Differential distributions in tissues and efficacies of aztreonam and ceftazidime and in vivo bacterial morphological changes following treatment.
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 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.
Turcotte
A
A
Centre de Recherche en Infectiologie, Centre Hospitalier, de l'Université Laval, Ste.-Foy, Quebec, Canada.
Simard
M
M
Morin
N J
NJ
Beauchamp
D
D
Bergeron
M G
MG
D000818:Animals; D001398:Aztreonam / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000648:ultrastructure; D004756:Enterobacteriaceae Infections / Q000097:blood / Q000188:drug therapy; D005260:Female; D005337:Fibrin; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits; D016868:Serratia Infections / Q000097:blood / Q000188:drug therapy; D012706:Serratia marcescens / Q000187:drug effects* / Q000648:ultrastructure
D002511:Cephalosporins; D008997:Monobactams; D005337:Fibrin; D002442:Ceftazidime; D001398:Aztreonam