{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:17:30Z","timestamp":1789183050316,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, and the Berlin Institute of Health at Charit\u00e9 (BIH)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: A novel fixed combination of aztreonam (ATM) and avibactam (AVI) offers promising potential to treat infections with carbapenem-resistant Enterobacterales (CRE) producing metallo-\u03b2-lactamases (MBL). This study aimed to assess the accuracy of population pharmacokinetic (PK) models for ATM-AVI in predicting in vivo concentrations in a critically ill patient with CRE infection during its first clinical use. Methods: A 70-year-old male with septic shock due to hospital-acquired pneumonia (HAP) caused by MBL-producing Klebsiella pneumoniae was treated with ATM-AVI. Trough and peak serum concentrations (32 samples over 7 days) were measured using liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS). Population PK models were used to simulate complete concentration\u2013time profiles. Bland\u2013Altman analysis assessed model performance by comparing predicted and measured concentrations. Results: Median ATM trough concentrations (18.4 mg\/L) remained above the minimum inhibitory concentration (MIC) of 1 mg\/L for the pathogen. The Bland\u2013Altman analysis demonstrated reasonable agreement between predicted and observed concentrations, with a relative bias (rBias) of \u221250.5% for ATM and \u221214.4% for AVI. ATM-AVI ratios remained stable. Clinical improvement and sterile blood cultures within 12 days led to intensive care unit (ICU) discharge. Conclusions: Population PK models for ATM-AVI accurately predicted in vivo concentrations in a severely ill patient with HAP. Therapeutic drug monitoring (TDM) with PK modeling ensured optimal antimicrobial exposure and contributed to clinical recovery.<\/jats:p>","DOI":"10.3390\/jpm14121135","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["First Clinical Application of Aztreonam\u2013Avibactam in Treating Carbapenem-Resistant Enterobacterales: Insights from Therapeutic Drug Monitoring and Pharmacokinetic Simulations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-9275","authenticated-orcid":false,"given":"Oliver","family":"H\u00f6lsken","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, BIH Academy, Junior Clinician Scientist Program, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Corporate Member of Freie Universit\u00e4t Berlin and HumboldtUniversit\u00e4t zu Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"},{"name":"German Rheumatology Research Center (DRFZ), a Leibnitz Institute, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keno","family":"Sponheuer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4654-7434","authenticated-orcid":false,"given":"Franz","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany"},{"name":"Graduate Research Training Program PharMetrX, Freie Universit\u00e4t Berlin\/Universit\u00e4t Potsdam, 12169 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Martens-Lobenhoffer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Otto-Von-Guericke University of Magdeburg, University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie M.","family":"Bode-B\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Otto-Von-Guericke University of Magdeburg, University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9344-8514","authenticated-orcid":false,"given":"Charlotte","family":"Kloft","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany"},{"name":"Graduate Research Training Program PharMetrX, Freie Universit\u00e4t Berlin\/Universit\u00e4t Potsdam, 12169 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-7680","authenticated-orcid":false,"given":"Sascha","family":"Treskatsch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-6968","authenticated-orcid":false,"given":"Stefan","family":"Angermair","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","unstructured":"Pfennigwerth, N., Cremanns, M., Eisfeld, J., Hans, J., Anders, A., and Gatermann, S.G. 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