Buijs J, Dofferhoff A S M, Mouton J W, Wagenvoort J H T, van der Meer J W M
Department of Medical Microbiology and Infectious Diseases, Atrium Medical Centre, Heerlen, The Netherlands.
Clin Microbiol Infect. 2008 Apr;14(4):344-9. doi: 10.1111/j.1469-0691.2007.01940.x. Epub 2008 Feb 5.
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.
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具有剂量相关亲和力。在低浓度时，这些抗生素抑制PBP-3，导致丝状形成。丝状是不含分裂细菌的长链，其含有增加量的内毒素分子。较高浓度的头孢他啶或头孢噻肟会抑制PBP-1，导致细菌快速裂解，这与低内毒素释放有关。在本研究中，在8种浓度的头孢他啶或头孢噻肟存在下，对37株大肠杆菌、克雷伯菌属、铜绿假单胞菌和不动杆菌属进行了4小时的培养研究。由于革兰氏阴性菌耐药性在临床实践中是一个新出现的问题，还对14株产生超广谱β-内酰胺酶（ESBLs）的大肠杆菌和肺炎克雷伯菌进行了研究。暴露于β-内酰胺类抗生素后的形态学变化揭示了不同细菌科、属和菌株中可识别的模式。一般来说，所有肠杆菌科菌株在相对较小的浓度范围内都会产生丝状，大肠杆菌和肺炎克雷伯菌的模式相似。铜绿假单胞菌和不动杆菌属在两种抗生素高达50mg/L的临床相关浓度下都会产生丝状。在所有属中，产生丝状的能力显然与最低抑菌浓度（MIC）有关。与头孢噻肟相比，头孢他啶在更多菌株和更宽浓度范围内诱导丝状产生。有趣的是，产ESBLs的菌株并不能免受丝状诱导的影响。丝状产生的诱导可能会在严重感染的经验性治疗期间导致额外风险。
