{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:33:25Z","timestamp":1792794805760,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"11","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI100560"],"award-info":[{"award-number":["R01AI100560"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI063517"],"award-info":[{"award-number":["R01AI063517"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI072219"],"award-info":[{"award-number":["R01AI072219"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cleveland Department of Veterans Affairs","award":["1I01BX001974"],"award-info":[{"award-number":["1I01BX001974"]}]},{"name":"Biomedical Laboratory Research & Development Service of the VA Office of Research and Development","id":[{"id":"https:\/\/ror.org\/011qyt180","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Geriatric Research Education and Clinical Center VISN 10","id":[{"id":"https:\/\/ror.org\/01nh3sx96","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)\u2013producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Therapeutic drug monitoring (TDM) was performed in 3 patients with health care\u2013associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5\u2005g infused intravenously every 8\u2005hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography\/mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25\/4, 4\/4, and 0.25\/4 \u03bcg\/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0\u2005\u00b5g\/mL (CAZ component) and 4.20 to 0.92\u2005\u00b5g\/mL (AVI component), respectively. AVI achieved concentrations \u22651\u2005\u00b5g\/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT &amp;gt; MIC, which are associated with efficient bacterial killing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofad507","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T19:28:28Z","timestamp":1697570908000},"source":"Crossref","is-referenced-by-count":17,"title":["Utilizing Ceftazidime\/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant\n                    <i>Pseudomonas aeruginosa<\/i>\n                    and KPC-Producing Enterobacterales"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-1769","authenticated-orcid":false,"given":"Mohamad","family":"Yasmin","sequence":"first","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center , Cleveland, Ohio , USA {C}%3C!%2D%2D%7BC%7D%253C!%252D%252D%257BC%257D%25253C!%25252D%25252D%25257C%25257CrmComment%25257C%25257C%25253C~show%252520%25255BAQ%252520ID%25253DAQ12%25255D~%25253E%25252D%25252D%25253E%252D%252D%253E%2D%2D%3E"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-2618","authenticated-orcid":false,"given":"Amir","family":"Nutman","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Marshall","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center , Cleveland, Ohio , USA {C}%3C!%2D%2D%7BC%7D%253C!%252D%252D%257BC%257D%25253C!%25252D%25252D%25257C%25257CrmComment%25257C%25257C%25253C~show%252520%25255BAQ%252520ID%25253DAQ12%25255D~%25253E%25252D%25252D%25253E%252D%252D%253E%2D%2D%3E"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-9791","authenticated-orcid":false,"given":"Dafna","family":"Yahav","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liad","family":"Lupinsky","sequence":"additional","affiliation":[{"name":"Neurosurgical Department, Rabin Medical Center, Beilinson Campus , Petah Tiqva , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M","family":"Hujer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adarsh","family":"Bhimraj","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Houston Methodist Hospital , Houston, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4784-3227","authenticated-orcid":false,"given":"David","family":"van Duin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina , Chapel Hill, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center , Cleveland, Ohio , USA {C}%3C!%2D%2D%7BC%7D%253C!%252D%252D%257BC%257D%25253C!%25252D%25252D%25257C%25257CrmComment%25257C%25257C%25253C~show%252520%25255BAQ%252520ID%25253DAQ12%25255D~%25253E%25252D%25252D%25253E%252D%252D%253E%2D%2D%3E"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"},{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"},{"name":"CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES) , Cleveland, Ohio , USA"},{"name":"Departments of Proteomics and Bioinformatics, Pharmacology, and Biochemistry, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"2023113021494681000_ofad507-B1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/QCO.0000000000000418","article-title":"Pharmacokinetics and pharmacodynamics of antibiotics in central nervous system infections","volume":"31","author":"Nau","year":"2018","journal-title":"Curr Opin Infect Dis"},{"key":"2023113021494681000_ofad507-B2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s40262-013-0062-9","article-title":"Clinical pharmacokinetics of antibacterials in cerebrospinal fluid","volume":"52","author":"Di 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