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 Piroth, L.
Right arrow Articles by Chavanet, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Piroth, L.
Right arrow Articles by Chavanet, P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 1999, p. 2484-2492, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Development of a New Experimental Model of Penicillin-Resistant Streptococcus pneumoniae Pneumonia and Amoxicillin Treatment by Reproducing Human Pharmacokinetics

Lionel Piroth,1 Laurent Martin,2 Alexis Coulon,1 Catherine Lequeu,1 Michel Duong,1 Marielle Buisson,1 Henri Portier,1 and Pascal Chavanet1,*

Service des Maladies Infectieuses et Tropicales, Microbiologie Médicale et Moléculaire (EA562), Hôpital du Bocage,1 and Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Dijon,2 Dijon Cedex, France

Received 25 September 1998/Returned for modification 20 February 1999/Accepted 16 June 1999

The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log10 CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log10 CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log10 CFU/ml, P < 10-6) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.

* Corresponding author. Mailing address: Service des Maladies Infectieuses et Tropicales, Hôpital du Bocage, BP 1542, 21034 Dijon Cedex, France. Phone: (33) 3 80 29 36 37. Fax: (33) 3 80 29 36 38. E-mail: p.chavanet{at}planetb.fr.

Antimicrobial Agents and Chemotherapy, October 1999, p. 2484-2492, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chiavolini, D., Pozzi, G., Ricci, S. (2008). Animal Models of Streptococcus pneumoniae Disease. Clin. Microbiol. Rev. 21: 666-685 [Abstract] [Full Text]  
  • Abgueguen, P., Azoulay-Dupuis, E., Noel, V., Moine, P., Rieux, V., Fantin, B., Bedos, J.-P. (2007). Amoxicillin Is Effective against Penicillin-Resistant Streptococcus pneumoniae Strains in a Mouse Pneumonia Model Simulating Human Pharmacokinetics. Antimicrob. Agents Chemother. 51: 208-214 [Abstract] [Full Text]  
  • Yershov, A. L., Jordan, B. S., Guymon, C. H., Dubick, M. A. (2005). Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model. Eur Respir J 25: 693-700 [Abstract] [Full Text]  
  • Pelton, S. I., Hammerschlag, M. R. (2005). Overcoming Current Obstacles in the Management of Bacterial Community-Acquired Pneumonia in Ambulatory Children. CLIN PEDIATR 44: 1-17  
  • Croisier, D., Etienne, M., Piroth, L., Bergoin, E., Lequeu, C., Portier, H., Chavanet, P. (2004). In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants. J Antimicrob Chemother 54: 640-647 [Abstract] [Full Text]  
  • Croisier, D., Etienne, M., Bergoin, E., Charles, P.-E., Lequeu, C., Piroth, L., Portier, H., Chavanet, P. (2004). Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy. Antimicrob. Agents Chemother. 48: 1699-1707 [Abstract] [Full Text]  
  • Rubinstein, E. (2003). Reply to: Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones. J Antimicrob Chemother 51: 1307-1308 [Full Text]  
  • Croisier, D., Etienne, M., Chavanet, P. (2003). Reply. J Antimicrob Chemother 51: 1308-1309 [Full Text]  
  • Croisier, D., Chavanet, P., Lequeu, C., Ahanou, A., Nierlich, A., Neuwirth, C., Piroth, L., Duong, M., Buisson, M., Portier, H. (2002). Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones. J Antimicrob Chemother 50: 349-360 [Abstract] [Full Text]  
  • Piroth, L., Desbiolles, N., Mateo-Ponce, V., Martin, L., Lequeu, C., Charles, P.-E., Portier, H., Chavanet, P. (2001). HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 47: 33-42 [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»