Autolysis of methicillin-resistant Staphylococcus aureus is involved in synergism between imipenem and cefotiam.

Imipenem-induced autolysis and the activity of imipenem plus cefotiam were studied in 16 strains of methicillin-resistant Staphylococcus aureus (MRSA). The degree of imipenem-induced autolysis and the rate of synergistic action of imipenem plus cefotiam varied among strains and did not correlate with susceptibility to either imipenem or cefotiam. However, the degree of autolysis correlated well with susceptibility to the synergistic action of imipenem plus cefotiam. In methicillin-susceptible S. aureus strains, both imipenem-induced autolysis and the synergistic activity of the combined drugs were less than those observed in MRSA strains. Differences in the degree of autolysis were not due to differences in autolytic enzyme production. The autolysis of imipenem-pretreated MRSA was enhanced further by cefotiam, while treatment of cells in the reverse order did not enhance autolysis. These findings indicate that cell wall impairment in MRSA is caused by exposure to imipenem but not to cefotiam and that this difference in drug actions results in synergism between imipenem and cefotiam. The possible participation of penicillin-binding proteins PBP 2' and PBP4 in the observed effect is discussed.