ArticleThe Journal of infectious diseases2026
Ampicillin/Sulbactam in Combination with Ceftazidime/Avibactam Against Metallo-β-Lactamase-Producing Carbapenem-Resistant Acinetobacter baumannii: A Genomics-Informed Mechanism-based model.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed.
- Review
- Emergence of ceftazidime-avibactam resistance mediated by KPC variants KPC-71 and KPC-78 in ST463Microbiology spectrum · 2026Article
- Case Commentary: When one target is not enough-PBP3 insertions and target redundancy inAntimicrobial agents and chemotherapy · 2026Article
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.
Funding
Abstract
backgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) infections, driven by metallo- and class-D serine β-lactamases, pose significant therapeutic challenges. β-Lactam-based combinations offer a promising alternative to agents like colistin and tigecycline, which are associated with toxicity, and to cefiderocol, which is facing emerging resistance.
methodsThe pharmacodynamic activity of ampicillin/sulbactam and ceftazidime/avibactam was evaluated against three CRAB strains: AMA3, AMA133, and AMA205. Genotypic and phenotypic resistance profiles were characterized, and antibacterial activity was assessed using static concentration time-kill (SCTK) assays. A mechanism-based pharmacodynamic model (MBM) was developed using SCTK data, incorporating the bacterial resistome. This model informed the design of in vitro dynamic infection model studies, which were subsequently used to validate MBM predictions.
resultsThese strains harboring resistance genes including blaOXA-23 (AMA133), blaNDM-1 (AMA3), or both (AMA205) were resistant to ampicillin/sulbactam and ceftazidime/avibactam. However, combination therapy significantly reduced bacterial burden, achieving approximately 90% reduction in the area under the log10-CFU-versus-time curve for AMA133, and approximately 50-70% for AMA3 and AMA205.The MBM incorporated sulbactam hydrolysis by NDM-1 and OXA23 enzymes, along with drug acylation kinetics to penicillin-binding proteins. Potency (EC50) estimates revealed a resistance hierarchy: AMA3 > AMA205 > AMA133. Avibactam notably enhanced sulbactam's activity. Simulations and experimental validation demonstrated that high-dose ampicillin/sulbactam combinations were required to achieve 4-6 log10-CFU reductions in blaNDM-1 strains, while lower doses sufficed for AMA133.
conclusionsThis study highlights the potential of integrating genomic insights into MBM to optimize antibiotic regimens. The ampicillin/sulbactam and ceftazidime/avibactam combinations demonstrated promising activity against highly resistant CRAB strains, supporting their potential for clinical application in managing difficult-to-treat infections.
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.