Antipneumococcal activity of ABT-773 compared to those of 10 other agents.
MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC(50), 0.06 microgram/ml; MIC(90), 0.125 microgram/ml). Activities of pristinamycin (MIC(90), 0.5 microgram/ml) and vancomycin (MIC(90), 0.25 microgram/ml) were unaffected by macrolide or penicillin resistance, while beta-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 microgram/ml, while macrolide and azalide MICs were all >/=16.0 microgram/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 microgram/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or beta-lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.
Davies
T A
TA
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Ednie
L M
LM
Hoellman
D M
DM
Pankuch
G A
GA
Jacobs
M R
MR
Appelbaum
P C
PC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048628:Ketolides; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D048628:Ketolides; D004917:Erythromycin; C405499:cethromycin