In vitro activity of ketolides HMR 3004 and HMR 3647 and seven other antimicrobial agents against Corynebacterium diphtheriae.

The in vitro activities of two ketolides, HMR 3004 and HMR 3647 (telithromycin), and the comparator agents erythromycin A, azithromycin, clarithromycin, roxithromycin, levofloxacin, ofloxacin and penicillin G were determined by an agar dilution method against 410 isolates of Corynebacterium diphtheriae. Test isolates originated from diverse geographical locations, including the former USSR, where epidemic diphtheria has re-emerged during the 1990s. All isolates tested were susceptible to penicillin G, ofloxacin and levofloxacin. The two ketolides and four macrolides were highly active against 405 of the 410 isolates. HMR 3004 was the most active of the drugs, followed by HMR 3647, clarithromycin, erythromycin A, roxithromycin and azithromycin. Five isolates showed reduced susceptibility to all macrolides and ketolides tested; three were non-toxigenic isolates from Australia and the remaining two were from cases of diphtheria in Vietnam. Inducible (MLS(B)) resistance was detected in the isolates from Vietnam, but not in the isolates originating from Australia. Significant antimicrobial resistance remains rare amongst C. diphtheriae; nevertheless, new ketolide antimicrobials may have a role to play in the treatment and control of this re-emergent pathogen.