Combination Therapy with Ceftazidime-Avibactam, Aztreonam, and Topical Polymyxin B for NDM-Producing Klebsiella pneumoniae CNS Infection: A Case Report

Background: Central nervous system (CNS)-associated infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) represent a major therapeutic challenge because of limited antibiotic penetration and severe clinical progression. Strains co-producing both Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) exhibit extensive drug resistance, including reduced susceptibility to ceftazidime–avibactam (CZA), leaving few effective treatment options. Reports of post-neurosurgical CNS infections caused by CZA-resistant, dual-carbapenemase–producing K. pneumoniae remain extremely uncommon. Case Presentation: A 61-year-old man developed a severe postoperative CNS infection following decompressive craniectomy for cerebellar infarction. The initial microbiology report from a previous hospital identified a KPC-positive, NDM-negative K. pneumoniae isolate, and treatment with intravenous CZA plus topical polymyxin B irrigation was initiated but proved ineffective. After transfer to our institution, repeat testing using a more sensitive molecular panel revealed that the pathogen actually co-harbored both KPC and NDM and was resistant to CZA, explaining the lack of initial clinical response. Based on these results, the antimicrobial regimen was modified to simultaneous intravenous ceftazidime–avibactam and aztreonam, together with topical polymyxin B irrigation via the surgical drainage catheter. The patient’s fever resolved within several days, cerebrospinal fluid parameters progressively normalized, and cultures became negative by treatment day 20. Subsequent complications required external ventricular drainage, neuroendoscopic septostomy, and eventual ventriculoperitoneal shunt placement. No nephrotoxicity or neurotoxicity occurred. At three-month follow-up, no recurrence of infection was observed, although neurological improvement was limited by the underlying brain injury. Conclusion: This case illustrates the diagnostic importance of repeat carbapenemase testing in refractory CNS infections and suggests that combined ceftazidime–avibactam plus aztreonam, with adjunctive topical polymyxin B, may be a useful therapeutic strategy for CZA-resistant, KPC- and NDM-co-producing K. pneumoniae CNS infections. Keywords: CNS infection, NDM-producing Klebsiella pneumoniae , KPC-producing Klebsiella pneumoniae , ceftazidime–avibactam, aztreonam, polymyxin B, carbapenem-resistant Enterobacterales