This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mosca, D. A.
Right arrow Articles by Falla, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mosca, D. A.
Right arrow Articles by Falla, T. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2000, p. 1803-1808, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

IB-367, a Protegrin Peptide with In Vitro and In Vivo Activities against the Microflora Associated with Oral Mucositis

Deborah A. Mosca,dagger Malinda A. Hurst, Wendy So, Beverly S. C. Viajar, Craig A. Fujii, and Timothy J. Falla*

IntraBiotics Pharmaceuticals, Inc., Mountain View, California 94043

Received 7 December 1999/Returned for modification 9 February 2000/Accepted 29 March 2000

Although the microflora associated with oral mucositis initiated by cytotoxic therapy is not well characterized, several studies suggest that reduction of the microbial load in the oral cavity has some clinical benefit. The MICs of IB-367, a synthetic protegrin analog, ranged from 0.13 to 64 µg/ml for gram-positive bacteria (Streptococcus mitis, Streptococcus sanguis, Streptococcus salivarius, and Staphylococcus aureus) and from 0.06 to 8 µg/ml for gram-negative species (Klebsiella, Escherichia, and Pseudomonas). IB-367 exhibited rapid, microbicidal activity against both log- and stationary-phase cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. At concentrations near the MICs for these two organisms (4 and 2 µg/ml, respectively), IB-367 reduced viability by more than 3 logs in less than 16 min. Similarly, IB-367 effected a 4-log reduction of the endogenous microflora in pooled human saliva within 2 min at 250 µg/ml, a concentration readily attained by local delivery. After nine serial transfers at 0.5× the MIC, the MIC of IB-367 for MRSA and P. aeruginosa increased only two to four times. In a phase I clinical study with healthy volunteers, IB-367 was well tolerated, with no detectable systemic absorption. One hour after treatment with 9 mg of IB-367, the prevalence of gram-negative bacteria and yeast was reduced, and the density of the predominant gram-positive oral flora was decreased 1,000 times. IB-367's properties (speed of killing, breadth of spectrum, and lack of resistance) make the compound a strong candidate for the prophylaxis of oral mucositis. Phase II clinical trials with IB-367 are under way for this indication in immunocompromised subjects.

* Corresponding author. IntraBiotics Pharmaceuticals, Inc., 1255 Terra Bella Ave., Mountain View, CA 94043. Phone: (650) 526-6800. Fax: (650) 969-0663. E-mail: tfalla{at}intrabiotics.com.

dagger Present address: Elitra Pharmaceuticals, San Diego, CA 92121.

Antimicrobial Agents and Chemotherapy, July 2000, p. 1803-1808, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tran, D., Tran, P., Roberts, K., Osapay, G., Schaal, J., Ouellette, A., Selsted, M. E. (2008). Microbicidal Properties and Cytocidal Selectivity of Rhesus Macaque Theta Defensins. Antimicrob. Agents Chemother. 52: 944-953 [Abstract] [Full Text]  
  • Porat, Y., Marynka, K., Tam, A., Steinberg, D., Mor, A. (2006). Acyl-Substituted Dermaseptin S4 Derivatives with Improved Bactericidal Properties, Including on Oral Microflora. Antimicrob. Agents Chemother. 50: 4153-4160 [Abstract] [Full Text]  
  • Rotem, S., Radzishevsky, I., Mor, A. (2006). Physicochemical properties that enhance discriminative antibacterial activity of short dermaseptin derivatives.. Antimicrob. Agents Chemother. 50: 2666-2672 [Abstract] [Full Text]  
  • Zhu, J., Luther, P. W., Leng, Q., Mixson, A. J. (2006). Synthetic histidine-rich peptides inhibit Candida species and other fungi in vitro: role of endocytosis and treatment implications.. Antimicrob. Agents Chemother. 50: 2797-2805 [Abstract] [Full Text]  
  • Kollef, M., Pittet, D., Sanchez Garcia, M., Chastre, J., Fagon, J.-Y., Bonten, M., Hyzy, R., Fleming, T. R., Fuchs, H., Bellm, L., Mercat, A., Manez, R., Martinez, A., Eggimann, P., Daguerre, M., Charles-Edouard Luyt, for the Prevention of Pneumo, (2006). A Randomized Double-Blind Trial of Iseganan in Prevention of Ventilator-associated Pneumonia. Am. J. Respir. Crit. Care Med. 173: 91-97 [Abstract] [Full Text]  
  • Maisetta, G., Batoni, G., Esin, S., Raco, G., Bottai, D., Favilli, F., Florio, W., Campa, M. (2005). Susceptibility of Streptococcus mutans and Actinobacillus actinomycetemcomitans to Bactericidal Activity of Human {beta}-Defensin 3 in Biological Fluids. Antimicrob. Agents Chemother. 49: 1245-1248 [Abstract] [Full Text]  
  • Concannon, S. P., Crowe, T. D., Abercrombie, J. J., Molina, C. M., Hou, P., Sukumaran, D. K., Raj, P. A., Leung, K. -P. (2003). Susceptibility of oral bacteria to an antimicrobial decapeptide. J Med Microbiol 52: 1083-1093 [Abstract] [Full Text]  
  • Jang, W. S., Kim, C. H., Kim, K. N., Park, S. Y., Lee, J. H., Son, S. M., Lee, I. H. (2003). Biological Activities of Synthetic Analogs of Halocidin, an Antimicrobial Peptide from the Tunicate Halocynthia aurantium. Antimicrob. Agents Chemother. 47: 2481-2486 [Abstract] [Full Text]  
  • Giacometti, A, Cirioni, O, Ghiselli, R, Mocchegiani, F, D'Amato, G, Del Prete, M S., Orlando, F, Kamysz, W, Lukasiak, J, Saba, V, Scalise, G (2003). Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats. Gut 52: 874-878 [Abstract] [Full Text]  
  • Nagaoka, I., Hirota, S., Niyonsaba, F., Hirata, M., Adachi, Y., Tamura, H., Tanaka, S., Heumann, D. (2002). Augmentation of the Lipopolysaccharide-Neutralizing Activities of Human Cathelicidin CAP18/LL-37-Derived Antimicrobial Peptides by Replacement with Hydrophobic and Cationic Amino Acid Residues. CVI 9: 972-982 [Abstract] [Full Text]  
  • Yau, Y. H., Ho, B., Tan, N. S., Ng, M. L., Ding, J. L. (2001). High Therapeutic Index of Factor C Sushi Peptides: Potent Antimicrobials against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 45: 2820-2825 [Abstract] [Full Text]  
  • McCoy, A. J., Liu, H., Falla, T. J., Gunn, J. S. (2001). Identification of Proteus mirabilis Mutants with Increased Sensitivity to Antimicrobial Peptides. Antimicrob. Agents Chemother. 45: 2030-2037 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»