In vitro activity of the investigational ketolide cethromycin against macrolide- and penicillin-resistant Streptococcus pneumoniae: review of the 1998 to 2006 Canadian Respiratory Organism Susceptibility Study (CROSS)

Sir, Ketolides are a family of macrolide–lincosamide–streptogramin B (‘MLSB’) antimicrobials that were mainly developed to overcome macrolide resistance in pneumococci and are an attractive alternative for the treatment of respiratory tract infections in areas with significant macrolide resistance.1,2 Telithromycin's pharmacodynamic/pharmacokinetic properties suggest optimal efficacy for isolates with MICs of ≤0.25 mg/L.2 Telithromycin was the first member of this new class approved for clinical use with indications for community-acquired pneumonia (CAP).3 Telithromycin usage has, however, been limited due to worries regarding hepatotoxicity.3 Cethromycin is an investigational ketolide, currently in Phase III development, and recently a New Drug Application (NDA) has been submitted to the FDA for a CAP indication.3 During the 1998–2006 national Canadian Respiratory Organism Susceptibility Study (CROSS), we assessed the activity of cethromycin against 9398 Streptococcus pneumoniae. Here, we present the results from that study comparing the activity of cethromycin with that of telithromycin against macrolide- and penicillin-susceptible and resistant isolates as well as assessing the effect of the type of macrolide resistance, mef(A) and erm(B), on cethromycin's activity. Twenty-five medical centres in 9 of 10 Canadian provinces participated in CROSS during the 9 years.4 Consecutive respiratory tract isolates, one per patient, were identified by a conventional methodology by individual laboratories.4 All isolates were shipped to a central laboratory (Health Sciences Centre, Winnipeg, Manitoba, Canada) on Amies charcoal swabs and their identities were confirmed according to CLSI (formerly NCCLS) (2002) guidelines. Antibiotic susceptibilities were determined using the CLSI M7-A7 (2006) microbroth dilution method. MICs were interpreted according to the CLSI breakpoints (M100-S17, 2007). A total of 1289 erythromycin-resistant (MIC ≥1 mg/L) S. pneumoniae isolates collected during the study were analysed for the presence of the mef(A) and erm(B) genes using primers described by Sutcliffe et al.5