This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ba, B. B. Articles by Quentin, C. Search for Related Content PubMed PubMed Citation Articles by Ba, B. B. Articles by Quentin, C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2004, p. 946-953, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.946-953.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activities of Ciprofloxacin and Moxifloxacin against Stenotrophomonas maltophilia and Emergence of Resistant Mutants in an In Vitro Pharmacokinetic-Pharmacodynamic Model

Laboratoire de Pharmacocinétique et de Pharmacie Clinique,¹ Laboratoire de Microbiologie, Faculté de Pharmacie, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France²

Received 20 August 2003/ Returned for modification 12 July 2003/ Accepted 15 November 2003

A two-compartment in vitro pharmacokinetic-pharmacodynamic model, with full computer-controlled devices, was used to accurately simulate human plasma pharmacokinetic profiles after multidose oral regimens of ciprofloxacin (750 mg every 12 h) and moxifloxacin (400 mg every 24 h) during 48 h. Pharmacodynamics of these drugs was investigated against three quinolone-susceptible strains of Stenotrophomonas maltophilia (MICs of ciprofloxacin and moxifloxacin of 0.5 to 2 and 0.0625 to 0.5 µg/ml, respectively). The first dose of ciprofloxacin and moxifloxacin reduced the bacterial count by 1 and 2 log CFU/ml, respectively, prior to a bacterial regrowth that reached the plateau value of the growth control curve at 13 to 24 h versus 24 to 36 h and persisted despite repeated administration of both drugs. The surviving bacterial cells were quinolone-resistant mutants (2 to 128 times the MIC) that exhibited cross-resistance to unrelated antibiotics. Their antibiotic resistance probably resulted from the overproduction of different multidrug resistance efflux system(s). C_max/MIC and area under the concentration-time curve from 0 to 24 h (AUC_0-24)/MIC values were at least threefold higher for moxifloxacin than for ciprofloxacin. Moreover, integral parameters of ciprofloxacin and moxifloxacin, in particular the area under the killing and regrowth curve from 0 to 48 h (AUBC_0-48, 342.3 to 401.3 versus 295.2 to 378.7 h x log CFU/ml, respectively) and the area between the control growth curve and the killing and regrowth curve from 0 to 48 h (ABBC_0-48, 40.4 to 101.1 versus 72.9 to 144.7 h x log CFU/ml, respectively), demonstrated a better antibacterial effect of moxifloxacin than ciprofloxacin on S. maltophilia. However, selection of resistant mutants by both fluoroquinolones, although delayed with moxifloxacin, emphasizes the need to use maximal dosages and combined therapy in the treatment of systemic S. maltophilia infections.

This article has been cited by other articles:

• Falagas, M. E., Valkimadi, P.-E., Huang, Y.-T., Matthaiou, D. K., Hsueh, P.-R. (2008). Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review. J Antimicrob Chemother 0: dkn301v1-6 [Abstract] [Full Text]  
• Poole, K. (2005). Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56: 20-51 [Abstract] [Full Text]