Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin
Bibliographic record
Abstract
Plazomicin (formerly ACHN-490) is a next-generation aminoglycoside that was synthetically derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'. Plazomicin inhibits bacterial protein synthesis and exhibits dose-dependent bactericidal activity. Plazomicin demonstrates activity against both Gram-negative and Gram-positive bacterial pathogens, including isolates harboring any of the clinically relevant aminoglycoside-modifying enzymes. However, like older parenteral aminoglycosides, plazomicin is not active against bacterial isolates expressing ribosomal methyltransferases conferring aminoglycoside resistance. Plazomicin has been reported to demonstrate in vitro synergistic activity when combined with daptomycin or ceftobiprole versus methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus and against Pseudomonas aeruginosa when combined with cefepime, doripenem, imipenem or piperacillin-tazobactam. After intravenous administration of plazomicin to humans at a dose of 15 mg/ kg, the maximum concentraration was 113 μg/ml, the area under the curve(0-24) was 239 h·μg/ml, the half-life was 4.0 h and the steady-state volume of distribution was 0.24 L/kg. Results from a Phase II randomized, double-blind study in patients with complicated urinary tract infection and acute pyelonephritis including cases with concurrent bacteremia comparing plazomicin 15 mg/kg intravenously once daily for 5 days with levofloxacin 750 mg intravenously. for 5 days are anticipated in 2012. Human studies to date have not reported nephrotoxicity or ototoxicity, and lack of ototoxicity has been reported in the guinea pig model. Given reported increases in bacterial resistance to current antimicrobial agents and the lack of availability of new agents with novel mechanisms, plazomicin may become a welcomed addition to the antibacterial armamentarium pending positive results from large-scale clinical trials and other required clinical studies.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.001 | 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".