Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study
Abstract Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with cefta...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2021-02, Vol.76 (3), p.775-783 |
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| creator | Karaiskos, I Daikos, G L Gkoufa, A Adamis, G Stefos, A Symbardi, S Chrysos, G Filiou, E Basoulis, D Mouloudi, E Galani, L Akinosoglou, K Arvaniti, K Masgala, A Petraki, M Papadimitriou, E Galani, I Poulakou, G Routsi, C Giamarellou, H |
| description | Abstract
Background
Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required.
Objectives
To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs).
Methods
A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity.
Results
One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival.
Conclusions
Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp. |
| doi_str_mv | 10.1093/jac/dkaa503 |
| format | Article |
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Background
Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required.
Objectives
To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs).
Methods
A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity.
Results
One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival.
Conclusions
Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkaa503</identifier><identifier>PMID: 33249436</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Anti-Bacterial Agents - therapeutic use ; Azabicyclo Compounds - therapeutic use ; Bacterial Proteins ; beta-Lactamases ; Ceftazidime - therapeutic use ; Drug Combinations ; Humans ; Klebsiella Infections - drug therapy ; Klebsiella Infections - mortality ; Klebsiella pneumoniae ; Microbial Sensitivity Tests ; Registries</subject><ispartof>Journal of antimicrobial chemotherapy, 2021-02, Vol.76 (3), p.775-783</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c320t-83f973e40cddac266c45429d2565ac5412b3707f78f4b081aa3e1fae27fdcb573</citedby><cites>FETCH-LOGICAL-c320t-83f973e40cddac266c45429d2565ac5412b3707f78f4b081aa3e1fae27fdcb573</cites><orcidid>0000-0002-2226-0239 ; 0000-0001-6455-9848</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33249436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karaiskos, I</creatorcontrib><creatorcontrib>Daikos, G L</creatorcontrib><creatorcontrib>Gkoufa, A</creatorcontrib><creatorcontrib>Adamis, G</creatorcontrib><creatorcontrib>Stefos, A</creatorcontrib><creatorcontrib>Symbardi, S</creatorcontrib><creatorcontrib>Chrysos, G</creatorcontrib><creatorcontrib>Filiou, E</creatorcontrib><creatorcontrib>Basoulis, D</creatorcontrib><creatorcontrib>Mouloudi, E</creatorcontrib><creatorcontrib>Galani, L</creatorcontrib><creatorcontrib>Akinosoglou, K</creatorcontrib><creatorcontrib>Arvaniti, K</creatorcontrib><creatorcontrib>Masgala, A</creatorcontrib><creatorcontrib>Petraki, M</creatorcontrib><creatorcontrib>Papadimitriou, E</creatorcontrib><creatorcontrib>Galani, I</creatorcontrib><creatorcontrib>Poulakou, G</creatorcontrib><creatorcontrib>Routsi, C</creatorcontrib><creatorcontrib>Giamarellou, H</creatorcontrib><creatorcontrib>Hellenic Ceftazidime/Avibactam Registry Study Group</creatorcontrib><creatorcontrib>the Hellenic Ceftazidime/Avibactam Registry Study Group</creatorcontrib><title>Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Background
Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required.
Objectives
To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs).
Methods
A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity.
Results
One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival.
Conclusions
Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.</description><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Azabicyclo Compounds - therapeutic use</subject><subject>Bacterial Proteins</subject><subject>beta-Lactamases</subject><subject>Ceftazidime - therapeutic use</subject><subject>Drug Combinations</subject><subject>Humans</subject><subject>Klebsiella Infections - drug therapy</subject><subject>Klebsiella Infections - mortality</subject><subject>Klebsiella pneumoniae</subject><subject>Microbial Sensitivity Tests</subject><subject>Registries</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAURoMoOj5W7iUrEaROmkc7dSeDLxxwo-tym9xotE1r0ooj_ngrM7p09W0Oh49DyGHKzlJWiOkL6Kl5BVBMbJBJKjOWcFakm2TCBFNJLpXYIbsxvjDGMpXNtsmOEFwWUmQT8jVH28OnM67BKby7CnQPDXWe9s9IMQBtLdUQKujQYwMRky60ZtDOP9G7GqvosK6Bdh6HpvUO8JziR4fBoddIbWgbCtRD71oPNQ345GIfljT2g1nuky0LdcSD9e6Rx6vLh_lNsri_vp1fLBItOOuTmbBFLlAybQxonmVaKskLw1WmQCuZ8krkLLf5zMqKzVIAgakF5Lk1ulK52CMnK-94_W3A2JeNi_rnt8d2iCWXmcqVKlQxoqcrVIc2xoC27IJrICzLlJU_ucsxd7nOPdJHa_FQNWj-2N--I3C8Atqh-9f0DSnPi6Y</recordid><startdate>20210211</startdate><enddate>20210211</enddate><creator>Karaiskos, I</creator><creator>Daikos, G L</creator><creator>Gkoufa, A</creator><creator>Adamis, G</creator><creator>Stefos, A</creator><creator>Symbardi, S</creator><creator>Chrysos, G</creator><creator>Filiou, E</creator><creator>Basoulis, D</creator><creator>Mouloudi, E</creator><creator>Galani, L</creator><creator>Akinosoglou, K</creator><creator>Arvaniti, K</creator><creator>Masgala, A</creator><creator>Petraki, M</creator><creator>Papadimitriou, E</creator><creator>Galani, I</creator><creator>Poulakou, G</creator><creator>Routsi, C</creator><creator>Giamarellou, H</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2226-0239</orcidid><orcidid>https://orcid.org/0000-0001-6455-9848</orcidid></search><sort><creationdate>20210211</creationdate><title>Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study</title><author>Karaiskos, I ; Daikos, G L ; Gkoufa, A ; Adamis, G ; Stefos, A ; Symbardi, S ; Chrysos, G ; Filiou, E ; Basoulis, D ; Mouloudi, E ; Galani, L ; Akinosoglou, K ; Arvaniti, K ; Masgala, A ; Petraki, M ; Papadimitriou, E ; Galani, I ; Poulakou, G ; Routsi, C ; Giamarellou, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c320t-83f973e40cddac266c45429d2565ac5412b3707f78f4b081aa3e1fae27fdcb573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Azabicyclo Compounds - therapeutic use</topic><topic>Bacterial Proteins</topic><topic>beta-Lactamases</topic><topic>Ceftazidime - therapeutic use</topic><topic>Drug Combinations</topic><topic>Humans</topic><topic>Klebsiella Infections - drug therapy</topic><topic>Klebsiella Infections - mortality</topic><topic>Klebsiella pneumoniae</topic><topic>Microbial Sensitivity Tests</topic><topic>Registries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karaiskos, I</creatorcontrib><creatorcontrib>Daikos, G L</creatorcontrib><creatorcontrib>Gkoufa, A</creatorcontrib><creatorcontrib>Adamis, G</creatorcontrib><creatorcontrib>Stefos, A</creatorcontrib><creatorcontrib>Symbardi, S</creatorcontrib><creatorcontrib>Chrysos, G</creatorcontrib><creatorcontrib>Filiou, E</creatorcontrib><creatorcontrib>Basoulis, D</creatorcontrib><creatorcontrib>Mouloudi, E</creatorcontrib><creatorcontrib>Galani, L</creatorcontrib><creatorcontrib>Akinosoglou, K</creatorcontrib><creatorcontrib>Arvaniti, K</creatorcontrib><creatorcontrib>Masgala, A</creatorcontrib><creatorcontrib>Petraki, M</creatorcontrib><creatorcontrib>Papadimitriou, E</creatorcontrib><creatorcontrib>Galani, I</creatorcontrib><creatorcontrib>Poulakou, G</creatorcontrib><creatorcontrib>Routsi, C</creatorcontrib><creatorcontrib>Giamarellou, H</creatorcontrib><creatorcontrib>Hellenic Ceftazidime/Avibactam Registry Study Group</creatorcontrib><creatorcontrib>the Hellenic Ceftazidime/Avibactam Registry Study Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karaiskos, I</au><au>Daikos, G L</au><au>Gkoufa, A</au><au>Adamis, G</au><au>Stefos, A</au><au>Symbardi, S</au><au>Chrysos, G</au><au>Filiou, E</au><au>Basoulis, D</au><au>Mouloudi, E</au><au>Galani, L</au><au>Akinosoglou, K</au><au>Arvaniti, K</au><au>Masgala, A</au><au>Petraki, M</au><au>Papadimitriou, E</au><au>Galani, I</au><au>Poulakou, G</au><au>Routsi, C</au><au>Giamarellou, H</au><aucorp>Hellenic Ceftazidime/Avibactam Registry Study Group</aucorp><aucorp>the Hellenic Ceftazidime/Avibactam Registry Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2021-02-11</date><risdate>2021</risdate><volume>76</volume><issue>3</issue><spage>775</spage><epage>783</epage><pages>775-783</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Background
Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required.
Objectives
To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs).
Methods
A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity.
Results
One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival.
Conclusions
Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33249436</pmid><doi>10.1093/jac/dkaa503</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-2226-0239</orcidid><orcidid>https://orcid.org/0000-0001-6455-9848</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0305-7453 |
| ispartof | Journal of antimicrobial chemotherapy, 2021-02, Vol.76 (3), p.775-783 |
| issn | 0305-7453 1460-2091 |
| language | eng |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Anti-Bacterial Agents - therapeutic use Azabicyclo Compounds - therapeutic use Bacterial Proteins beta-Lactamases Ceftazidime - therapeutic use Drug Combinations Humans Klebsiella Infections - drug therapy Klebsiella Infections - mortality Klebsiella pneumoniae Microbial Sensitivity Tests Registries |
| title | Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study |
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