2012年12月2日 訊 /生物谷BIOON/ --近日,，刊登在國際雜志Antimicrobial Agents and Chemotherapy上的一篇研究報告中，來自哥本哈根大學醫(yī)學院的研究者揭示了綠膿桿菌中,，高水平的β-內(nèi)酰胺酶可以高效改變β-內(nèi)酰胺類抗生素的活性,。
該項研究以標題“High beta-lactamase levels change the pharmacodynamics of beta-lactam antibiotics in Pseudomonas aeruginosa biofilms” 刊登于該雜志10月刊上。相關(guān)研究對于理解細菌對于抗生素的耐藥性以及開發(fā)新型抗生素有一定幫助。
在綠膿桿菌感染的肺部纖維化囊腫病人身上,，細菌對β-內(nèi)酰胺類抗生素的抗性普遍存在,，這種耐藥性主要取決于細菌染色體編碼的β-內(nèi)酰胺酶的產(chǎn)生以及細菌生物被膜的產(chǎn)生。
研究者Niels Hoiby表示,，他們開展這項研究的目的在于研究抗生素頭孢他啶及亞胺培南作為β-內(nèi)酰胺類抗生素在對于綠膿桿菌的生物被膜形成的影響,、藥代動力學以及藥效學。
在文章中,，研究者使用野生型菌株P(guān)AO1以及β內(nèi)酰胺酶過量產(chǎn)生的突變體菌株P(guān)AΔDDh2Dh3進行實驗研究,，研究者用不同濃度的頭孢他啶及亞胺培南作用于兩種菌株，并且觀察其生物被膜的產(chǎn)生量,。結(jié)果顯示,，頭孢他啶在殺滅野生型細菌和突變體菌株上表現(xiàn)出時間依賴性，而亞胺培南在抑制野生型菌株和突變體菌株生成生物被膜上表現(xiàn)出事件依賴性,。
而β內(nèi)酰胺酶的接種效應(yīng)在綠膿桿菌的浮游菌株和生物被膜都有發(fā)現(xiàn),，而頭孢他啶對于
突變體菌株P(guān)AΔDDh2Dh3的效應(yīng)比對野生型PAO1的效應(yīng)更為明顯。相關(guān)的研究為研究者揭示細菌對抗生素產(chǎn)生耐藥性以及開發(fā)新型抵御細菌感染的抗生素提供了希望和幫助,。（生物谷Bioon.com）
doi:10.1128/AAC.01393-12
PMC:
PMID:
High beta-lactamase levels change the pharmacodynamics of beta-lactam antibiotics in Pseudomonas aeruginosa biofilms
Wang Hengzhuang1↴, Oana Ciofu2, Liang Yang3,5, Hong Wu1,2,5, Zhijun Song1, Antonio Oliver4 and Niels Høiby1,2,6
Resistance to β-lactam antibiotics is a frequent problem in P. aeruginosa lung infection of cystic fibrosis (CF). This resistance is mainly due to the hyper-production of chromosomally encoded β-lactamase and biofilm formation. The purpose of this study was to investigate the role of β-lactamase in the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ceftazidime and imipenem on P. aeruginosa biofilms. PAO1 and its corresponding β-lactamase-overproducing mutant PAΔDDh2Dh3 were used in this study. Biofilms of these two strains in flow-chamber, microtiter-plate, and alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on 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 the three models. Ceftazidime showed time-dependent killing on both planktonic PAO1 and PAΔDDh2Dh3. This difference is probably due to the special distribution and accumulation of β-lactamase in the biofilm matrix which can hydrolyze the β-lactam antibiotics. The PK/PD indices of AUC/MBIC and Cmax/MBIC (AUC, area under curve; Cmax, maximum concentration; MBIC, minimal biofilm inhibitory concentration) are probably best 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. Inoculum effect of β-lactams was found in both planktonic and biofilm P. aeruginosa. The inoculum effect of ceftazidime for β-lactamase-overproducing mutant PAΔDDh2Dh3 biofilms was more obvious than PAO1 biofilms with the requirement of higher antibiotic concentration and longer period treatment.
