Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
Bibliographic record
Abstract
OBJECTIVES: To support the clinical development of mecillinam and pivmecillinam in the United States for the treatment of complicated and uncomplicated urinary tract infections (UTIs), this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTIs in the United States during 2017 to 2020. Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam and is recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated UTIs and is approved for the treatment of uncomplicated UTIs in Europe, Canada, and the United States. METHODS: A total of 3303 isolates were collected and antimicrobial susceptibility determined according to Clinical Laboratory and Standards Institute (CLSI) guidelines. RESULTS: Susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against extended-spectrum beta-lactamase (ESBL)-positive bacteria susceptibilities were highest for mecillinam (98.2% susceptible) and fosfomycin (97.3% susceptible) and against ESBL-positive K. pneumoniae only mecillinam and fosfomycin had > 80% susceptibility. Resistance to comparator antibiotics was highest for trimethoprim-sulfamethoxazole (27.1%), followed by ciprofloxacin (19.3%), ceftriaxone (19.2%), and nitrofurantoin (12.1%). Multi-drug-resistant isolates were most susceptible to mecillinam and fosfomycin. CONCLUSION: The data further support the clinical development and clinical utility of mecillinam. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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".