ArticleAntimicrobial agents and chemotherapy2015
Role of the Outer Membrane and Porins in Susceptibility of β-Lactamase-Producing Enterobacteriaceae to Ceftazidime-Avibactam.
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 56 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- OmpK36 deficiency and inducible AmpC β-lactamase synergistically drive imipenem resistance inMicrobiology spectrum · 2026Article
- Deciphering the Genetic Mechanisms Driving Carbapenem Resistance: A Multicenter Study from Seven Egyptian Governorates Using Multiplex PCR and Whole Genome Sequencing.Current microbiology · 2026Article
- Article
- Evaluation of ceftazidime/avibactam in combination with colistin against KPC-2-producingJAC-antimicrobial resistance · 2025Article
- Use of MALDI-TOF VITEK MS for rapid and efficient identification of KPC-type carbapenemases in Enterobacterales carrying the Tn4401a transposon.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Impact of Hydrophobic, Hydrophilic, and Mucus-Binding Motifs on the Therapeutic Potential of Ceftazidime Analogs for Pulmonary Administration.Antibiotics (Basel, Switzerland) · 2025Article
- Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulentVirulence · 2024Article
- Impact of porin deficiency on the synergistic potential of colistin in combination with β-lactam/β-lactamase inhibitors against ESBL- and carbapenemase-producingAntimicrobial agents and chemotherapy · 2024Article
- Efflux pump-mediated resistance to new beta lactam antibiotics in multidrug-resistant gram-negative bacteria.Communications medicine · 2024Review
- Electrophysiological Insights into Antibiotic Translocation and Resistance: The Impact of Outer Membrane Proteins.Membranes · 2024Review
- Cephalosporin resistance, tolerance, and approaches to improve their activities.The Journal of antibiotics · 2024Review
- A Comprehensive Overview of the Antibiotics Approved in the Last Two Decades: Retrospects and Prospects.Molecules (Basel, Switzerland) · 2023Review
- Review
- Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam.WIREs mechanisms of disease · 2022Review
- A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones.Communications biology · 2022Article
- Cephalosporin translocation across enterobacterial OmpF and OmpC channels, a filter across the outer membrane.Communications biology · 2022Article
- Extensively Drug-Resistant Klebsiella pneumoniae Counteracts Fitness and Virulence Costs That Accompanied Ceftazidime-Avibactam Resistance Acquisition.Microbiology spectrum · 2022Article
- Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing.Antibiotics (Basel, Switzerland) · 2022Review
- Association ofAntibiotics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study examined the activity of the novel antimicrobial combination ceftazidime-avibactam against Enterobacteriaceae exhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates of Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine β-naphthylamide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes of E. coli and K. pneumoniae. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane of E. aerogenes, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazidime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species of Enterobacteriaceae studied were ≤ 8 mg/liter, regardless of outer membrane permeability changes resulting from an absence of defined porin proteins or upregulation of efflux.
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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.