A morphological study of the effect of treatment with the antibiotic ceftazidime on experimental staphylococcal endocarditis and aortitis.

The morphological effects of antibiotic therapy with either single or repeated (8 hourly) injections of ceftazidime were examined in rabbits with experimentally induced staphylococcal endocarditis and aortitis. At 3 h after initiating treatment, many of the bacteria, irrespective of the location of the colony, showed evidence of abnormal ultrastructural changes of the cytoplasm and/or cell wall. By 8 h many degenerate lysed bacteria were present. By 24 h, in rabbits which received a single injection, bacterial colonies contained many normal and dividing bacteria. In comparison, bacterial colonies at 24 h in rabbits receiving repeated injections consisted of large masses of lysed bacteria with only a few viable appearing thick-walled 'persistent' cells. At 48 and 72 h, no viable appearing bacteria were observed although they could be isolated by culture methods. Treatment was associated with an increased inflammatory cell response at the surface of the vegetation and within the vasculature. In the later stages there was evidence of healing with endothelialization of the lesions. It would appear, therefore, that ceftazidime penetrates efficiently into the vegetations with only a short transitory phase at sub-bactericidal concentrations. The few 'persistent' bacteria appear to be protected from the host defences by the surrounding thrombus which prevents their eradication.