{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:22:21Z","timestamp":1770751341404,"version":"3.50.0"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shionogi GmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria (MRGN). At present, few data are available on the pharmacokinetics of this substance in critically ill patients, particularly for the treatment of central nervous system infections. Patients and Methods: Here, we reported on a 22-year-old male patient after severe open head trauma. Initial screening revealed colonization with 4MRGN A. baumannii (OXA-23) (perianal) and 4MRGN K. pneumoniae (KPC) (tracheal). Unfortunately, he developed ventriculitis (4MRGN A. baumannii). According to microbiological testing, the patient with normal renal function received 3 \u00d7 2 g\/d i.v. cefiderocol as a prolonged infusion (3 h) and colistin 3 \u00d7 3 Mio. IU\/d i.v. for 2 weeks. In addition to serum trough levels, drug monitoring was performed in the cerebrospinal fluid (CSF) via external ventricular drainage (24 h aliquots). Results: Serum and CSF specimens analyzed by liquid chromatography\u2013mass spectroscopy (LC-MS) in the presence of severe meningeal inflammation yielded average CSF concentrations of cefiderocol from 5.48 to 8.40 (median 6.98) \u03bcg\/mL and a concentration ratio CCSF mean\/Cserum trough from 0.38 to 0.76 (median 0.48). The cefiderocol levels in the CSF were sufficient for eradication of A. baumannii. A subsequent CSF infection with K. pneumoniae (found initially in screening and resistant to cefiderocol) after completed treatment with cefiderocol was successfully treated with gentamicin (intrathecally) and ceftazidime\/avibactam (i.v.). However, the patient died due to a Candida tropicalis infection detected in the CSF on day 71. Conclusions: Our results indicate that standard dosages of cefiderocol are sufficient for treatment of CNS infections in the presence of a severe disruption of the blood\u2013CSF barrier.<\/jats:p>","DOI":"10.3390\/antibiotics15020139","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:00:33Z","timestamp":1770022833000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cefiderocol for Treatment of Ventriculitis (4MRGN A. baumannii)\u2014Results of Therapeutic Drug Monitoring in Blood and Cerebrospinal Fluid"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5197-6328","authenticated-orcid":false,"given":"Melita","family":"Hadzifejzovic","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Emergency and Pain Medicine, Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Academic Teaching Hospital of the Johannes Gutenberg-University Mainz, D-56068 Koblenz, Germany"},{"name":"Department of Intensive Care Medicine, Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Academic Teaching Hospital of the Johannes Gutenberg-University Mainz, D-56068 Koblenz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Guevara Lara","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Emergency and Pain Medicine, Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Academic Teaching Hospital of the Johannes Gutenberg-University Mainz, D-56068 Koblenz, Germany"},{"name":"Department of Intensive Care Medicine, Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Academic Teaching Hospital of the Johannes Gutenberg-University Mainz, D-56068 Koblenz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-025X","authenticated-orcid":false,"given":"Samir G.","family":"Sakka","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Academic Teaching Hospital of the Johannes Gutenberg-University Mainz, D-56068 Koblenz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40265-019-1055-2","article-title":"Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant Gram-negative bacilli","volume":"79","author":"Zhanel","year":"2019","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"K\u00f6nig, C., Both, A., Rohde, H., Kluge, S., Frey, O.R., R\u00f6hr, A.C., and Wichmann, D. (2021). Cefiderocol in critically ill patients with multi-drug resistant pathogens: Real-life data on pharmacokinetics and microbiological surveillance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10060649"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107047","DOI":"10.1016\/j.ijantimicag.2023.107047","article-title":"Clinical efficacy of cefiderocol-based regimens in patients with carbapenem-resistant Acinetobacter baumannii infections: A systematic review with meta-analysis","volume":"63","author":"Gatti","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Karakonstantis, S., Rousaki, M., and Kritsotakis, E.I. (2022). Cefiderocol: Systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance. Antibiotics, 11.","DOI":"10.3390\/antibiotics11060723"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1186\/s13054-016-1523-y","article-title":"Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: A prospective observational study","volume":"20","author":"Blassmann","year":"2016","journal-title":"Crit. Care"},{"key":"ref_6","first-page":"1022","article-title":"A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis","volume":"28","author":"Grensemann","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","first-page":"80","article-title":"Can the transfer of vancomycin from the blood to the CSF space be estimated by CSF status parameters?","volume":"64","author":"Hardt","year":"2023","journal-title":"An\u00e4sth. Intensivmed."},{"key":"ref_8","first-page":"454","article-title":"Treatment with cefiderocol in K. pneumoniae KPC nosocomial external ventricular drainage meningitis: A brief report","volume":"30","author":"Colombo","year":"2022","journal-title":"Infez. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1093\/jac\/dkac248","article-title":"Plasma and cerebrospinal fluid concentrations of cefiderocol during successful treatment of carbapenem-resistant Acinetobacter baumannii meningitis","volume":"77","author":"Kufel","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"dlab188","DOI":"10.1093\/jacamr\/dlab188","article-title":"Real-life experience with compassionate use of cefiderocol for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections","volume":"3","author":"Meschiari","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/jac\/dkac066","article-title":"Cerebrospinal fluid concentrations of cefiderocol during the treatment of extensively drug-resistant Pseudomonas aeruginosa ventriculitis","volume":"77","author":"Bennis","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jgar.2022.11.019","article-title":"Intravenous cefiderocol for neurosurgical meningitis from an extensively drug-resistant New-Delhi metallo-\u03b2-lactamase-producing Pseudomonas aeruginosa strain","volume":"32","author":"Stevenson","year":"2023","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1128\/CMR.00007-10","article-title":"Penetration of drugs through the blood-cerebrospinal fluid\/blood-brain barrier for treatment of central nervous system infections","volume":"23","author":"Nau","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/ofid\/ofab466.1300","article-title":"Evaluation of penetration of cefiderocol into cerebrospinal fluid using a rat meningitis model","volume":"8","author":"Takemura","year":"2021","journal-title":"Open Forum Infect Dis."},{"key":"ref_15","first-page":"819","article-title":"Successful treatment of carbapenem-resistant Acinetobacter baumannii meningitis with sulbactam-durlobactam","volume":"79","author":"Tamma","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","first-page":"e49058","article-title":"Catheter-associated vancomycin-resistant Enterococcus faecium ventriculitis and multidrug-resistant Acinetobacter baumannii pneumonia with subsequent Acinetobacter ventriculitis: A case report","volume":"15","author":"Rei","year":"2023","journal-title":"Cureus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ofac391","DOI":"10.1093\/ofid\/ofac391","article-title":"Clinical cure of a difficult-to-treat resistant Pseudomonas aeruginosa ventriculitis using cefiderocol: A case report and literature review","volume":"9","author":"Marcelo","year":"2022","journal-title":"Open Forum Infect Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/phar.4632","article-title":"Pharmacokinetics of cefiderocol in a patient with carbapenem-resistant Acinetobacter baumannii ventriculitis: A case report","volume":"55","author":"Finch","year":"2025","journal-title":"Pharmacotherapy"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nau, R., Seele, J., and Eiffert, H. (2024). New antibiotics for the treatment of nosocomial central nervous system infections. Antibiotics, 13.","DOI":"10.3390\/antibiotics13010058"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/infdis\/149.4.568","article-title":"Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae","volume":"149","author":"Doroshow","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1093\/jac\/dkad277","article-title":"Plasmatic and CSF concentrations of cefiderocol in an infant with extensively drug-resistant Pseudomonas aeruginosa meningoencephalitis","volume":"78","author":"Funiciello","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13054-024-05214-5","article-title":"Therapeutic Drug Monitoring study group. High rates of cefidercol plasma target attainment: Results of a retrospective cohort study in 31 critically ill ICU patients","volume":"28","author":"Naumann","year":"2024","journal-title":"Crit. Care"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Loeuille, G., D\u2019huart, E., Vigneron, J., Nisse, Y.-E., Beiler, B., Polo, C., Ayari, G., Sacrez, M., Demor\u00e9, B., and Charmillon, A. (2022). Stability studies of 16 antibiotics for continuous infusion in intensive care units and for performing outpatient parenteral antimicrobial therapy. Antibiotics, 11.","DOI":"10.3390\/antibiotics11040458"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/2\/139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:51:25Z","timestamp":1770724285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/2\/139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["antibiotics15020139"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15020139","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]}}}