Pharmacodynamic activity of ertapenem versus multidrug-resistant genotypically characterized extended-spectrum -lactamase-producing Escherichia coli using an in vitro model
Bibliographic record
Abstract
BACKGROUND: This study assessed the pharmacodynamic activity of ertapenem against multidrug-resistant (MDR) genotypically characterized extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli using an in vitro model. METHODS: Six ESBL-producing E. coli with the CTX-M-15 genotype were studied. All six strains were MDR (defined as resistance to third-generation cephalosporins and > or = two other unrelated antimicrobial classes). The in vitro pharmacodynamic model was inoculated with 1 x 10(6) cfu/mL, and ertapenem was dosed once daily at 0 and 24 h to simulate free (f) Cmax and t(1/2) obtained after a standard 1 g intravenous once-daily dose in healthy volunteers (fCmax, 15 mg/L; t(1/2), 4 h). Sampling was performed over 48 h to assess viable growth and resistance selection. RESULTS: Ertapenem T(>MIC) > or = 98% (ertapenem MICs < or = 0.25 mg/L) resulted in bactericidal (> or = 3 log(10) killing) activity at 6, 12, 24 and 48 h against all strains. Eradication of organisms from the in vitro model (below the level of detection) occurred at 2 h followed by slow regrowth of the majority of the strains (5 of 6) over 12, 24 and 48 h time points. Despite limited regrowth, ertapenem achieved a bactericidal effect against all strains (all time points) over the 48 h study period. CONCLUSIONS: Ertapenem was rapidly bactericidal (in approximately 2 h) against MDR ESBL (CTX-M-15)-producing E. coli (ertapenem MICs < or = 0.25 mg/L) when simulating free drug after 1 g intravenous once-daily dosing. This bactericidal activity was maintained over the 48 h experimental period with only minor regrowth, which was not associated with MIC increase from baseline.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".