Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria.

Ceftazidime and cefotaxime are β-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 β-lactamases (ESBLs) were also investigated. Morphological changes after exposure to the β-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. [ABSTRACT FROM AUTHOR]