Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum -lactamases, AmpC -lactamases and reduced susceptibility to carbapenems using an in vitro model
Bibliographic record
Abstract
BACKGROUND: Escherichia coli harbouring extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and reduced susceptibility to carbapenems (CRS) are increasing worldwide. This study assessed the in vitro pharmacodynamic activity of tigecycline against E. coli with ESBLs, AmpCs and CRS. METHODS: Nine E. coli isolates were studied, including three ESBL-producing isolates, three AmpC-producing isolates and three isolates demonstrating CRS (ertapenem MIC > or = 0.12 mg/L). The pharmacodynamic model was inoculated with organisms at 1 x 10(6) cfu/mL and tigecycline dosed once every 24 h to simulate the fC(max) (free peak serum concentration) and t(1/2) (serum half-life) obtained after standard dosing of 100 mg intravenously every 24 h (fC(max), 0.15 mg/L; t(1/2), 42 h). Samples were collected over 48 h. RESULTS: For isolates with a tigecycline fAUC(24)/MIC of 2.0 (tigecycline MIC = 0.5 mg/L), tigecycline demonstrated bacteriostatic activity with < 1 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC(24)/MIC was 4.0 (tigecycline MIC = 0.25 mg/L), tigecycline demonstrated bacteriostatic activity with approximately 1.5 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC(24)/MIC was 8.0 (tigecycline MIC = 0.12 mg/L), tigecycline demonstrated bacteriostatic activity with approximately 2.0 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. CONCLUSIONS: Tigecycline demonstrated approximately 1-2 log(10) killing against E. coli harbouring ESBLs, AmpC beta-lactamases and CRS when simulating clinically achievable serum concentrations, and represents a potential therapy for infections caused by these isolates.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 | 0.001 |
| 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".