Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106011
Title: High β-lactamase levels change the pharmacodynamics of β-lactam antibiotics in pseudomonas aeruginosa biofilms
Authors: Wang, Hengzhuang
Ciofu, Oana
Yang, Liang
Wu, Hong
Song, Zhijun
Oliver, Antonio
Høiby, Niels
Keywords: DRNTU::Science::Biological sciences::Microbiology
Issue Date: 2013
Source: Wang, H., Ciofu, O., Yang, L., Wu, H., Song, Z., Oliver, A., et al. (2013). High β-lactamase levels change the pharmacodynamics of β-lactam antibiotics in pseudomonas aeruginosa biofilms. Antimicrobial agents and chemotherapy, 57(1), 196-204.
Series/Report no.: Antimicrobial agents and chemotherapy
Abstract: Resistance to β-lactam antibiotics is a frequent problem in Pseudomonas aeruginosa lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded β-lactamase and biofilm formation. The purpose of this study was to investigate the role of β-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on P. aeruginosa biofilms. P. aeruginosa PAO1 and its corresponding β-lactamase-overproducing mutant, PAΔDDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers, microtiter plates, and on alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on the biofilms was investigated in vitro by time-kill methods. Time-dependent killing of ceftazidime was observed in PAO1 biofilms, but concentration-dependent killing activity of ceftazidime was observed for β-lactamase-overproducing biofilms of P. aeruginosa in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PAΔDDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of β-lactamase, which can hydrolyze the β-lactam antibiotics. The PK/PD indices of the AUC/MBIC and Cmax/MBIC (AUC is the area under concentration-time curve, MBIC is the minimal biofilm-inhibitory concentration, and Cmax is the maximum concentration of drug in serum) are probably the best parameters to describe the effect of ceftazidime in β-lactamase-overproducing P. aeruginosa biofilms. Meanwhile, imipenem showed time-dependent killing on both PAO1 and PAΔDDh2Dh3 biofilms. An inoculum effect of β-lactams was found for both planktonic and biofilm P. aeruginosa cells. The inoculum effect of ceftazidime for the β-lactamase-overproducing mutant PAΔDDh2Dh3 biofilms was more obvious than for PAO1 biofilms, with a requirement of higher antibiotic concentration and a longer period of treatment.
URI: https://hdl.handle.net/10356/106011
http://hdl.handle.net/10220/26343
ISSN: 0066-4804
DOI: 10.1128/AAC.01393-12
Rights: © 2013 American Society for Microbiology. This paper was published in Antimicrobial Agents and Chemotherapy and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The published version is available at: [http://dx.doi.org/10.1128/AAC.01393-12]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCELSE Journal Articles

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