Relationship between the bactericidal and bacteriolytic activity of cephalosporins and changes in the cell volumes of Escherichia coli cultures.

The bactericidal effect of cefoxitin and cefotaxime in relation to concentration and exposure time, as demonstrated by the killing curve diagrams of Escherichia coli cultures, was compared with the degree of bacteriolysis and the cell volume increase measured by the coulter counter-channel analyser system. Human plasma ultrafiltrate was used as the growth medium. Cefoxitin has a higher bactericidal activity than cefotaxime. With increasing concentrations the bactericidal efficacy of cefoxitin increases more rapidly in the lower range of concentrations (2-10 mg/l) than in the higher range (10-40 mg/l). In contrast, the bactericidal effect of cefotaxime in the range 0.06-1.2 mg/l is virtually constant and can only be increased by high levels (10-40 mg/l). The morphometric effect of cefoxitin on E. coli cultures, as demonstrated by volume distribution curves, is characterized by intensive and rapidly appearing bacteriolysis 20 min after exposure to the antibiotic without a preceding increase in bacterial cell volume. Higher concentrations result in an earlier onset of bacteriolysis. In contrast, the application of cefotaxime reveals a massive increase in bacterial cell volume (more than five-fold) with a delayed (greater than 2 h) onset of bacteriolysis. High cefotaxime concentrations reduce the extent of bacterial cell volume increase, associated with an earlier and more intensive onset of bacteriolysis. With both cephalosporins, the bacterial cell alterations are particularly dependent on the exposure time. There is evidently a close correlation between bactericidal and bacteriolytic activity. This is valid both for the two cephalosporins and generally for the concentration-activity relationships.