ CFU/ml. Each rat received 10⁹ CFU of bacteria intratracheally in the left lung to establish lung infection. At 0 and 3 h post P. aeruginosa infection, the treated group of rats received novispirin G10 (0.1 mg/ml, 0.1 ml/rat) intratracheally, whereas the control group received vehicle treatment only. The animals were sacrificed on days 3, 5, 7, and 10 after challenge for evaluation of various parameters. On day 5, 50% of the rats in the treated group had cleared the bacteria from the lungs, whereas in the control group, none of the rats cleared the pathogen (P < 0.03). The average bacterial loads remaining in the lungs of treated rats on days 3 and 5 were more than 170- and 330-fold lower than in the control groups (P < 0.0005 and P < 0.0003). In accordance, the macroscopic and microscopic lung pathology was also significantly milder in the treated group compared to the control group (P < 0.0002). Lung cytokine responses in the treated group were significantly lower than in the control group. The results suggest that novispirin G10 might be useful in treating antibiotic-resistant P. aeruginosa lung infections.

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* Corresponding author. Mailing address: Department of Clinical Microbiology, Afsnit 9301, University Hospital of Copenhagen, Rigshospitalet, Juliane Maries Vej 22, DK-2100 Copenhagen Ø, Denmark. Phone: 45-35456469. Fax: 45-35456412. E-mail: zhijun.song{at}rh.dk.

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Antimicrobial Agents and Chemotherapy, September 2005, p. 3868-3874, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3868-3874.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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