Time-kill studies on susceptibility of nine penicillin-susceptible and -resistant pneumococci to cefditoren compared with nine other beta-lactams

Broth MIC and time-kill methodology was used to determine the activity of cefditoren relative to those of penicillin G, ampicillin, amoxycillin, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime and cefaclor against three penicillin-susceptible, three intermediate and three penicillin-resistant pneumococci. MICs of all agents rose with those of penicillin G. Cefditoren was the most active agent (MICs 0.002-0.5 mg/L), followed by WY-49605 (0.008-1.0 mg/L), amoxycillin (0.015-2.0 mg/L), cefuroxime (0.015-4.0 mg/L), cefpodoxime (0.03-4.0 mg/L), ampicillin (0.015-8.0 mg/L), cefdinir (0.03-16.0 mg/L), cefixime (0.125-64.0 mg/L) and cefaclor (0.5-128.0 mg/L). All beta-lactams were bactericidal at the MIC after 24 h, and produced 90% killing after 12 h at concentrations above the MIC. Bactericidal concentrations of cefditoren, even for penicillin-resistant strains, were less than or equal to 0.5 mg/L at 24 h. Additionally, cefditoren and WY-49605 were the only compounds that killed 99% of all strains after 6 h at greater than or equal to 4 x MIC. Cefditoren and amoxycillin killed 90% of all strains at 8 x MIC, and WY-49605 at 4 x MIC, after 4 h. Ampicillin had time-kill kinetics similar to those of amoxycillin, but MICs were 1-2 dilutions higher than the latter drug. Cefuroxime and cefpodoxime were the most active of other oral cephalosporins tested. Cefditoren and WY-49605 had the lowest MICs and most favourable time-kill kinetics of all beta-lactams tested.