Mode of action of ceftazidime: affinity for the penicillin-binding proteins of Escherichia coli K12, Pseudomonas aeruginosa and Staphylococcus aureus

Abstract

The competition of a new aminothiazolyl cephalosporin, ceftazidime, for the penicillin-binding proteins (PBP's) of Escherichia coli K12, Pseudomonas aeruginosa and Staphylococcus aureus has been studied. Ceftazidime caused filamentation and eventually cell lysis of both E. coli and Ps. aeruginosa at its minimum inhibitory concentration, due to its primary activity against PBP-3. The antibiotic also inhibited PBP's 1 a and 1 bs, the 'essential' cell elongation proteins at higher, therapeutically achievable concentrations and consequently induced rapid lysis of both E. coli and Ps. aeruginosa. In Staph. aureus ceftazidime showed high affinity for PBP-1, -2 and less affinity for PBP-3. The results indicate that in E. coli K12 and Ps. aeruginosa, ceftazidime owes its good antibacterial activity to high affinity for PBP-3, the 'essential' binding protein involved in cell division combined with favourable outer membrane penetration.