DIFFERENTIAL DISTRIBUTIONS IN TISSUES AND EFFICACIES OF AZTREONAM ANDCEFTAZIDIME AND IN-VIVO BACTERIAL MORPHOLOGICAL-CHANGES FOLLOWING TREATMENT

The differential tissue distributions of aztreonam and ceftazidime wit hin fibrin clots infected with Pseudomonas aeruginosa, Enterobacter cl oacae, and Serratia marcescens, their efficacies, and the in vivo bact erial morphological changes induced by these drugs were evaluated, Rab bits 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 s erum, Aztreonam's half-lives within the peripheries and in the cores o f the fibrin clots were up to six times higher than that observed in s erum, while ceftazidime's half-lives in clots were twice that observed in serum, This resulted in a much greater penetration ratio for aztre onam than for ceftazidime. Both drugs controlled the growth of P. aeru ginosa in vivo, but E. cloacae and S. marcescens responded better to c eftazidime, Morphological changes were more abundant in the peripherie s 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 o f 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 b acteria, more bow tie and herniated bacteria were observed with aztreo nam, Though both agents selectively affect PBP 3, as manifested by elo ngated bacteria, they induce in the peripheries of the clots thickenin g, breaks, and detachment in bacterial cell walls, alterations which a re generally associated with antibiotics affecting PBP 1a and 1b.