Antimicrobial Activity of Solithromycin against Clinical Isolates of
Bibliographic record
Abstract
The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth mi-crodilutionmethod. Solithromycin had aMIC50 of<0.015g/ml and aMIC90 of 0.031g/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 andMIC90, 0.125g/ml and 1g/ml, respectively). Ninety-nine percent of the iso-lates hadMICs for solithromycin ranging from<0.015g/ml to 0.031g/ml, whereas 83.6 % of the isolates showedMICs for AZM ranging from 0.062g/ml to 0.25g/ml. Interestingly, 96.7 % (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5g/ml to 2g/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of soli-thromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within hu-man lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1 or 8MICs, dis-playing bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis. Legionellosis is a major public health concern in industrializedcountries. Manifestations of the disease range from a mild
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".