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 (telithromy cin), and the comparator agents erythromycin A, azithromycin, clarithromyci n, roxithromycin, levofloxacin, ofloxacin and penicillin G were determined by an agar dilution method against 410 isolates of Corynebacterium diphther iae. Test isolates originated from diverse geographical locations, includin g the former USSR, where epidemic diphtheria has re-emerged during the 1990 s. All isolates tested were susceptible to penicillin G, ofloxacin and levo floxacin. The two ketolides and four macrolides were highly active against 405 of the 410 isolates. HMR 3004 was the most active of the drugs, followe d by HMR 3647, clarithromycin, erythromycin A, roxithromycin and azithromyc in. Five isolates showed reduced susceptibility to all macrolides and ketol ides tested; three were non-toxigenic isolates from Australia and the remai ning two were from cases of diphtheria in Vietnam. Inducible (MLSB) resista nce was detected in the isolates from Vietnam, but not in the isolates orig inating from Australia. Significant antimicrobial resistance remains rare a mongst C. diphtheriae; nevertheless, new ketolide antimicrobials may have a role to play in the treatment and control of this re-emergent pathogen.