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 Bakker-Woudenberg, I. A. J. M.
Right arrow Articles by Mouton, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bakker-Woudenberg, I. A. J. M.
Right arrow Articles by Mouton, J. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2002, p. 2575-2581, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2575-2581.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection

Irma A. J. M. Bakker-Woudenberg,1* Marian T. ten Kate,1 Luke Guo,2 Peter Working,2 and Johan W. Mouton1,3

Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam,1 Department of Medical Microbiology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands,3 ALZA Corporation, Mountain View, California2

Received 14 June 2001/ Returned for modification 26 December 2001/ Accepted 25 April 2002

In a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal ciprofloxacin in high doses was nontoxic and resulted in relatively high and sustained ciprofloxacin concentrations in blood and tissues, and hence an increase in the area under the plasma concentration-time curve (AUC). These data correspond to data from animal and clinical studies showing that for fluoroquinolones the AUC/MIC ratio is associated with favorable outcome in serious infections. Clinical failures and the development of resistance are observed for marginally susceptible organisms like Pseudomonas aeruginosa and for which sufficient AUC/MIC ratios cannot be achieved. In the present study the therapeutic efficacy of pegylated liposomal ciprofloxacin was investigated in two rat models of Pseudomonas aeruginosa pneumonia. In the acute model pneumonia developed progressively, resulting in a rapid onset of septicemia and a high mortality rate. Ciprofloxacin twice daily for 7 days was not effective at doses at or below the maximum tolerated dose (MTD). However, pegylated liposomal ciprofloxacin either at high dosage or given at low dosage in combination with free ciprofloxacin on the first day of treatment was fully effective (100% survival). Obviously, prolonged concentrations of ciprofloxacin in blood prevented death of the animals due to early-stage septicemia in this acute infection. However, bacterial eradication from the left lung was not effected. In the chronic model, pneumonia was characterized by bacterial persistence in the lung without bacteremia, and no signs of morbidity or mortality were observed. Ciprofloxacin administered for 7 days at the MTD twice daily resulted in killing of more than 99% of bacteria in the lung; this result can also be achieved with pegylated liposomal ciprofloxacin given once daily. Complete bacterial eradication is never observed.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31 10 4087666. Fax: 31 10 4089454. E-mail: bakker{at}kmic.fgg.eur.nl.

Antimicrobial Agents and Chemotherapy, August 2002, p. 2575-2581, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2575-2581.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Oldak, E., Trafny, E. A. (2005). Secretion of Proteases by Pseudomonas aeruginosa Biofilms Exposed to Ciprofloxacin. Antimicrob. Agents Chemother. 49: 3281-3288 [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»