ArticleAntimicrobial agents and chemotherapy2015
Unexpected challenges in treating multidrug-resistant Gram-negative bacteria: resistance to ceftazidime-avibactam in archived isolates of Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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
87 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- Article
- Disarming carbapenemase-producingAntimicrobial agents and chemotherapy · 2026Article
- Current and future options for the treatment of serious infections due to carbapenem-resistantClinical microbiology reviews · 2025Review
- Molecular insights into the inhibition of MexCD-OprJ efflux pumps by menthol and thymol in Pseudomonas aeruginosa.Antonie van Leeuwenhoek · 2025Article
- Article
- Investigational antibiotic cefepime/zidebactam as a therapeutic option for the treatment of an unyielding empyema in a paediatric patient caused by extensively drug-resistant Pseudomonas aeruginosa: a case report.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms.Archives of microbiology · 2025Review
- Antibiotic Resistance and Virulence Determinants ofMicroorganisms · 2025Article
- Overcoming the drug resistance barrier: progress in fosfomycin combination therapy against multidrug-resistant pathogens.Frontiers in microbiology · 2025Review
- The Use of Ceftazidime-Avibactam in a Pediatric Intensive Care Unit-An Observational Prospective Study.Antibiotics (Basel, Switzerland) · 2024Article
- Antimicrobial Resistance ofMicroorganisms · 2024Article
- Efficacy and Safety of Ceftazidime-Avibactam Alone versus Ceftazidime-Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort.Antibiotics (Basel, Switzerland) · 2024Article
- Article
- Clinical distribution of carbapenem genotypes and resistance to ceftazidime-avibactam in Enterobacteriaceae bacteria.Frontiers in cellular and infection microbiology · 2024Article
- Article
- Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.Antibiotics (Basel, Switzerland) · 2023Review
- What to Do with the New Antibiotics?Antibiotics (Basel, Switzerland) · 2023Review
- Review
- Clinical efficacy and drug resistance of ceftazidime-avibactam in the treatment of Carbapenem-resistant gram-negative bacilli infection.Frontiers in microbiology · 2023Article
27 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
9 authors.
Funding
Abstract
Pseudomonas aeruginosa is a notoriously difficult-to-treat pathogen that is a common cause of severe nosocomial infections. Investigating a collection of β-lactam-resistant P. aeruginosa clinical isolates from a decade ago, we uncovered resistance to ceftazidime-avibactam, a novel β-lactam/β-lactamase inhibitor combination. The isolates were systematically analyzed through a variety of genetic, biochemical, genomic, and microbiological methods to understand how resistance manifests to a unique drug combination that is not yet clinically released. We discovered that avibactam was able to inactivate different AmpC β-lactamase enzymes and that blaPDC regulatory elements and penicillin-binding protein differences did not contribute in a major way to resistance. By using carefully selected combinations of antimicrobial agents, we deduced that the greatest barrier to ceftazidime-avibactam is membrane permeability and drug efflux. To overcome the constellation of resistance determinants, we show that a combination of antimicrobial agents (ceftazidime/avibactam/fosfomycin) targeting multiple cell wall synthetic pathways can restore susceptibility. In P. aeruginosa, efflux, as a general mechanism of resistance, may pose the greatest challenge to future antibiotic development. Our unexpected findings create concern that even the development of antimicrobial agents targeted for the treatment of multidrug-resistant bacteria may encounter clinically important resistance. Antibiotic therapy in the future must consider these factors.
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.