ArticleThe Journal of infectious diseases2019
Ceftazidime-Avibactam in Combination With Fosfomycin: A Novel Therapeutic Strategy Against Multidrug-Resistant Pseudomonas aeruginosa.
Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Is less always more? Ceftazidime/avibactam alone or in combination to treat infections caused by Pseudomonas aeruginosa: a retrospective observational multi-centre cohort study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Observational
- Screening and molecular characterization of plasmid-mediated fosfomycin resistance in Enterobacterales.Molecular biology reports · 2026Article
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Biotherapeutic strategies for quorum quenching in Salmonella Typhi: a review.Archives of microbiology · 2026Review
- Temporin-GHa-derived peptides enhance the antibacterial and antibiofilm activities of polymyxin B against Pseudomonas aeruginosa and Escherichia coli.Archives of microbiology · 2026Article
- Article
- Treatment of central nervous system infections caused byFrontiers in medicine · 2026Review
- Current and future options for the treatment of serious infections due to carbapenem-resistantClinical microbiology reviews · 2025Review
- Management of Carbapenem Resistant Gram-Negative Infections.Indian journal of pediatrics · 2025Review
- Difficult-to-TreatAntibiotics (Basel, Switzerland) · 2025Review
- Carbapenem treatment options for metallo-beta-lactamase: drug screening and dose optimization of meropenem-based combinations against NDM- or IMP-producingFrontiers in microbiology · 2025Article
- Overcoming the drug resistance barrier: progress in fosfomycin combination therapy against multidrug-resistant pathogens.Frontiers in microbiology · 2025Review
- 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
- Meropenem-Vaborbactam for the Treatment of Post-Neurosurgical Meningitis Caused by KPC Producer Klebsiella Pneumoniae: A Case Report and Review of the Literature.Antibiotics (Basel, Switzerland) · 2024Article
- Pharmacokinetic/pharmacodynamic analysis of ceftazidime/avibactam and fosfomycin combinations in anMicrobiology spectrum · 2024Article
- Intravenous Fosfomycin for Systemic Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2023Review
- Ceftazidime-Avibactam as Osteomyelitis Therapy: A Miniseries and Review of the Literature.Antibiotics (Basel, Switzerland) · 2023Article
- Antimicrobial Resistance inMicroorganisms · 2023Article
- The place of new antibiotics for Gram-negative bacterial infections in intensive care: report of a consensus conference.Annals of intensive care · 2023Review
- Reliability of E-Tests and the Phoenix Automated Method in Assessing Susceptibility to IV Fosfomycin-Comparative Studies Relative to the Reference Method.Pathogens (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
Previously, by targeting penicillin-binding protein 3, Pseudomonas-derived cephalosporinase (PDC), and MurA with ceftazidime-avibactam-fosfomycin, antimicrobial susceptibility was restored among multidrug-resistant (MDR) Pseudomonas aeruginosa. Herein, ceftazidime-avibactam-fosfomycin combination therapy against MDR P. aeruginosa clinical isolate CL232 was further evaluated. Checkerboard susceptibility analysis revealed synergy between ceftazidime-avibactam and fosfomycin. Accordingly, the resistance elements present and expressed in P. aeruginosa were analyzed using whole-genome sequencing and transcriptome profiling. Mutations in genes that are known to contribute to β-lactam resistance were identified. Moreover, expression of blaPDC, the mexAB-oprM efflux pump, and murA were upregulated. When fosfomycin was administered alone, the frequency of mutations conferring resistance was high; however, coadministration of fosfomycin with ceftazidime-avibactam yielded a lower frequency of resistance mutations. In a murine infection model using a high bacterial burden, ceftazidime-avibactam-fosfomycin significantly reduced the P. aeruginosa colony-forming units (CFUs), by approximately 2 and 5 logs, compared with stasis and in the vehicle-treated control, respectively. Administration of ceftazidime-avibactam and fosfomycin separately significantly increased CFUs, by approximately 3 logs and 1 log, respectively, compared with the number at stasis, and only reduced CFUs by approximately 1 log and 2 logs, respectively, compared with the number in the vehicle-treated control. Thus, the combination of ceftazidime-avibactam-fosfomycin was superior to either drug alone. By employing a "mechanism-based approach" to combination chemotherapy, we show that ceftazidime-avibactam-fosfomycin has the potential to offer infected patients with high bacterial burdens a therapeutic hope against infection with MDR P. aeruginosa that lack metallo-β-lactamases.
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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.