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 Pevear, D. C.
Right arrow Articles by Collett, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pevear, D. C.
Right arrow Articles by Collett, M. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2005, p. 4492-4499, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4492-4499.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Relationship of Pleconaril Susceptibility and Clinical Outcomes in Treatment of Common Colds Caused by Rhinoviruses

Daniel C. Pevear,1* Frederick G. Hayden,2 Tina M. Demenczuk,1,{dagger} Linda R. Barone,1,{ddagger} Mark A. McKinlay,1,§ and Marc S. Collett1,¶

ViroPharma Incorporated, Exton, Pennsylvania 19341,1 University of Virginia School of Medicine, Charlottesville, Virginia 229012

Received 12 April 2005/ Returned for modification 14 June 2005/ Accepted 21 July 2005

Pleconaril, a specific inhibitor of human picornaviruses, showed therapeutic efficacy against community-acquired colds caused by rhinoviruses in two placebo-controlled trials. Virological assessments were conducted during these trails, including virus culture and drug susceptibility testing. Nasal mucus samples collected from the enrolled patients were tested for the presence of picornavirus by reverse transcriptase PCR and culture. In total, 827 baseline nasal mucus samples were positive by virus culture (420 in the placebo group and 407 in the pleconaril group). Pleconaril treatment was associated with a more rapid loss of culturable virus. By study day 3, the number of samples positive by culture fell to 282 for the placebo-treated subjects and 202 for the pleconaril-treated subjects (P < 0.0001); and by day 6, the number of samples in the two groups positive by culture fell to 196 and 165, respectively (P = 0.07). The clinical benefit correlated strongly with the pleconaril susceptibility of the baseline virus isolate. Pleconaril-treated subjects infected with the more highly susceptible viruses (50% effective concentration ≤ 0.38 µg/ml) experienced a median 1.9- to 3.9-day reduction in symptom duration compared with that for the placebo-treated subjects. By contrast, subjects whose baseline virus isolate susceptibility was >0.38 µg/ml did not benefit from pleconaril treatment. These results indicate that the magnitude of symptomatic improvement in pleconaril-treated subjects with community-acquired colds is related to the drug susceptibility of the infecting virus, clearly linking the antiviral effects of the drug to clinical efficacy. Postbaseline virus isolates with reduced susceptibility or full resistance to pleconaril were recovered from 10.7% and 2.7% of drug-treated subjects, respectively. These patients shed low levels of virus and had no unusual clinical outcomes. Nevertheless, studies on the biologic properties and transmissibility of these variant viruses are warranted.

* Corresponding author. Present address: Progenics Pharmaceuticals Incorporated, 777 Old Saw Mill River Road, Tarrytown, NY 10591. Phone: (914) 784-1079. Fax: (914) 789-2807. E-mail: dpevear{at}progenics.com.

{dagger} Present address: New Hope, Pa.

{ddagger} Present address: AstraZeneca Pharmaceuticals, Wilmington, Del.

§ Present address: Gentara Corporation, Malvern, Pa.

Present address: Washington, D.C.

Antimicrobial Agents and Chemotherapy, November 2005, p. 4492-4499, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4492-4499.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nichols, W. G., Peck Campbell, A. J., Boeckh, M. (2008). Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances. Clin. Microbiol. Rev. 21: 274-290 [Abstract] [Full Text]  
  • Jennings, L C, Anderson, T P, Beynon, K A, Chua, A, Laing, R T R, Werno, A M, Young, S A, Chambers, S T, Murdoch, D R (2008). Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax 63: 42-48 [Abstract] [Full Text]  
  • Martinez, F. J. (2007). Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 4: 647-658 [Abstract] [Full Text]  
  • Binford, S. L., Weady, P. T., Maldonado, F., Brothers, M. A., Matthews, D. A., Patick, A. K. (2007). In Vitro Resistance Study of Rupintrivir, a Novel Inhibitor of Human Rhinovirus 3C Protease. Antimicrob. Agents Chemother. 51: 4366-4373 [Abstract] [Full Text]  
  • Kaiser, L., Aubert, J.-D., Pache, J.-C., Deffernez, C., Rochat, T., Garbino, J., Wunderli, W., Meylan, P., Yerly, S., Perrin, L., Letovanec, I., Nicod, L., Tapparel, C., Soccal, P. M. (2006). Chronic Rhinoviral Infection in Lung Transplant Recipients. Am. J. Respir. Crit. Care Med. 174: 1392-1399 [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»