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Infection and Immunity, November 2003, p. 6199-6204, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6199-6204.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia

Jutta M. Loeffler,1 Svetolik Djurkovic,2 and Vincent A. Fischetti1*

Laboratory of Bacterial Pathogenesis, The Rockefeller University,1 Division of Infectious Disease, Sloan-Kettering Cancer Institute, New York, New York 100212

Received 6 May 2003/ Returned for modification 17 July 2003/ Accepted 5 August 2003

Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide, and thus new antimicrobials are badly needed. We report the use of Cpl-1, the lytic enzyme of a pneumococcal bacteriophage, as an intravenous therapy for pneumococcal bacteremia in a mouse model. A 2,000-µg dose of Cpl-1 reduced pneumococcal titers from a median of log10 4.70 CFU/ml to undetectable levels (<log10 2.00 CFU/ml) within 15 min. This dose given 1 h after intravenous infection led to 100% survival at 48 h, compared to the 20% survival of buffer-treated controls. In advanced bacteremia, treatment with two doses at 5 and 10 h still resulted in significantly longer survival (P < 0.0001) and a hazard ratio of 0.29 (95% confidence interval, 0.04 to 0.35). The enzyme is immunogenic, but the treatment efficacy was not significantly diminished after previous intravenous exposure of mice and hyperimmune rabbit serum did not neutralize the activity. Cpl-1 is also very effective as a topical nasal treatment against colonization by S. pneumoniae. In vitro, the enzyme is active against many serotypes of S. pneumoniae, independent of their penicillin resistance, and it is very specific for this species. Bacteriophage enzymes are unusual but extremely effective antimicrobials and represent a new weapon against infections with resistant bacteria.

* Corresponding author. Mailing address: Laboratory of Bacterial Pathogenesis, The Rockefeller University, 1230 York Avenue, New York, NY 10021. Phone: (212) 327-8166. Fax: (212) 327-7584. E-mail: vaf{at}rockefeller.edu.

Editor: J. N. Weiser

Infection and Immunity, November 2003, p. 6199-6204, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6199-6204.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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