Pseudomonas aeruginosa meningitis following autologous hematopoietic stem cell transplantation

Pseudomonas aeruginosa meningitis following autologous hematopoietic stem cell transplantation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Pseudomonas aeruginosa meningitis following autologous hematopoietic stem cell transplantation Linas Davainis, Agata Bruzgul This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9178730/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background CNS infections caused by XDR Pseudomonas aeruginosa are life-threatening post-HSCT complications. The emergence of VIM-producing strains severely limits therapeutic options. Case presentation A 70-year-old male developed sepsis due to VIM-producing P. aeruginosa and subsequent meningitis on day + 7 post-autologous HSCT. Despite cefiderocol, meningitis was microbiologically confirmed. Therapy was optimized using 3-hour cefiderocol infusions plus intravenous and intrathecal colistin. The course was complicated by severe neurological decline and secondary thrombotic microangiopathy. Following intensive treatment, CSF sterilization was achieved. The patient ultimately recovered and was discharged with mild residual cognitive impairment. Conclusion This case highlights the efficacy of cefiderocol and dual-route colistin in treating XDR Gram-negative meningitis. Pseudomonas aeruginosa cefiderocol Gram-negative meningitis Figures Figure 1 Introduction Central nervous system (CNS) infections caused by Pseudomonas aeruginosa are rare but severe complications in immunocompromised patients. In the general adult population, P. aeruginosa meningitis is uncommon and occurs most frequently after neurosurgical procedures, whereas spontaneous cases are typically observed in patients with severe underlying diseases [ 1 – 3 ]. Among hematopoietic cell transplant recipients, invasive P. aeruginosa infections occur in approximately 1–2% of patients and are associated with high mortality rates, reaching 36% during the initial episode of infection [ 4 ]. Here, we present the case of a 70-year-old male who developed Pseudomonas aeruginosa sepsis and meningitis, which occurred following autologous hematopoietic stem cell transplantation. Case presentation A 70-year-old male with relapsed/refractory multiple myeloma underwent a second autologous hematopoietic stem cell transplantation (ASCT). Previously he was treated with multiple lines of therapy including VTD, VTD-PACE, daratumumab-based therapy, KRD, and the bispecific T-cell engager (BiTE) linvoseltamab. At the time of admission, the patient was in complete remission with ECOG performance status of 1. On day 6 post-ASCT, the patient sustained a scalp injury following an apparent fall and neuroimaging showed no acute traumatic pathology. By day 7, he developed febrile neutropenia (CRP 314.2 mg/L). Blood and central venous catheter cultures yielded VIM-producing Pseudomonas aeruginosa . Antimicrobial susceptibility testing (Table 1) demonstrated an extensively drug-resistant (XDR) phenotype, susceptible only to cefiderocol and colistin. Targeted therapy with cefiderocol (2g every 8 hours) IV was initiated. Antibiotic MIC [mg/L] Interpretation 1 Piperacillin/Tazobactam 32 R Cefepime >8 R Ceftazidime 16 R Imipenem >8 R Meropenem 4 I 2 Amikacin >16 R Ciprofloxacin >1 R Colistin 2 S Ceftazidime/Avibactam >8 R Aztreonam 8 R Cefiderocol 0.5 S Table 1. Antimicrobial susceptibility profile of the blood isolate of Pseudomonas aeruginosa . 1 Interpretations based on EUCAST clinical breakpoints. 2 (ATU): Susceptible, increased exposure (Area of Technical Uncertainty for P. aeruginosa ) Abbreviations: MIC, minimal inhibitory concentration; S, susceptible; R, resistant; I, intermediate. Despite neutrophil engraftment on day +11, the patient developed acute delirium. CSF analysis (Table 2) confirmed meningitis with persistent growth of VIM-producing P. aeruginosa , despite four days of cefiderocol. Parameter Day 11 Day 14 Day 16 Day 22 Day 32 White cell count in CSF (x10 6 /L) 60 654 1240 23 7 Polymorphonuclear neutrophil in CSF (%) 46 91 95 16 0 Lymphocytes in CSF (%) 43 7 3 68 81 CSF culture Pseudomonas aeruginosa Pseudomonas aeruginosa Pseudomonas aeruginosa Sterile Sterile Protein (g/L) 0.984 0.959 0.877 2.070 0.823 Glucose (mmol/L) 1,16 1,02 0,43 2,15 1364 Antimicrobial therapy Cefiderocol Cefiderocol + colistin Cefiderocol + colistin Cefiderocol Meropenem Table 2: CSF parameters and antibiotherapy received during hospitalization. Antimicrobial therapy was escalated to prolonged 3-hour cefiderocol infusions combined with intravenous and intrathecal (IT) colistin for 3 days (Table 3). Cultures from the scalp wound also yielded P. aeruginosa , suggesting a possible reservoir for persistent bacteremia. Day post-ASCT IT colistin IV colistin 14 0.25 MIU 8 MIU loading dose, followed by 5 MIU maintenance dose 15 - 10 MIU (5 MIU every 12 hours) 16 0.25 MIU 10 MIU (5 MIU every 12 hours) Table 3: Colistin infusion regimen. Abbreviations: IT, intrathecal; IV, intravenous; post-ASCT, post-autologous hematopoietic stem cell transplantation . Following the administration of IV and IT colistin, a transient decline in renal function was observed, with serum creatinine peaking at 243 μmol/L. Consequently, doses of concomitant drugs, including cefiderocol, were adjusted. Renal function recovered rapidly with hydration. Despite intensification of therapy, the patient’s neurological status deteriorated further. While CSF cultures remained positive, inflammatory parameters increased markedly (Table 2). On day 21, the patient progressed from delirium to stupor and eventually coma, with the Glasgow Coma Scale (GCS) score of 5. Examination showed fixed rightward gaze, horizontal nystagmus, meningismus, and myoclonic activity. Head CT remained unchanged. The patient was transferred to the intensive care unit (ICU). By day 22, CSF pleocytosis decreased and, for the first time, CSF cultures became sterile. Cefiderocol monotherapy was continued. Subsequent workup of thrombocytopenia revealed ADAMTS-13 activity of 0,29 IU/mL, raising suspicion of secondary thrombotic microangiopathy, and therapeutic plasma exchange was initiated. Following the combined antimicrobial and plasma exchange, the patient’s condition gradually improved. As the infection and thrombotic microangiopathy resolved, the patient’s neurological status steadily improved. On day 30, therapy was de-escalated to meropenem to complete the clinical course. He was eventually discharged home, microbiologically cured and hemodynamically stable, with only mild residual cognitive disorientation. The clinical course is summarized in Figure 1. Discussion CNS infections caused by XDR P. aeruginosa are rare but highly lethal in post-transplant patients, with limited evidence to guide therapy. In this case, the isolate was susceptible only to cefiderocol and colistin. Cefiderocol represents a potential therapeutic option for CNS infections caused by XDR Gram-negative pathogens. However, clinical data remain limited and largely restricted to small series and case reports. Available evidence suggests variable and often low CNS penetration, influenced by factors such as meningeal inflammation and critical illness, making pharmacokinetic optimization essential [5]. In our case, persistent CSF positivity despite early cefiderocol therapy suggests that standard dosing may be insufficient in CNS infections, likely due to pharmacokinetic constraints [6]. Escalation to prolonged 3-hour infusions was undertaken to optimize time above MIC, which may have contributed to subsequent microbiological clearance. These findings align with emerging data suggesting PK/PD optimization, rather than dose alone, is critical for efficacy in this setting [7]. The addition of intravenous and intrathecal colistin appeared decisive. Given the limited CNS penetration of systemic polymyxins, intrathecal administration likely enabled adequate bactericidal concentrations and facilitated CFS sterilization [8]. A key observation was the marked neurological deterioration occurring concurrently with microbiological response. The temporal association with neutrophil engraftment and pronounced CSF pleocytosis suggest that clinical worsening may have been driven by exaggerated inflammatory response following immune recovery rather than uncontrolled infection. This phenomenon resembles an immune reconstitution inflammatory syndrome (IRIS)-like process, which has been described in CNS infections and post-transplant settings, where paradoxical clinical deterioration occurs despite appropriate antimicrobial therapy [9]. Finally, the identification of colonized scalp wound underscores the importance of source control in preventing persistent bacteremia and CNS seeding. Conclusion This report contributes to the limited but growing clinical evidence supporting the potential role of cefiderocol in treating CNS infections caused by multidrug-resistant Gram-negative bacteria, particularly in situations where therapeutic options are extremely limited. Our findings also highlight the importance of treatment optimization and the potential role of inflammatory responses in clinical deterioration despite microbiological control. Declarations Funding None. Conflicts of Interest The authors declare no conflicts of interest. Informed Consent Written informed consent was obtained from the patient for publication of this case report. Author Contribution Both authors wrote and reviewed the manuscript Acknowledgments The authors would like to thank the microbiology laboratory staff and the nursing teams involved in the patient’s care. References Huang CR, Lu CH, Chuang YC, Tsai NW, Chang CC, Chen SF et al (2007) Adult Pseudomonas aeruginosa meningitis: high incidence of underlying medical and/or postneurosurgical conditions and high mortality rate. Jpn J Infect Dis 60(6):397–399 ‌Pai S, Bedford L, Ruramayi R, Aliyu SH, Sule J, Maslin D et al Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral hospital. QJM: An International Journal of Medicine. 2016 Feb 1;109(2):85–9 ‌Liu L, Zhu L, Hu C, Zhu S, Ye S (2024) Rare Cases of Pseudomonas aeruginosa Meningitis in Children: 10-Year Experience in a Single Center. J Child Neurol 39(3–4):113–121 ‌Hakki M, Limaye AP, Kim HW, Kirby KA, Corey L, Boeckh M (2007) Invasive Pseudomonas aeruginosa infections: high rate of recurrence and mortality after hematopoietic cell transplantation. Bone Marrow Transplantation. Apr 2;39(11):687–93 ‌Alessio Sollima, Rossini F, Lanza P, Pallotto C, Meschiari M, Gentile I et al (2024 May) Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art. Antibiotics 16(5):453–453 ‌Nau R, Seele J, Eiffert H (2024) New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections. Antibiotics. Jan 1;13(1):58 ‌Davide F, Bavaro, Belati A, Diella L, Stufano M, Romanelli F, Scalone L et al (2021) Cefiderocol-Based Combination Therapy for Difficult-to-Treat Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives. 29(6):652–652 ‌Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I et al (2009 Nov) Penetration of colistin into cerebrospinal fluid. Antimicrob Agents Chemother [Internet] 53(1):4907–4910 ‌Hu M, Liu S, Lu D, Zhong Y, Yu D, Qiu W et al (2021) Mar Case Report: Central Nervous System Immune Reconstitution Inflammatory Syndrome Related to Bacterial Meningitis. Frontiers in Immunology. 29;12.‌ Additional Declarations No competing interests reported. Supplementary Files 20260220135925.jpg Graphical abstract Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 27 Apr, 2026 Reviews received at journal 26 Apr, 2026 Reviewers agreed at journal 26 Apr, 2026 Reviewers invited by journal 07 Apr, 2026 Editor assigned by journal 22 Mar, 2026 Submission checks completed at journal 22 Mar, 2026 First submitted to journal 20 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9178730","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":611473678,"identity":"2c76917b-5abd-404b-a7f4-adede8fafeb1","order_by":0,"name":"Linas Davainis","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYBACPmYwBSIZGxgSGGyg4gW4tbChaUmDcgwMcGthgGsBg8NEaGHnPfjxB4O1vMHxw20PHvw5b88/u//gBwaDP3gcxpcszcOQbrjhTGK7QWLb7cQZdw4zS+C1hZnHQBroHsaZDYltEokNtxMYbiQzENJi/PMHw2H7mf0P2yQS/pyzl7+RzPyDgBYzCR6Gw4n9EkBbEtgOMG64kcxGyBYzax6D9OR+CaAtiW3JiRtvJJtZJBgY49TCz3/G+OaPCmvbNv70Z5I//tjZy91IfHzjQ4UcTi0QgOGKBAIaRsEoGAWjYBTgBwDZKEknEJ5DrQAAAABJRU5ErkJggg==","orcid":"","institution":"Vilnius University Hospital Santaros Klinikos","correspondingAuthor":true,"prefix":"","firstName":"Linas","middleName":"","lastName":"Davainis","suffix":""},{"id":611473679,"identity":"7cfdb1c3-f39f-4060-8996-764193f21b7e","order_by":1,"name":"Agata Bruzgul","email":"","orcid":"","institution":"Vilnius university","correspondingAuthor":false,"prefix":"","firstName":"Agata","middleName":"","lastName":"Bruzgul","suffix":""}],"badges":[],"createdAt":"2026-03-20 12:08:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9178730/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9178730/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105571331,"identity":"0ddb4d05-2e87-4f7f-9a9e-eb90086a0c39","added_by":"auto","created_at":"2026-03-27 13:22:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":138020,"visible":true,"origin":"","legend":"\u003cp\u003eClinical timeline of infection, microbiological findings, and treatment following autologous HSCT.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: ASCT, autologous stem cell transplantation; CSF, cerebrospinal fluid; GCS, Glasgow Coma Scale; IV, intravenous; IT, intrathecal; TMA, thrombotic microangiopathy; XDR, extensively drug-resistant.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure13.png","url":"https://assets-eu.researchsquare.com/files/rs-9178730/v1/83ee405ddfcf66320e06840b.png"},{"id":105574713,"identity":"c4968a0b-49be-43af-877f-e8ebb0b646a4","added_by":"auto","created_at":"2026-03-27 13:35:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":477820,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9178730/v1/c31a33b6-b1b3-4d4b-9848-9c936a217122.pdf"},{"id":105572503,"identity":"ecda518b-c699-4360-8b4a-c43daac1eb77","added_by":"auto","created_at":"2026-03-27 13:27:14","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1676269,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical abstract\u003c/p\u003e","description":"","filename":"20260220135925.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9178730/v1/0e4682021755bd58c135f0cb.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pseudomonas aeruginosa meningitis following autologous hematopoietic stem cell transplantation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCentral nervous system (CNS) infections caused by \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e are rare but severe complications in immunocompromised patients. In the general adult population, \u003cem\u003eP. aeruginosa\u003c/em\u003e meningitis is uncommon and occurs most frequently after neurosurgical procedures, whereas spontaneous cases are typically observed in patients with severe underlying diseases [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. Among hematopoietic cell transplant recipients, invasive \u003cem\u003eP. aeruginosa\u003c/em\u003e infections occur in approximately 1–2% of patients and are associated with high mortality rates, reaching 36% during the initial episode of infection [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we present the case of a 70-year-old male who developed \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e sepsis and meningitis, which occurred following autologous hematopoietic stem cell transplantation.\u003c/p\u003e "},{"header":"Case presentation","content":"\u003cp\u003eA 70-year-old male with relapsed/refractory multiple myeloma underwent a second autologous hematopoietic stem cell transplantation (ASCT). Previously he was treated with multiple lines of therapy including VTD, VTD-PACE, daratumumab-based therapy, KRD, and the bispecific T-cell engager (BiTE) linvoseltamab. At the time of admission, the patient was in complete remission with ECOG performance status of 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn day 6 post-ASCT, the patient sustained a scalp injury following an apparent fall and neuroimaging showed no acute traumatic pathology. By day 7, he developed febrile neutropenia (CRP 314.2 mg/L). Blood and central venous catheter cultures yielded VIM-producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. Antimicrobial susceptibility testing (Table 1) demonstrated an extensively drug-resistant (XDR) phenotype, susceptible only to cefiderocol and colistin. Targeted therapy with cefiderocol (2g every 8 hours) IV was initiated. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eMIC [mg/L]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eInterpretation\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003ePiperacillin/Tazobactam\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eCefepime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eCeftazidime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eImipenem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eMeropenem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eI\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eAmikacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eCiprofloxacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u0026gt;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eColistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eCeftazidime/Avibactam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eAztreonam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eCefiderocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Table 1. Antimicrobial susceptibility profile of the blood isolate of \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u0026nbsp;\u003c/sup\u003e\u003cem\u003eInterpretations based on EUCAST clinical breakpoints.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e (ATU): Susceptible, increased exposure (Area of Technical Uncertainty for \u003cem\u003eP. aeruginosa\u003c/em\u003e)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: MIC, minimal inhibitory concentration; S, susceptible; R, resistant; I, intermediate.\u0026nbsp;\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDespite neutrophil engraftment on day +11, the patient developed acute delirium. CSF analysis (Table 2) confirmed meningitis with persistent growth of VIM-producing \u003cem\u003eP. aeruginosa\u003c/em\u003e, despite four days of cefiderocol.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"705\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eDay 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eDay 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eDay 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eDay 22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eDay 32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eWhite cell count in CSF (x10\u003csup\u003e6\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003ePolymorphonuclear neutrophil in CSF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eLymphocytes in CSF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eCSF culture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eSterile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eSterile\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eProtein (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.984\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0.877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e2.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eGlucose (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e1,16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0,43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e2,15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eAntimicrobial therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eCefiderocol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eCefiderocol + colistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eCefiderocol + colistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eCefiderocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eMeropenem\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Table 2: CSF parameters and antibiotherapy received during hospitalization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAntimicrobial therapy was escalated to prolonged 3-hour cefiderocol infusions combined with intravenous and intrathecal (IT) colistin for 3 days (Table 3). Cultures from the scalp wound also yielded \u003cem\u003eP. aeruginosa\u003c/em\u003e, suggesting a possible reservoir for persistent bacteremia. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eDay post-ASCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eIT colistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eIV colistin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e14\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003e0.25 MIU\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e8 MIU loading dose, followed by 5 MIU maintenance dose\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e10 MIU (5 MIU every 12 hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003e0.25 MIU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e10 MIU (5 MIU every 12 hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Table 3: Colistin infusion regimen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: IT, intrathecal; IV, intravenous; post-ASCT, post-autologous hematopoietic stem cell transplantation\u003c/em\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing the administration of IV and IT colistin, a transient decline in renal function was observed, with serum creatinine peaking at 243 \u0026mu;mol/L. Consequently, doses of concomitant drugs, including cefiderocol, were adjusted. Renal function recovered rapidly with hydration. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite intensification of therapy, the patient\u0026rsquo;s neurological status deteriorated further. While CSF cultures remained positive, inflammatory parameters increased markedly (Table 2). On day 21, the patient progressed from delirium to stupor and eventually coma, with the Glasgow Coma Scale (GCS) score of 5. Examination showed fixed rightward gaze, horizontal nystagmus, meningismus, and myoclonic activity. Head CT remained unchanged. The patient was transferred to the intensive care unit (ICU).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBy day 22, CSF pleocytosis decreased and, for the first time, CSF cultures became sterile. Cefiderocol monotherapy was continued. Subsequent workup of thrombocytopenia revealed ADAMTS-13 activity of 0,29 IU/mL, raising suspicion of secondary thrombotic microangiopathy, and therapeutic plasma exchange was initiated. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Following the combined antimicrobial and plasma exchange, the patient\u0026rsquo;s condition gradually improved. As the infection and thrombotic microangiopathy resolved, the patient\u0026rsquo;s neurological status steadily improved. On day 30, therapy was de-escalated to meropenem to complete the clinical course. He was eventually discharged home, microbiologically cured and hemodynamically stable, with only mild residual cognitive disorientation. The clinical course is summarized in Figure 1.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCNS infections caused by XDR \u003cem\u003eP. aeruginosa\u0026nbsp;\u003c/em\u003eare rare but highly lethal in post-transplant patients, with limited evidence to guide therapy. In this case, the isolate was susceptible only to cefiderocol and colistin. Cefiderocol represents a potential therapeutic option for CNS infections caused by XDR Gram-negative pathogens. However, clinical data remain limited and largely restricted to small series and case reports. Available evidence suggests variable and often low CNS penetration, influenced by factors such as meningeal inflammation and critical illness, making pharmacokinetic optimization essential [5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our case, persistent CSF positivity despite early cefiderocol therapy suggests that standard dosing may be insufficient in CNS infections, likely due to pharmacokinetic constraints [6]. Escalation to prolonged 3-hour infusions was undertaken to optimize time above MIC, which may have contributed to subsequent microbiological clearance. These findings align with emerging data suggesting PK/PD optimization, rather than dose alone, is critical for efficacy in this setting [7].\u003c/p\u003e\n\u003cp\u003eThe addition of intravenous and intrathecal colistin appeared decisive. Given the limited CNS penetration of systemic polymyxins, intrathecal administration likely enabled adequate bactericidal concentrations and facilitated CFS sterilization [8].\u003c/p\u003e\n\u003cp\u003eA key observation was the marked neurological deterioration occurring concurrently with microbiological response. The temporal association with neutrophil engraftment and pronounced CSF pleocytosis suggest that clinical worsening may have been driven by exaggerated inflammatory response following immune recovery rather than uncontrolled infection. This phenomenon resembles an immune reconstitution inflammatory syndrome (IRIS)-like process, which has been described in CNS infections and post-transplant settings, where paradoxical clinical deterioration occurs despite appropriate antimicrobial therapy [9].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinally, the identification of colonized scalp wound underscores the importance of source control in preventing persistent bacteremia and CNS seeding.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis report contributes to the limited but growing clinical evidence supporting the potential role of cefiderocol in treating CNS infections caused by multidrug-resistant Gram-negative bacteria, particularly in situations where therapeutic options are extremely limited. Our findings also highlight the importance of treatment optimization and the potential role of inflammatory responses in clinical deterioration despite microbiological control.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e \u003ch2\u003eConflicts of Interest\u003c/h2\u003e \u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e \u003ch2\u003eInformed Consent\u003c/h2\u003e \u003cp\u003e Written informed consent was obtained from the patient for publication of this case report.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBoth authors wrote and reviewed the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors would like to thank the microbiology laboratory staff and the nursing teams involved in the patient\u0026rsquo;s care.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHuang CR, Lu CH, Chuang YC, Tsai NW, Chang CC, Chen SF et al (2007) Adult Pseudomonas aeruginosa meningitis: high incidence of underlying medical and/or postneurosurgical conditions and high mortality rate. Jpn J Infect Dis 60(6):397\u0026ndash;399\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Pai S, Bedford L, Ruramayi R, Aliyu SH, Sule J, Maslin D et al Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral hospital. QJM: An International Journal of Medicine. 2016 Feb 1;109(2):85\u0026ndash;9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Liu L, Zhu L, Hu C, Zhu S, Ye S (2024) Rare Cases of Pseudomonas aeruginosa Meningitis in Children: 10-Year Experience in a Single Center. J Child Neurol 39(3\u0026ndash;4):113\u0026ndash;121\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Hakki M, Limaye AP, Kim HW, Kirby KA, Corey L, Boeckh M (2007) Invasive Pseudomonas aeruginosa infections: high rate of recurrence and mortality after hematopoietic cell transplantation. Bone Marrow Transplantation. Apr 2;39(11):687\u0026ndash;93\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Alessio Sollima, Rossini F, Lanza P, Pallotto C, Meschiari M, Gentile I et al (2024 May) Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art. Antibiotics 16(5):453\u0026ndash;453\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Nau R, Seele J, Eiffert H (2024) New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections. Antibiotics. Jan 1;13(1):58\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Davide F, Bavaro, Belati A, Diella L, Stufano M, Romanelli F, Scalone L et al (2021) Cefiderocol-Based Combination Therapy for Difficult-to-Treat Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives. 29(6):652\u0026ndash;652\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I et al (2009 Nov) Penetration of colistin into cerebrospinal fluid. Antimicrob Agents Chemother [Internet] 53(1):4907\u0026ndash;4910\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026zwnj;Hu M, Liu S, Lu D, Zhong Y, Yu D, Qiu W et al (2021) Mar Case Report: Central Nervous System Immune Reconstitution Inflammatory Syndrome Related to Bacterial Meningitis. Frontiers in Immunology. 29;12.\u0026zwnj;\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pseudomonas aeruginosa, cefiderocol, Gram-negative meningitis","lastPublishedDoi":"10.21203/rs.3.rs-9178730/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9178730/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCNS infections caused by XDR \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e are life-threatening post-HSCT complications. The emergence of VIM-producing strains severely limits therapeutic options.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 70-year-old male developed sepsis due to VIM-producing \u003cem\u003eP. aeruginosa\u003c/em\u003e and subsequent meningitis on day + 7 post-autologous HSCT. Despite cefiderocol, meningitis was microbiologically confirmed. Therapy was optimized using 3-hour cefiderocol infusions plus intravenous and intrathecal colistin. The course was complicated by severe neurological decline and secondary thrombotic microangiopathy. Following intensive treatment, CSF sterilization was achieved. The patient ultimately recovered and was discharged with mild residual cognitive impairment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the efficacy of cefiderocol and dual-route colistin in treating XDR Gram-negative meningitis.\u003c/p\u003e","manuscriptTitle":"Pseudomonas aeruginosa meningitis following autologous hematopoietic stem cell transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-27 12:30:10","doi":"10.21203/rs.3.rs-9178730/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"262728443775245560696706309734974661493","date":"2026-04-27T07:35:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-26T15:10:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23035338801670207124517626143409286800","date":"2026-04-26T14:23:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T05:50:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-23T01:48:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-23T01:48:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","date":"2026-03-20T11:58:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9f382e33-2930-4ef4-aa8a-e48d1e1e006b","owner":[],"postedDate":"March 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T05:54:10+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-27 12:30:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9178730","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9178730","identity":"rs-9178730","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}