Differential distributions in tissues and efficacies of aztreonam and ceftazidime and in vivo bacterial morphological changes following treatment

Abstract

The differential tissue distributions of aztreonam and ceftazidime within fibrin clots infected with Pseudomonas aeruginosa, Enterobacter cloacae, and Serratia marcescens, their efficacies, and the in vivo bacterial morphological changes induced by these drugs were evaluated. Rabbits were given intravenously a single dose of 100 mg of either agents/kg of body weight. In the cores of the clots, the peak levels of both drugs were much lower than those observed in the peripheries and in serum. Aztreonam's half-lives within the peripheries and in the cores of the fibrin clots were up to six times higher than that observed in serum, while ceftazidime's half-lives in clots were twice that observed in serum. This resulted in a much greater penetration ratio for aztreonam than for ceftazidime. Both drugs controlled the growth of P. aeruginosa in vivo, but E. cloacae and S. marcescens responded better to ceftazidime. Morphological changes were more abundant in the peripheries than in the cores of the clots. In the control group, P. aeruginosa's morphology in the cores was different than that in the peripheries of the clots. Against P. aeruginosa, aztreonam did induce morphological changes in the cores while ceftazidime did not. Electron microscopic studies revealed that morphological changes associated with aztreonam seemed different than those of ceftazidime. Along with elongation of bacteria, more bow tie and herniated bacteria were observed with aztreonam. Though both agents selectively affect PBP 3, as manifested by elongated bacteria, they induce in the peripheries of the clots thickening, breaks, and detachment in bacterial cell walls, alterations which are generally associated with antibiotics affecting PBP 1a and 1b.

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

“…Each β‐lactam agent has a specific binding affinity for different PBPs. Ceftazidime and cefotaxime, which are oxyimino‐containing cephalosporins, both bind to PBP‐3 at relatively low concentrations, and to PBP‐1 at higher concentrations [2,17,18]. Reports concerning the concentrations at which specific PBP‐binding occurs are scarce [19].…”

Single Live Cell Imaging of Chromosomes in Chloramphenicol-Induced Filamentous Pseudomonas aeruginosa

“…Previous studies of filamentation have focused primarily on the changes in cellular morphology as normal cells turn to filamentous cells using electron microscopy (2,5,7,8,(10)(11)(12), X-ray micrography (6), and phase-contrast optical microscopy (5,10). However, these techniques are used to image the morphology of the dead cells, and temporal information on how antibiotics affect the replication of chromosomes in live cells cannot be obtained.…”