Pharmacodynamic activity of ertapenem versus penicillin-susceptible and penicillin-non-susceptible Streptococcus pneumoniae using an in vitro model
Bibliographic record
Abstract
BACKGROUND: Ertapenem is a novel carbapenem with activity against both penicillin-susceptible (MIC < or = 0.06 mg/L) and penicillin-non-susceptible (MIC > or = 0.12 mg/L) Streptococcus pneumoniae. This study assessed the pharmacodynamic activity of ertapenem against penicillin-susceptible and penicillin-non-susceptible S. pneumoniae using an in vitro pharmacodynamic model. METHODS: Fifteen S. pneumoniae strains including 3 penicillin-susceptible and 12 penicillin-non-susceptible [4 penicillin-intermediate (MIC 0.12-1 mg/L) and 8 penicillin-resistant (MIC > or = 2 mg/L); with different resistance phenotypes including erythromycin-resistant (MIC > or = 1 mg/L), ciprofloxacin-resistant (MIC > or = 4 mg/L) and doxycycline-resistant (MIC > or = 8 mg/L)] were studied. 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 f (free) 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 for 48 h to assess viable growth. RESULTS: Ertapenem T(> MIC) > or = 80% (ertapenem MICs < or = 0.5 mg/L) resulted in bactericidal (> or = 3 log10 killing) activity at 12, 24 and 48 h with complete eradication of penicillin-susceptible and penicillin-non-susceptible S. pneumoniae from the model with no regrowth over the 48 h study period. Ertapenem T(> MIC) < or = 63% (ertapenem MIC > or = 1 mg/L) resulted in bactericidal activity at 12 h with regrowth at 24 and 48 h. The observed MICs for S. pneumoniae of ertapenem studied in the in vitro model did not change during the 48 h period, even for strains where regrowth occurred. CONCLUSIONS: Ertapenem is bactericidal against both penicillin-susceptible and penicillin-non-susceptible S. pneumoniae (ertapenem MICs < or = 0.5 mg/L) when simulating free drug after 1 g intravenous once daily dosing.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".