{"doi":"10.1128/msphere.00024-19","title":"OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs","abstract":"<jats:p>\n            The recent introduction of novel β-lactam/β-lactamase inhibitor combinations like ceftazidime-avibactam has increased our ability to treat infections caused by multidrug-resistant Gram-negative bacteria, including carbapenemase-producing\n            <jats:italic>Enterobacterales</jats:italic>\n            . However, the increasing number of cases of reported resistance to ceftazidime-avibactam is a concern. OXA-48 is a carbapenemase that has no significant effect on ceftazidime, but is inhibited by avibactam. Since isolates with OXA-48 frequently harbor extended-spectrum β-lactamases that are inhibited by avibactam, it is likely that ceftazidime-avibactam will be used to treat infections caused by OXA-48-producing\n            <jats:italic>Enterobacterales.</jats:italic>\n            Our data show that exposure to ceftazidime-avibactam can lead to changes in OXA-48, resulting in increased ability to hydrolyze ceftazidime and withstand the inhibitory effect of avibactam. Thus, resistance toward ceftazidime-avibactam among OXA-48-producing\n            <jats:italic>Enterobacterales</jats:italic>\n            should be monitored. Interestingly, the compromising effect of the amino acid substitutions in OXA-48 on other β-lactams and the effect of ceftazidime-avibactam exposure on the epidemic OXA-48 plasmid indicate that the evolution of ceftazidime-avibactam resistance comes with collateral effects.\n          </jats:p>","journal":"mSphere","year":2019,"id":663698,"datarank":0.6782682865573562,"base_score":4.5217885770490405,"endowment":4.5217885770490405,"self_citation_contribution":0.6782682865573562,"citation_network_contribution":0.0,"self_endowment_contribution":0.6782682865573562,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":91,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1732886,"name":"Vidar Sørum","orcid":null,"position":1,"is_corresponding":false},{"id":1732888,"name":"Ane Molden Thomassen","orcid":null,"position":2,"is_corresponding":false},{"id":1732890,"name":"Pål Jarle Johnsen","orcid":null,"position":3,"is_corresponding":false},{"id":1732891,"name":"Hanna-Kirsti S. Leiros","orcid":null,"position":4,"is_corresponding":false},{"id":1656640,"name":"Ørjan Samuelsen","orcid":"0000-0002-5525-2614","position":5,"is_corresponding":false},{"id":1732884,"name":"Christopher Fröhlich","orcid":"0000-0003-2682-2267","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs","abstract":"<jats:p>\n            The recent introduction of novel β-lactam/β-lactamase inhibitor combinations like ceftazidime-avibactam has increased our ability to treat infections caused by multidrug-resistant Gram-negative bacteria, including carbapenemase-producing\n            <jats:italic>Enterobacterales</jats:italic>\n            . However, the increasing number of cases of reported resistance to ceftazidime-avibactam is a concern. OXA-48 is a carbapenemase that has no significant effect on ceftazidime, but is inhibited by avibactam. Since isolates with OXA-48 frequently harbor extended-spectrum β-lactamases that are inhibited by avibactam, it is likely that ceftazidime-avibactam will be used to treat infections caused by OXA-48-producing\n            <jats:italic>Enterobacterales.</jats:italic>\n            Our data show that exposure to ceftazidime-avibactam can lead to changes in OXA-48, resulting in increased ability to hydrolyze ceftazidime and withstand the inhibitory effect of avibactam. Thus, resistance toward ceftazidime-avibactam among OXA-48-producing\n            <jats:italic>Enterobacterales</jats:italic>\n            should be monitored. Interestingly, the compromising effect of the amino acid substitutions in OXA-48 on other β-lactams and the effect of ceftazidime-avibactam exposure on the epidemic OXA-48 plasmid indicate that the evolution of ceftazidime-avibactam resistance comes with collateral effects.\n          </jats:p>","is_dataset_classified":null,"base_score":4.5217885770490405,"endowment":4.5217885770490405,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30918055","pmcid":"PMC6437269","openalex_id":"https://openalex.org/W2923095438","authors":[],"funders":[{"funder_name":"Helse Nord RHF","grant_id":"SFP1292-16","title":null},{"funder_name":"Joint Programming Initiative on Antimicrobial Resistance","grant_id":"271176/H10","title":null}],"total_grants":2,"fwci":3.5689,"citation_percentile":0.94921006,"influential_citations":0,"citation_trend":[{"year":2019,"count":2},{"year":2020,"count":12},{"year":2021,"count":19},{"year":2022,"count":19},{"year":2023,"count":13},{"year":2024,"count":11},{"year":2025,"count":9},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://msphere.asm.org/content/msph/4/2/e00024-19.full.pdf","host_type":"journal"},{"url":"https://msphere.asm.org/content/msph/4/2/e00024-19.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/mSphere.00024-19","host_type":"publisher"},{"url":"https://doi.org/10.1128/msphere.00024-19","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30918055","host_type":"repository"},{"url":"https://hdl.handle.net/10037/15099","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC6437269","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6437269","host_type":"repository"},{"url":"https://doaj.org/article/17e5f96f1a714a89b3f195058f277abd","host_type":"repository"},{"url":"https://doaj.org/article/a732550c267146dcbbc054c4c72bb839","host_type":"repository"},{"url":"https://www.helmholtz-berlin.de/pubbin/oai_publication?VT=1&ID=99598","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6437269","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6437269?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Antibiotic Resistance in Bacteria","Vibrio bacteria research studies","Antibiotics Pharmacokinetics and Efficacy"],"mesh_terms":["beta-Lactamases","Ceftazidime","Drug Combinations","Escherichia coli","Kinetics","Microbial Sensitivity Tests","Models, Molecular","Mutation","Crystallography, X-Ray","Evolution, Molecular","Amino Acid Substitution","Escherichia coli Proteins","Azabicyclo Compounds"],"keywords":["Ceftazidime/avibactam","Avibactam","Ceftazidime","Microbiology","Medicine","Biology","Chemistry","Bacteria","Pseudomonas aeruginosa","Genetics","Evolution","Klebsiella pneumoniae","Resistance development","Escherichia Coli","Carbapenem","Carbapenemase","Oxa-48","Collateral Sensitivity","Ceftazidime-avibactam"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"refseq"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T23:09:34.072493Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}