Serial Neuroendoscopic Lavage for the Treatment of Elevated Cerebrospinal Fluid Protein Levels in Infants with Gram-Negative Rod Ventriculitis.

INTRODUCTION: Gram-negative rod (GNR) bacterial ventriculitis is a rare complication of shunt-dependent hydrocephalus, often requiring an extended and invasive treatment course. Accumulation of purulent material, as well as empyema and septation formation, limits circulation of antibiotics and infection clearance. Supplementation of standard care with neuroendoscopic-guided intraventricular lavage with lactated Ringer solution and fenestration of septations may facilitate infection clearance and simplify the eventual shunt construct required. Here, the utility of serial lavage for ventriculitis is described in a population of shunt-dependent neonates and infants at high risk for morbidity and mortality. METHODS: Five infants with shunt-dependent hydrocephalus and subsequent GNR ventriculitis were treated with standard care measures with the addition of serial neuroendoscopic lavage. A retrospective chart review was performed to collect patient characteristics, shunt dependency, and shunt revisions within a year of ventriculitis resolution. RESULTS: Patients demonstrated a mean 74% decrease in cerebrospinal fluid (CSF) protein following each neuroendoscopic lavage and trended toward a shorter time to infection clearance in comparison to previously published literature. Patients required 0-2 shunt revisions at 1-year follow-up following hospitalization for shunt-related ventriculitis (mean 0.8 +/- 0.8). CONCLUSIONS: Serial neuroendoscopic lavage is an effective technique, used alone or in combination with fenestration of septations, to reduce the CSF protein and bacterial load in the treatment of ventriculitis, decreasing time until eradication of infection. Serial lavage may reduce the risk of future shunt malfunction, simplify the future shunt construct, and decrease duration of infection.

Neuroendoscopic lavage for the treatment of pyogenic ventriculitis in children: personal series and review of the literature.

INTRODUCTION: Pyogenic ventriculitis is a severe infection of the central nervous system with serious and often irreversible consequences in the quality of life of patients. Its treatment is difficult due to the impossibility of achieving sterility of cerebrospinal fluid (CSF) and the physiological characteristics promptly. Several treatment options have been described, from prolonged antibiotic treatments to placement of ventricular drains with continuous irrigation and puncture reservoirs. We propose an aggressive and minimally invasive treatment with neuroendoscopic lavage (NEL). METHODS: Retrospective and descriptive study. We analyzed the NEL performed in our hospital for pyogenic ventriculitis between 2011 and 2020. A total of 16 patients were found; 2 of them lost follow-up, so they were not included. All patients had a diagnosis of pyogenic ventriculitis, either due to the macroscopic characteristics of the CSF or due to imaging criteria. Between 1 and 3 NEL were performed per patient until obtaining sterility and normalization of protein and cell counts of CSF. RESULTS: The average age was 38 months (2 months to 16 years). Ten patients were female and 4 were male. Sixty-four percent of germs in cultures corresponded to gram-negative and polymicrobial flora. The average number of days until the first sterile CSF post-NEL was 3.8 days (0 to 10 days). The NEL produced a significant improvement in the characteristics of the CSF compared to the pre-NEL. The mean pre-NEL of CSF protein levels was 907 mg/dl (123-4510 mg/dl) compared with the post-NEL of 292 mg/dl (38-892 mg/dl) with a p-value = 0.0076. Regarding cellularity, statistically significant results were also achieved (p-value = 0.0011) with a pre-surgical cellularity of 665 elements/mm3 (4-3090 elements/mm3) compared with 57 elements/mm3 (0-390 elements/mm3) post-NEL. Of the patients, 85.7% had a shunt prior to the onset of ventriculitis and the average number of days until the new shunt was 36.56 days (17-79 days), with a total hospitalization days ranging from 22 to 170. CONCLUSIONS: NEL allows rapid sterilization of CSF, decreasing the deleterious effect of infection in the CNS more rapidly compared to other types of conventional treatment.

Dynamic Intracranial Pressure Waveform Morphology Predicts Ventriculitis.

BACKGROUND: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis. METHODS: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported. RESULTS: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert. CONCLUSIONS: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling.

Neutrophil CD64 index in cerebrospinal fluid as a marker of bacterial ventriculitis in children with external ventricular drainage.

BACKGROUND: Bacterial ventriculitis is a common complication in children with temporary external ventricular drains (EVD) and the diagnosis is challenging. The present study compared the diagnostic accuracy of novel cerebrospinal fluid (CSF) marker - CD64 expression on neutrophils measured as neutrophil CD64 index (CD64in) to routine laboratory CSF and blood markers for bacterial ventriculitis in children with EVD. METHODS: We conducted a prospective, observational study, enrolling children with EVD. CD64in in CSF together with CSF markers (leukocyte count, percentage of neutrophils, glucose, and proteins) and blood markers (leukocyte and differential count, C-reactive protein (CRP), and procalcitonin (PCT)) were studied at the time of suspected bacterial ventriculitis. CD64in was measured by flow cytometry. Diagnostic accuracy determined by the area under the receiver-operating characteristic (ROC) curves (AUC) was defined for each marker. RESULTS: Thirty-three episodes of clinically suspected ventriculitis in twenty-one children were observed during a 26-month period. Episodes were classified into those with microbiologically proven ventriculitis (13 episodes) and into those with microbiologically negative CSF (20 episodes). CD64in and leukocyte count were the only CSF markers that could differentiate between groups with diagnostic accuracy of 0.875 and 0.694, respectively. Among blood markers only CRP and band neutrophils differentiated between groups with diagnostic accuracy of 0.792 and 0.721, respectively. CONCLUSIONS: CD64in in CSF is a promising diagnostic marker of bacterial ventriculitis in children with EVD as it has higher diagnostic accuracy than routine blood and CSF markers for diagnosing bacterial ventriculitis at the time of clinical suspicion.

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.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria.

The aim of the study is to explore the experiences in diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the clinical intervention, and the patients' prognosis were evaluated. The bacterial smears of ventricular drainage from all the cases were G- bacteria. Head CT and MRI scans confirmed that they were intraventricular empyema. Eighteen cases of CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive, 1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive. One case of the bacterial culture was negative. All patients were treated by using intraventricular lavage in combination with intravenous and intraventricular antibiotics in accordance with the clinical conditions. After treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%). Eight patients who were cured had received ventriculoperitoneal shunt due to hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were persistent in vegetative state starting before the infection; they did not show any improving consciousness after infection had been cured. Suppurative ventriculitis in severe neurosurgical patients is mainly infected by G- with a higher mortality. Early diagnosis, especially in identifying pathogen types, timely ventricular irrigation, and ventricular drainage together with intravenous and intraventricular antibiotic treatment, should improve prognosis.

Clinical and Laboratory Characteristics for the Diagnosis of Bacterial Ventriculitis After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The diagnosis of nosocomial bacterial ventriculitis in patients with subarachnoid hemorrhage (SAH) can be challenging. METHODS: We performed a retrospective study on the diagnostic accuracy of clinical and laboratory characteristics for the diagnosis of bacterial ventriculitis in 209 consecutive patients with an aneurysmal SAH admitted in a tertiary referral center from 2008 to 2010. Diagnostic value of clinical characteristics and inflammatory indexes in CSF and blood were determined for three diagnostic categories: (1) no suspicion for bacterial ventriculitis; (2) clinical suspicion for bacterial ventriculitis, defined as initiation of empirical antibiotic treatment for ventriculitis, but negative CSF cultures; and (3) CSF culture-positive bacterial ventriculitis. RESULTS: Empirical antibiotics for suspected ventriculitis was initiated in 48 of 209 (23 %) patients. CSF cultures were positive in 11 (5 %) patients. Within the group of suspected ventriculitis, only longer duration of CSF drainage and lower CSF red blood cell counts predicted for culture positivity. None of the other clinical features or inflammatory indexes in CSF and blood were associated with culture-proven bacterial ventriculitis. CONCLUSIONS: Nosocomial bacterial ventriculitis in patients with aneurysmal SAH is often suspected but confirmed by culture in a minority of cases. Improvement of diagnostics for nosocomial bacterial ventriculitis in patients with aneurysmal SAH is needed.

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.

Measurement of cerebrospinal fluid lactate levels in pediatric patients with suspected ventriculoperitoneal shunt infection: A retrospective cohort study.

INTRODUCTION: Ventriculoperitoneal shunt (VPS) infection is a severe complication. Early diagnosis could help to decrease morbidity and treatment costs. Lactate has been used for the diagnosis of other central nervous system infections. The aim of this study is to determine the usefulness of lactate for the diagnosis of VPS infection. METHODOLOGY: Retrospective cohort study. Lactate was measured in patients who consulted with VPS dysfunction between May 2019 and May 2022. Mean were compared according to culture results. A Receiver Operating Characteristic (ROC) curve was performed to determine the appropriate cut-off point. RESULT: Lactate has a high negative predictive value but a low positive predictive value for the diagnosis of ventriculitis.

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.

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.

Ventriculitis associated with extraventricular drainage: etiology, diagnosis and treatment focused on neurocritic care units.

Ventriculitis after extraventricular drainage is a very important neurosurgical complication in neurocritical care units. It is necessary to make an early diagnosis, given that the morbidity and mortality secondary to it can be variable, and complicate the evolution of neurocritical patients. Despite this, ventriculostomy continues to be an important pillar in monitoring and treatment. Given the urgency of ventriculitis associated with multiresistant germs, new antimicrobial drugs have emerged as part of the treatment, as intraventricular routes have been proposed within the new investigations. However, the foregoing does not yet have sufficient bases to be able to support it. The present review was carried out with the aim of contributing to an early diagnosis and treatment of ventriculitis associated with extra ventricular drainage in neurocritical patients, and in this way to contribute to improve survival and prevent fatal outcomes in these patients.

La ventriculitis posterior a un drenaje extraventicular constituye una complicación neuroquirúrgica muy importante en las unidades de cuidados neurocríticos. Se hace necesario realizar un diagnóstico precoz, dado que la morbimortalidad secundaria a esta puede ser variable y complicar la evolución de los pacientes neurocríticos. A pesar de esto, la ventriculostomía continúa siendo un pilar importante en el monitoreo y el tratamiento. Ante la urgencia de ventriculitis asociadas a gérmenes multirresistentes han surgido nuevos fármacos antimicrobianos como parte del tratamiento, al igual que se han propuesto vías intraventriculares dentro de las nuevas investigaciones. Sin embargo, lo anterior aún no tiene bases suficientes para poder ­sustentarlo. La presente revisión se realizó con el objetivo de contribuir a un diagnóstico precoz y al tratamiento de la ventriculitis asociada a drenaje extraventricular en pacientes neurocríticos, y de esta forma poder mejorar la sobrevida y prevenir desenlaces fatales en estos pacientes.

Standardized Ventriculostomy Protocol without an Occlusive Dressing: Results of an Observational Study in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Catheter-related infections are a potentially life-threatening complication of having an external ventricular drain (EVD). Patients with aneurysmal subarachnoid hemorrhage (aSAH) are at increased risk of infection associated with prolonged ventricular drainage, with a reported mean infection rate of 6%. We report the EVD-associated infection rate among patients with aSAH managed with a unique standardized treatment protocol without an occlusive EVD dressing. METHODS: Patients with aSAH admitted from August 2015 through August 2017 were retrospectively analyzed for EVD placement. Cerebrospinal fluid (CSF) samples were obtained twice weekly for culture and routine studies. EVD-associated infection was defined as growth of CSF cultures. RESULTS: During the 2-year study period, 122 patients presented with an aSAH, with 91 (74.6%) having EVD placement. In patients with EVDs, the mean age was 57.9 years (68% women); 88% of aSAHs were Fisher grade III or IV. Mean duration of EVD was 14 days, and 13% of patients required EVD replacement. Endovascular coiling and surgical clipping were performed in 34 (37%) and 53 (58%) patients with EVD, respectively. A total of 347 CSF studies were performed with no EVD-associated infections. There were 3 CSF samples with false-positive Gram stain results but no growth on concurrent or multiple repeat cultures. CONCLUSIONS: Using a standardized protocol for placement and management of EVDs in patients with aSAH is associated with low risk of CSF infection. Our study demonstrates that occlusive EVD dressings are not necessary and that routine CSF sampling in patients with EVD may lead to false-positive findings and unnecessary antibiotic administration.

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.

Inflammatory Markers in Serum and Cerebrospinal Fluid for Early Detection of External Ventricular Drain-associated Ventriculitis in Patients With Subarachnoid Hemorrhage.

BACKGROUND: External ventricular drain (EVD)-associated ventriculitis is a serious complication. Early diagnosis can be difficult particularly in critically ill patients with aneurysmal subarachnoid hemorrhage (aSAH). We examined the diagnostic potential of standard serum and cerebrospinal fluid (CSF) biomarkers to differentiate between EVD-associated infections and aseptic courses in patients with aSAH. MATERIALS AND METHODS: We retrospectively evaluated the levels of inflammatory markers in serum (white blood cell count, percentage of neutrophils [sN%], and procalcitonin) and CSF (total leukocyte count [CSFTLC], CSFglucose, CSF/serumglucose ratio, CSF total protein [CSFTP]) of 63 consecutive patients with aSAH. Receiver operating characteristic curves and the area-under-the-curve (AUC) were calculated to detect the diagnostic potential, optimized threshold, sensitivity (SE), specificity (SP), + likelihood ratio (LR), and -LR of each biomarker. RESULTS: Of all patients, 17 (27%) developed an EVD-associated ventriculitis within a mean of 7.8±2.3 days after implantation. sN% had a very good diagnostic potential (AUC=0.900, SE=70.0%, SP=100%), followed by the CSFTLC with good diagnostic potential (AUC=0.841, SE=75.0%, SP=88.5%), and the CSFTP with moderate diagnostic potential (AUC=0.772, SE=73.3%, SP=76.0%). sN% higher than 70% and a CSFTLC higher than 635/µL were highly associated with the diagnosis of ventriculitis (+LR=∞ and 6.5), sN%<70% or a CSFTLC<635 made a diagnosis of ventriculitis unlikely (-LR=0.3 and 0.28). CONCLUSIONS: Routine determination of N% and CSFTLC are useful to distinguish ventriculitis from aseptic courses in the acute phase after aSAH and regardless of the bacteriological test result.

Intra-cerebrospinal fluid antibiotics to treat central nervous system infections: A review and update.

Central nervous system infections can be complications of neurosurgical procedures or can occur spontaneously, and occasionally lead to devastating neurological complications, increased rate of mortality, and lengthier stays in the hospital, subsequently increasing costs. The use of intrathecal antibiotics to bypass the blood brain barrier and provide effective concentrations to the central nervous system has been described as an adjunct treatment option. However, the regimens of antibiotics utilized intrathecally have not been standardized. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2017 and after removing duplicates and checking for relevancy, the final number of articles yielded was 200. This review summarizes the use of antibiotics intrathecally to treat CNS infections, the dosages, therapeutic efficacies, and highlights significant side effects. The current rates of mortality in patients suffering from CNS infections is high, thus intrathecal antibiotic therapy should be considered as a potential therapeutic strategy in this patient population. Multiple antibiotics have demonstrated safety and efficacy when used intrathecally, and further studies, including clinical trials, need to be performed to elucidate their full therapeutic potential and outline proper dosing regimens.

Antibiotic Distribution into Cerebrospinal Fluid: Can Dosing Safely Account for Drug and Disease Factors in the Treatment of Ventriculostomy-Associated Infections?

Ventriculostomy-associated infections, or ventriculitis, in critically ill patients are associated with considerable morbidity. Efficacious antibiotic dosing for the treatment of these infections may be complicated by altered antibiotic concentrations in the cerebrospinal fluid due to variable meningeal inflammation and antibiotic properties. Therefore, doses used to treat infections with a higher degree of meningeal inflammation (such as meningitis) may often fail to achieve equivalent exposures in patients with ventriculostomy-associated infections such as ventriculitis. This paper aims to review the disease burden, infection rates, and common pathogens associated with ventriculostomy-associated infections. This review also seeks to describe the disease- and drug-related factors that influence antibiotic distribution into cerebrospinal fluid and provide a critical appraisal of current dosing of antibiotics commonly used to treat these types of infections. A Medline search of relevant articles was conducted and used to support a review of cerebrospinal fluid penetration of vancomycin, including critical appraisal of the recent paper by Beach et al. recently published in this journal. We found that in the intensive care unit, ventriculostomy-associated infections are the most common and serious complication of external ventricular drain insertion and often result in prolonged patient stay and increased healthcare costs. Reported infection rates are extremely variable (between 0 and 45%), hindered by the inherent diagnostic difficulty. Both Gram-positive and Gram-negative organisms are associated with such infections and the rise of multi-drug-resistant pathogens means that effective treatment is an ongoing challenge. Disease factors that may need to be considered are reduced meningeal inflammation and the presence of critical illness; drug factors include physiochemical properties, degree of plasma-protein binding, and affinity to active transporter proteins present in the blood-cerebrospinal fluid barrier. The relationship between cerebrospinal fluid antibiotic exposures in the setting of ventriculostomy-associated infection and clinical response has not been fully elucidated for many of the antibiotics commonly used in its treatment. More thorough and clinically relevant investigations are needed to better define blood pharmacokinetic/pharmacodynamics targets and optimal therapeutic exposures for treatment of ventriculostomy-associated infections. It is hoped that this future research will be able to provide clearer recommendations for clinicians frequently faced with dosing-related dilemmas when treating patients with these challenging infections.