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“Healthcare-associated ventriculitis and meningitis” is a potentially devastating illness following neurosurgical procedures. Multidrug resistant (MDR) and extensively drug resistant (XDR) organisms such as Acinetobacter baumannii and Klebsiella pneumoniae have increasingly been isolated in ventriculitis and meningitis episodes. The treatment of these infections can be challenging, as the antimicrobial options are restricted. Regarding Central Nervous System (CNS) infections the transfer of the antibiotics to the Cerebrospinal Fluid (CSF) is often low which results in decreased drug levels at the infection site. The intraventricular (IVT) administration of antibiotics can be used as an adjunct to the intravenous (IV) treatment of Gram-negative MDR ventriculitis and meningitis, yet pertinent data is scarce.We present the successful management of three cases of healthcare-associated ventriculitis and meningitis due to XDR species with the combined intraventricular administration of colistin and off-label tigecycline, after the initial regimen of colistin given alone through both IVT and IV routes had failed.