Azithromycin resistance is co-evolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae
Bibliographic record
Abstract
Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-gener-ation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZMr)Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommenda-tions, and analyzed the clonal distribution of AZMr isolates in Ontario, Canada. Nineteen AZMr clinical isolates (one per patient; MIC,>2g/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, charac-terization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZMr level; group A isolates displayed high-level resistance (MIC,>2,048g/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates hadmoderate resistance to AZM (MICs, 2 to 8g/ml, C2599Tmutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25g/ml, PBP2 pattern XXXIV). This AZMr phenotype was not ob-served in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZMMICs of 0.25 to 0.5g/ml associated withmtrRmutations). We hypothesized that the AZMmutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than theMPC in wild-type isolates (AZMMIC,<0.031g/ml), increasing the chances of additional selection of AZMr mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 teacher head, 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".