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Intracranial infections caused by multidrug-resistant Gram-negative bacterium have led to considerable mortality due to extremely limited treatment options. Herein, we firstly reported a clinical carbapenem-resistant  Escherichia coli  isolate coharboring  bla   NDM   –  5  and  bla   CTX   –   M   –  65  from a patient with post-craniotomy meningitis. The carbapenem-resistant  Escherichia coli  strain CNEC001 belonging to Sequence Type 410 was only susceptible to amikacin and tigecycline, both of which have poor penetration through the blood-brain barrier (BBB). The  bla   CTX   –   M   –  65  gene was expressed on a 135,794 bp IncY plasmid. The  bla   NDM   –  5  gene was located on a genomic island region of an IncX3-type plasmid pNDM5-CNEC001. Based on the characteristics of the strain, we presented the successful treatment protocol of intravenous (IV) tigecycline and amikacin combined with intrathecal (ITH) amikacin in this study. Intracranial infection caused by  Escherichia coli  coharboring  bla   NDM   –  5  and  bla   CTX   –   M   –  65  is rare and fatal. Continuous surveillance and infection control measures for such strain need critical attention in clinical settings.

Successful Treatment of Severe Post-craniotomy Meningitis Caused by an Escherichia coli Sequence Type 410 Strain Coharboring blaNDM–5 and blaCTX–M–65