<i>In vitro</i> activity of gepotidacin against urinary tract infection isolates of Enterobacterales, <i>Enterococcus faecalis</i> , and <i>Staphylococcus saprophyticus</i>
Bibliographic record
Abstract
ABSTRACT Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication through a distinct binding site and unique mechanism of action, providing well-balanced inhibition of two different type II topoisomerase enzymes for most uropathogens. Phase III clinical trials, NCT04020341 (EAGLE-2) and NCT04187144 (EAGLE-3), showed gepotidacin to be non-inferior and superior, respectively, to nitrofurantoin for the treatment of patients with uncomplicated urinary tract infections (uUTIs). To better define gepotidacin in vitro activity against pathogens that commonly cause UTIs, CLSI broth microdilution MICs were determined for gepotidacin and seven comparator agents, and agar dilution MICs were determined for fosfomycin, against 4,000 predominantly UTI isolates of Enterobacterales (3,250), Enterococcus faecalis (500), and Staphylococcus saprophyticus (250) collected globally from 2012 to 2020. Gepotidacin MIC 90 s against the Enterobacterales species tested were 4 µg/mL for Escherichia coli (1,000) and Klebsiella oxytoca (250), 8 µg/mL for Citrobacter spp. (250) and Klebsiella aerogenes (250), 16 µg/mL for Proteus mirabilis (250) and Providencia rettgeri (250), and 32 µg/mL for Enterobacter cloacae (500) and Klebsiella pneumoniae (500). Against the gram-positive species, gepotidacin MIC 90 s were 0.12 µg/mL and 4 µg/mL for S. saprophyticus (250) and E. faecalis (500), respectively. Gepotidacin MIC 90 s for ciprofloxacin not susceptible isolates ranged from 4 µg/mL for E. coli (352) to 128 µg/mL for P. rettgeri (48). Gepotidacin MIC 90 s for presumptive extended spectrum beta-laactamase (ESBL)-positive E. coli (228) and K. pneumoniae (145) were 8 µg/mL and 32 µg/mL, respectively. Gepotidacin was bactericidal (minimum bactericidal concentration [MBC]/MIC ratio ≤4) against 94% (47/50) of isolates tested.
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 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) | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".