ArticleAntimicrobial agents and chemotherapy2019
Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam-β-Lactamase Inhibitor Combination.
Article in Antimicrobial agents and chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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
62 citing papers in PubMed, 111 citations in OpenAlex.
- Trial
- Cefepime 2.0: Upgrading β-Lactamase Inhibitor Use.Microorganisms · 2026Review
- Reply to Feng, "Recalculation of inhibitor concentration fold-changes for CMY-219: comments on a recent article about CMY-219 conferring resistance to ceftazidime-avibactam".Antimicrobial agents and chemotherapy · 2026Article
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- Challenges and opportunities in the management of severe pneumonia. Key concepts from the Seventh Annual Meeting of Spanish Experts 2025.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026Review
- Zwitterionic Penicillin-Derived Sulfone Inhibitor for Combating β-Lactamase-Mediated Antibiotic Resistance.ChemMedChem · 2026Article
- Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.Antibiotics (Basel, Switzerland) · 2026Review
- Article
- Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Antibacterial activity of enmetazobactam againstAntimicrobial agents and chemotherapy · 2026Article
- CEFEPIME/ENMETAZOBACTAM: Physicochemical Stability of a Novel β-Lactam/β-Lactamase Inhibitor Combination in Syringes and Elastomeric Devices.Antibiotics (Basel, Switzerland) · 2026Article
- In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates.The Journal of antimicrobial chemotherapy · 2026Article
- Cefepime/enmetazobactam for Gram-negative periprosthetic joint infections? A randomized porcine study on target tissue pharmacokinetics.The Journal of antimicrobial chemotherapy · 2026Article
- A Review ofInternational journal of microbiology · 2026Review
- Mechanistic basis for inhibition of the extended-spectrum β-lactamase GES-1 by enmetazobactam and tazobactam.FEBS letters · 2025Article
- Genetic diversity, biochemical properties, epidemiology, and detection methods of IMP- and VIM-type carbapenemases.Clinical microbiology reviews · 2025Review
- Structure and mechanism of taniborbactam inhibition of the cefepime-hydrolyzing, partial R2-loop deletionAntimicrobial agents and chemotherapy · 2025Article
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- CombattingAntibiotics (Basel, Switzerland) · 2025Review
- Towards a holistic approach to pulmonary infections. Insights from the Sixth Annual Meeting of Spanish Experts 2024.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2025Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Impeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum β-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone β-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of β-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the
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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.