Cerebrospinal fluid white cell count to red cell count ratio as a predictor of ventriculitis in patients with external ventricular drains.

INTRODUCTION: External ventricular drain (EVD) associated ventriculitis is a complication of EVD placement associated with significant morbidity and mortality. Gold-standard for EVD associated bacterial ventriculitis diagnosis involves cerebrospinal fluid (CSF) sampling from the EVD with microscopy, culture and sensitivity testing. The ratio of white blood cells to red blood cells has anecdotally been considered a predictive factor in diagnosing EVD associated ventriculitis, however no study has been done demonstrating this. METHODS: A retrospective cross-sectional study was designed to assess whether the ratio of CSF white blood cells to red blood cells could be used to diagnose EVD associated ventriculitis. Data was collected for all patients undergoing EVD insertion at a major neurosurgical unit in Sydney, Australia. A receiver operator characteristics (ROC) curve was used to determine if this ratio was useful, and Youden's index was calculated to determine the appropriate cut-off point. RESULTS: This sample of n = 157 consecutive patients a total of 29 patients were diagnosed with ventriculitis. The area under the ROC curve was significant (0.706, P <0.001), and Youden's index demonstrated an appropriate cut-off point was a ratio of 1:106. DISCUSSION: CSF parameters have long been considered predictive of EVD associated ventriculitis. We demonstrated that using a component of routine testing it is possible to accurately predict a ventriculitis diagnosis. As the ratio is used, it enables discrimination in a raised white blood cell count due to local trauma with interventricular bleeding. CONCLUSION: CSF white blood cell to red blood cell ratio is an appropriate diagnostic test for ventriculitis.

Factors and measures predicting external CSF drain-associated ventriculitis: A review and meta-analysis.

OBJECTIVE: To determine the diagnostic value of clinical factors and biochemical or microbiological measures for diagnosing a drain-associated ventriculitis, we summarized the available evidence. METHODS: We performed a systematic review and meta-analysis of studies of patients with external ventricular CSF drains who developed drain-associated ventriculitis by searching MEDLINE, EMBASE, and CENTRAL electronic database. We reported the occurrence of abnormal test results in patients with and without drain-associated ventriculitis. For continuous variables, we recalculated mean values presented in multiple studies. RESULTS: We identified 42 articles published between 1984 and 2018 including 3,035 patients with external CSF drains of whom 697 (23%) developed drain-associated bacterial ventriculitis. Indications for drain placement were subarachnoid, intraventricular or cerebral hemorrhage or hemorrhage not further specified (69%), traumatic brain injury (13%), and obstructive hydrocephalus secondary to a brain tumor (10%). Fever was present in 116 of 162 patients with ventriculitis (72%) compared with 80 of 275 (29%) patients without ventriculitis. The CSF cell count was increased for 74 of 80 patients (93%) with bacterial ventriculitis and 30 of 95 patients (32%) without ventriculitis. CSF culture was positive in 125 of 156 episodes classified as ventriculitis (80%), and CSF Gram stain was positive in 44 of 81 patients (54%). In patients with ventriculitis, PCR on ribosomal RNA was positive on 54 of 78 CSF samples (69%). CONCLUSION: Clinical factors and biochemical and microbiological measures have limited diagnostic value in differentiating between ventriculitis and sterile inflammation in patients with external CSF drains. Prospective well-designed diagnostic accuracy studies in drain-associated ventriculitis are needed.

Tumor necrosis factor alpha and interleukin-1 beta levels in cerebrospinal fluid examination for the diagnosis of ventriculoperitoneal shunt-related ventriculitis.

PURPOSE: Ventriculitis is known to develop after chronic inflammation and bacterial invasion of the ventricular surface with a recurrence of shunt infections. The aim of this study is to evaluate the diagnostic value of elevation in cerebrospinal fluid (CSF) interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) together with CSF culture and laboratory test results in the diagnosis of ventriculoperitoneal (VP) shunt-related ventriculitis, which is known to be more problematic than conventional shunt infection. METHODS: The study included a total of 34 patients with a VP shunt due to hydrocephalus, who presented with a headache, fever, and shunt infection at the Emergency Department and had a pre-diagnosis of ventriculitis. Nineteen patients were diagnosed with shunt-related infection or ventriculitis using the CSF obtained from the shunt pump. The IL-1ß and TNF-α levels from the CSF samples of all patients were measured using the Micro ELISA immunoassay method. RESULTS: CSF direct microscopic observation revealed that the mean cell count, IL-1ß level, CRP level, and blood leukocyte level were higher in patients with ventriculitis compared to those diagnosed with shunt infection (p = 0.02, p = 0.009, p = 0.004, and p = 0.009, respectively). The probability of predicting positive culture outcome was 92.7% with 90.9% sensitivity and 82.6% specificity when IL-1ß values exceeded 4.0 pg/ml. TNF-α values did not show a significant, reliable pattern compared to IL-1ß. CONCLUSIONS: IL-1ß is a reliable parameter which shall be used in the diagnosis of ventriculitis by predicting positive culture outcome with high sensitivity and specificity.

Interleukin 6 in the Cerebrospinal Fluid as a Biomarker for Onset of Vasospasm and Ventriculitis After Severe Subarachnoid Hemorrhage.

OBJECTIVE: The aim of the study was to investigate the diagnostic potential of interleukin 6 (IL-6) and other soluble biomarkers in serum and cerebrospinal fluid (CSF) for early diagnosis of cerebral vasospasm (cVSSAH) and external ventricular drain-associated ventriculitis (VCSAH) and to separate these conditions from aneurysmal subarachnoid hemorrhage (aSAH) without further complication (SAHw/o/c). METHODS: The concentrations of serum biomarkers and markers in the CSF were collected in 63 consecutive patients with aSAH and external ventricular drainage. Arithmetical means and standard deviations, area under the curve (AUC), cutoff values (C-OFF), sensitivity (SE), and specificity (SP) were calculated for markers and their correlation with SAHw/o/c, cVSSAH, and VCSAH. RESULTS: Clinical courses included 27 patients with cVSSAH, 17 with VCSAH, and 19 with SAHw/o/c. Mean ± standard deviationCSFIL-6 values were 7588 ± 4580 pg/mL at onset of VCSAH and 4102 ± 4970 pg/mL for cVSSAH and higher than 234 ± 239 pg/mL in SAHw/o/c (P < 0.001). CSFIL-6 showed excellent diagnostic potential for differing between VCSAH and SAHw/o/c (AUC, 1.00; C-OFF, 707; SE, 100%; SP, 100%), and a moderate diagnostic potential for differing VCSAH from cVSSAH (AUC, 0.757; C-OFF, 3100 pg/Ml; SE, 86.7%; SP, 70.6%). The concentration of CSFIL-6 within the cVSSAH group was significantly increased compared with SAHw/o/c (AUC, 0.937; C-OFF, 530 pg/mL; SE, 87.5%; SP, 91.7%). CONCLUSIONS: CSFIL-6 is increased after aSAH in patients with cVSSAH or VCSAH. Patients with a CSFIL-6 level higher than a C-OFF of 3100 pg/mL have an increased likelihood for VCSAH; patients with CSFIL-6 levels between 530 and 3100 pg/mL have an increased posttest probability for cVSSAH.

Management of Pyogenic Cerebral Ventriculitis by Neuroendoscopic Surgery.

BACKGROUND: Pyogenic cerebral ventriculitis is a debilitating form of intracranial infection with an unfavorable outcome as a result of lack of experience in surgical management. OBJECTIVE: To study retrospectively a group of pyogenic cerebral ventriculitis patients managed by neuroendoscopic surgery (NES). METHODS: The standard intraventricular protocols of NES to treat this disease included 1 or more of the following: 1) obliteration of debris, 2) evidence of microbial infection, 3) septomy, 4) incision of the septation, or 5) monitoring catheter insertion. Modified external ventricular drainage EVD (mEVD) was combined with NES when intraventricular debris and bacterial plaques could not be evacuated completely. Subsequent surgical treatment strategies depended on the clinical manifestation, cerebrospinal fluid analysis, and mEVD blockage tests approximately 3 weeks after the last NES. RESULTS: Forty-one patients, who were distributed in 7 hospitals and underwent NES, were included. Five patients received 1 NES, 18 received 2, 16 received 3, and 2 received 4. mEVD was performed in all patients, and mean mEVD duration in the hospital was 27.6 days. At discharge, 15 patients were cured, 15 were cured but ventriculoperitoneal shunt dependent, 9 were mEVD dependent, and 2 died (mean modified Rankin Scale score was 2.48). Two mEVD-dependent patients died, and no other outcomes changed during postoperative follow-up (mean modified Rankin Scale score, 2.67). CONCLUSIONS: The results suggest a relatively favorable outcome for management of pyogenic cerebral ventriculitis by NES. The techniques and strategies are practical and should be applied more extensively.

Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study.

BACKGROUND: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. METHODS: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics. RESULTS: In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60.7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability. CONCLUSIONS: Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis.

Meningitis related ventriculitis--experience from a tertiary care centre in northern India.

OBJECTIVE: To assess clinical profile and short term outcome of patients with meningitis related ventriculitis. METHODS: Case records of 47 patients admitted with a diagnosis of ventriculitis (complicating meningitis) over 3 y were analysed retrospectively. RESULTS: The mean age of patients was 4.96 mo (20 d - 42 mo). The common symptoms were fever (27/47), enlarging head (23/47) and seizures (12/47) with signs of raised intracranial pressure (29/47). Ventricular cerebro-spinal fluid (CSF) showed mean cells - 237 cells/µL, sugar - 36 mg/dL and protein - 568 mg/dL. Gram stain and/or culture were positive in 5 patients. Ultrasonography of the head (done in 32 of 47 patients) showed hydrocephalus in 29 and internal echoes, debris or septations in ventricles in 5 patients. Computed tomography (CT) of brain (done in 42 of 47 patients) showed hydrocephalus in 36, abscesses in 7, ependymal enhancement in 4, infarcts in 4 and subdural empyema in 3 patients. MRI brain (done in 13 patients) showed hydrocephalus in all, 6 had cysts and 3 had ependymal enhancement. Thirty seven patients were started on ceftriaxone combined with vancomycin/cloxacillin with/without amikacin, and 10 patients received vancomycin and meropenem. Mean duration of antibiotics treatment was 4.17 wk (range; 0.8-12 wk). External ventricular drainage (EVD) was done in 22/47 patients. Cure rate (improvement in clinical and CSF parameters) in patients with external ventricular drainage was 59% as against 50% in patients who received antibiotics alone. At least 19 patients required ventriculoperitoneal (VP) shunt for unresolved significant hydrocephalus by discharge. There were 10 deaths, four of them occurred within first 2 wk of admission, one in 3rd wk and 5 within few months of discharge from hospital. CONCLUSIONS: Ventriculitis associated with meningitis is a difficult to treat infection with significant mortality and morbidity. It requires prolonged administration of antibiotics. External ventricular drainage may improve cure rate and hasten clearing of CSF infection.

Excessive external drainage of CSF might aggravate bacterial ventriculitis.

Bacterial ventriculitis is one of the most difficult diseases of neurosurgery, if not controlled well in the early stage, it will cause empyema, adhesion and separated infectious ventricle locules inside the ventricle. Few studies focus on the relationship between external drainage volume and the occurrence of adhesion and separation of the ventricle. This paper reported a case of ventriculitis, and we propose that excessive external drainage might increase the occurrence rate of the internal separation and adhesion of ventricle in patients with ventriculitis. Choosing an appropriate drainage method and avoiding excessive drainage might be the key to the treatment of ventriculitis.

Immediate diagnosis of ventriculits: evaluation of parameters independent of microbiological culture.

BACKGROUND: Generally accepted reference values in CSF diagnostics are not valid in cerebrospinal fluid (CSF) containing large amounts of blood. Residual blood may obscure ventriculitis as diagnostics largely depend on parameters such as cell count, lactic acid and total protein measurement. We sought to improve the diagnostics by evaluating a cytokine panel and soluble CD62L as markers of ventriculitis. In addition, we tested an algorithm of established parameters to predict ventriculitis in a specific patient collective. METHODS: Analysis was performed on ventricular CSF samples from 50 consecutive patients. Gram staining, microbiological culture, total cell count, total protein and CD62L expression on neutrophil granulocytes were analysed immediately. Cytokines and soluble CD62L were measured by flow cytometry. FINDINGS: Positive culture was detected in ten patients. Of all parameters tested only IL1-beta, IL8 and CD62L on neutrophils were significantly different between culture-positive and -negative patients. The highest predictive value was obtained when analysing IL1-beta. The predictive value of a parameter combination (IL6 in CSF, C-reactive protein and leukocytes in periphereal blood) was comparable to IL1-beta. Half of the patients in this analysis were identified as culture positive because of the lack of inflammatory response. CONCLUSIONS: IL1-beta and perhaps also IL8 provide very good analytical performance when looking for ventriculitis in patients with residual blood in CSF. Turn-around time is short, and results could be reported within 1 h for 24 h a day. In some patients application of glucocorticoids may result in restricted inflammatory response. Even in these patients IL1-beta provides a reliable parameter for the immediate diagnosis of ventriculitis.