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Paper text:
intrathecal ( it ) antibiotics have been increasingly utilized for neurosurgical patients with ventriculitis and meningitis .
the indication for such use of antibiotics often occurs in the setting of inability to sterilize cerebrospinal fluid ( csf ) despite treatment with systemic therapy .
the efficacy and safety of such antibiotic administration have been well described over the years , especially in the cases of vancomycin and gentamicin.1 however , the use and safety profile of newer generation antibiotics via an it route remains relatively uncertain .
here , we present a case of a 32-year - old female patient with enterococcus faecalis ventriculitis who was successfully treated with it linezolid in addition to systemic antibiotic therapy .
in august 2014 , a 31-year - old female patient was originally diagnosed with glioblastoma and subsequently underwent surgical resection via a left frontal craniotomy .
the initial antibiotic regimen included vancomycin for which the patient developed a severe allergic reaction . during this time period ,
the patient underwent multiple wound washouts and revisions though she repeatedly presented back to the hospital with fever and drainage from her cranial incision . eventually , after developing hydrocephalus , the patient had an external ventricular drain ( evd ) placed in april 2015 .
shortly thereafter , she was started on therapy with intravenous aztreonam for csf cultures growing klebsiella pneumoniae .
repeat cultures additionally grew candida albicans for which intravenous voriconazole was added to the antimicrobial regimen . despite this , the patient continued to have surgical site drainage and intermittent fevers .
weeks later , further repeat cultures grew extended spectrum -lactamase producing klebsiella and nonvancomycin - resistant e. faecalis as aztreonam was switched to imipenem for appropriate coverage based on sensitivity profiles of the above microbes . again , despite the above therapy , the patient continued to experience marked confusion with fevers and purulent drainage from the surgical site .
in addition , the hospital was experiencing a shortage in imipenem for which the patient was transitioned to meropenem .
of note , oral linezolid 600  mg twice daily was also added to the regimen to provide further coverage for the e. faecalis considering the lower efficacy of meropenem ( vs. imipenem ) and the patient 's history of severe allergic reaction to vancomycin and cephalosporins . over the next week , the patient had minimal clinical change as csf cultures drawn every 48 hours failed to show clearance of the e. faecalis , despite ventricular catheter exchange .
considering the persistence of infection , the decision to add it linezolid was made given that sensitivities demonstrated antibiotic resistance to gentamycin .
it linezolid was thus started and administered via the evd at 10  mg daily at a concentration of 2 mg / ml . after 6 days of adding it linezolid , the patient showed sterilization of her csf . from a clinical perspective ,
10 days into her course of it linezolid , the patient began to regain some physical and mental function , prompting removal of the evd and ventriculoperitoneal shunt placement . at this time , the it linezolid was discontinued ( after receiving 15 days of total it therapy ) though the systemic antibiotics remained .
postoperatively , the patient continued to show stability and improvement , and she was discharged to a rehabilitation facility without complication .
the patient remained stable and was doing well until 3 months later when she returned to the hospital with worsening confusion and recurrent tonic  clonic seizures .
workup at that time revealed intracranial hemorrhage associated with significant recurrent tumor burden and midline shift . considering the degree of the patient 's symptoms and overall poor prognosis , the patient was made comfort care at that time and discharged home under the guidance of hospice .
it antibiotics have increasingly been shown to be an effective and safe method of drug delivery in neurosurgical cases , especially in those involving antibiotics that do not achieve good central nervous system penetration and in cases wherein csf sterilization proves to be difficult .
our case here presents the use of it linezolid , which has not been previously well described .
linezolid is often considered as a therapeutic option in cases of methicillin - resistant staphylococcus aureus and vancomycin - resistant e. faecalis ( vre ) , where other antibiotics may not be tolerated based on side - effect profiles .
situations of vre meningitis have previously been described in multiple case reports and include treatment via both systemic options ( primarily with linezolid or daptomycin ) and it options ( quinupristin - dalfopristin , chloramphenicol , daptomycin).2 
 3 
 4 despite this , there is a paucity of data regarding the use of it linezolid .
earlier reports of central nervous system ( cns ) penetrance of linezolid are widely variable , ranging from 28 to 70%.5 
 6 a better understanding of the drug 's action in the cns following systemic administration is necessary to elucidate benefits of administering the drug it .
as presented in our case , a patient with multiple antibiotic allergies and an evd - related e. faecalis csf infection that does not clear with prolonged use of systemic linezolid ( 8 days ) , demonstrating antibiotic resistance to gentamycin , and despite ventricular catheter exchange ( excluding the possibility of bacterial colonization ) , may serve as a good candidate for the use of it linezolid . here
, the use of it linezolid did show rapid clearance of e. faecalis and sterilization of the csf within 6 days of initiation . from a clinical perspective , there were no immediately apparent adverse reactions to the it linezolid , as the patient was believed to have cleared her infection .
however , considering the patient 's intracranial bleed associated with tumor progression / recurrence and death 3 months later ; it is difficult to fully evaluate the true impact and efficacy of this treatment . despite this difficult outcome , we hope this case presents an example of the use of it linezolid and how it may be dosed and serve as a mechanism for csf sterilization in difficult neurosurgical infections in the future .
background  the use of intrathecal antibiotic therapy for the treatment of ventriculitis and/or meningitis has demonstrated efficacy especially when sterilization of the cerebrospinal fluid is not possible with intravenous antibiotics alone . 
 
 case description  we describe the successful treatment of enterococcus faecalis ventriculitis utilizing intrathecal linezolid in a 32-year - old female patient with severe allergy to vancomycin , prohibitive bacterial susceptibilities , and failure of previous attempts to sterilize the cerebrospinal fluid despite multimodal treatment . 
 
 conclusion  intrathecal linezolid is a useful treatment in the setting of multidrug - resistant bacterial ventriculitis . 
 we present a useful dosing regimen for the administration of intrathecal linezolid .