ReviewAntimicrobial agents and chemotherapy2022
Leaks in the Pipeline: a Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020.
Review in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed.
- Article
- Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical Pipeline.Antibiotics (Basel, Switzerland) · 2026Review
- The 3D Value Framework for Sustainable Access to Effective Antibiotics.Health care analysis : HCA : journal of health philosophy and policy · 2026Article
- Random Forest Modeling to Predict Small Molecule Accumulation in Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- New inhibitors of themSphere · 2026Article
- From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Antibiotic hybrids: A promising strategy to replenish the pipeline and combat antimicrobial resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Negamycin: Nature's Forgotten Antibiotic.ACS infectious diseases · 2026Review
- Article
- Siderophore cephalosporins.EcoSal Plus · 2025Review
- A Comprehensive Overview of Antimicrobial Peptides: Broad-Spectrum Activity, Computational Approaches, and Applications.Antibiotics (Basel, Switzerland) · 2025Review
- Inhibiting Lipopolysaccharide Biogenesis: The More You Know the Further You Go.Annual review of biochemistry · 2025Review
- Nanobody-Targeted Conditional Antimicrobial Therapeutics.ACS nano · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Review
- Depth-Resolved Temperature-Dependent Penetration of Polymyxin B in Phospholipids/Lipopolysaccharide Asymmetric Bilayers.ACS omega · 2025Article
- Nanoceria Anti-inflammatory and Antimicrobial Nanodrug: Cellular and Molecular Mechanism of Action.Current medicinal chemistry · 2025Article
- Antimicrobial resistance at a turning point: microbial drivers, one health, and global futures.Frontiers in microbiology · 2025Review
- Development of polymyxin- and aminoglycoside-based outer membrane permeabilizers: a review.Frontiers in microbiology · 2025Review
- Recent advances in small molecule LpxC inhibitors against gram-negative bacteria (2014-2024).Frontiers in microbiology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
The World Health Organization (WHO) has warned that our current arsenal of antibiotics is not innovative enough to face impending infectious diseases, especially those caused by multidrug-resistant Gram-negative pathogens. Although the current preclinical pipeline is well stocked with novel candidates, the last U.S. Food and Drug Administration (FDA)-approved antibiotic with a novel mechanism of action against Gram-negative bacteria was discovered nearly 60 years ago. Of all the antibiotic candidates that initiated investigational new drug (IND) applications in the 2000s, 17% earned FDA approval within 12 years, while an overwhelming 62% were discontinued in that time frame. These "leaks" in the clinical pipeline, where compounds with clinical potential are abandoned during clinical development, indicate that scientific innovations are not reaching the clinic and providing benefits to patients. This is true for not only novel candidates but also candidates from existing antibiotic classes with clinically validated targets. By identifying the sources of the leaks in the clinical pipeline, future developmental efforts can be directed toward strategies that are more likely to flow into clinical use. In this review, we conduct a detailed failure analysis of clinical candidates with Gram-negative activity that have fallen out of the clinical pipeline over the past decade. Although limited by incomplete data disclosure from companies engaging in antibiotic development, we attempt to distill the developmental challenges faced by each discontinued candidate. It is our hope that this insight can help de-risk antibiotic development and bring new, effective antibiotics to the clinic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.