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)
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".