Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria
Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria
复制标题
DOI：
10.1111/j.1469-0691.2007.01940.x
复制
发表时间：
2008-04-01
影响因子：
14.2
通讯作者：
van der Meer, J. W. M.
中科院分区：
文献类型：
--
作者：
Buijs, J.;Dofferhoff, A. S. M.;van der Meer, J. W. M.
头孢他啶和头孢噻肟是β-内酰胺类抗生素，对青霉素结合蛋白（PBP）-3和PBP-1具有剂量相关的亲和力。在低浓度下，这些抗生素抑制PBP-3，导致细丝形成。丝状体是含有大量内毒素分子的非分裂细菌的长链。较高浓度的头孢他啶或头孢噻肟引起PBP-1的抑制，导致快速细菌溶解，这与低内毒素释放相关。在本研究中，37株大肠埃希菌，克雷伯菌属，铜绿假单胞菌和不动杆菌属。在8种浓度的头孢他啶或头孢噻肟存在下，在4小时孵育期内进行研究。由于革兰氏阴性菌的耐药性是临床实践中新出现的问题，14株大肠杆菌分离株。大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶（ESBLs）。暴露于β-内酰胺类抗生素后的形态学变化揭示了各种细菌科、属和分离株的可识别模式。总的来说，所有肠杆菌科分离株在相对较小的浓度范围内产生丝状体，E.埃希菌和肺炎。假单胞菌属和不动杆菌属。在两种抗生素的临床相关浓度高达50 mg/L的情况下产生细丝。在所有属中，产毒能力与MIC明显相关。头孢他啶比头孢噻肟在更多的菌株和更宽的浓度范围内诱导丝状体产生。有趣的是，产ESBL的分离株不受丝状诱导的保护。在严重感染的经验性治疗期间，细丝产生的诱导可能导致额外的风险。
Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quantities of endotoxin molecules. Higher concentrations of ceftazidime or cefotaxime cause inhibition of PBP-1, resulting in rapid bacterial lysis, which is associated with low endotoxin release. In the present study, 37 isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. were studied over a 4-h incubation period in the presence of eight concentrations of ceftazidime or cefotaxime. As resistance of Gram-negative bacteria is an emerging problem in clinical practice, 14 isolates of E. coli and Klebsiella pneumoniae that produced extended-spectrum beta-lactamases (ESBLs) were also investigated. Morphological changes after exposure to the beta-lactam antibiotics revealed recognisable patterns in various bacterial families, genera and isolates. In general, all isolates of Enterobacteriaceae produced filaments within a relatively small concentration range, with similar patterns for E. coli and K. pneumoniae. Pseudomonas and Acinetobacter spp. produced filaments in the presence of clinically-relevant concentrations of both antibiotics as high as 50 mg/L. In all genera, filament-producing capacity was clearly related to the MIC. Ceftazidime induced filament production in more isolates and over wider concentration ranges than did cefotaxime. Interestingly, ESBL-producing isolates were not protected against filament induction. The induction of filament production may lead to additional risks during empirical treatment of severe infections.