Population pharmacokinetics and dosing simulations of total and unbound temocillin in the plasma and CSF of neurocritically ill patients with external ventricular drain-related cerebral ventriculitis.

BACKGROUND: Cerebral ventriculitis might be caused by Gram-negative bacteria, including ESBL producers. Temocillin may be a useful treatment option in this scenario; however, no consistent data are available regarding its penetration into the CSF. OBJECTIVES: To describe the population pharmacokinetics of temocillin in plasma and CSF and to determine the probability for different simulated dosing regimens to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in the CSF. METHODS: Ten post-neurosurgical critically ill adult patients requiring continuous drainage of CSF were included in this monocentric, prospective, open-label, non-randomized study. They received 2 g loading dose temocillin over 30 min IV infusion, followed by a 6 g continuous infusion over 24 h. Total and unbound concentrations were measured in plasma (n = 88 and 86) and CSF (n = 88 and 88) samples and used to build a population PK model. Monte Carlo simulations were performed to estimate the PTA at 100% Css>MIC (steady state concentration above the MIC) in CSF. RESULTS: All patients were infected with Enterobacterales with temocillin MICs ≤8 mg/L. The median (min-max) temocillin penetration in CSF was 12.1% (4.3-25.5) at steady state. Temocillin unbound plasma pharmacokinetics were best described by a one-compartment model. PTA for the applied dosing regimen was >90% for bacteria with MIC ≤ 4 mg/L. CONCLUSIONS: The currently approved dose of 6 g by continuous infusion may be adequate for the treatment of ventriculitis by Enterobacterales with MIC ≤ 4 mg/L if considering 100% Css>MIC as the PK/PD target to reach. Higher maintenance doses could help covering higher MICs, but their safety would need to be assessed.

Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report.

BACKGROUND: Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. CASE PRESENTATION: A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient's condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. CONCLUSIONS: Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Systematic review and meta-analysis of intraventricular antibiotics for neonatal meningitis and ventriculitis.

PURPOSE: We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available evidence. METHODS: DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, LILACS, and SCOPUS up to 17 February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized experimental and observational studies were included. The Cochrane methodology was used for systematic reviews. RESULTS: Twenty-six observational studies and one randomized clinical trial involving 272 patients were included. The risk of bias in both pediatric and neurosurgical studies was high, and the quality of evidence was low (evidence level C). In the pediatric studies, no significant differences in mortality were found between intraventricular antibiotics and only systemic antibiotic [25.4% vs 16.1%, OR = 0.96 (0.42-2.24), P = 0.93]. However, when analyzing the minimum administered doses, we found a lower mortality when a minimum duration of 3 days for intraventricular antibiotics was used compared to only systemic antibiotic [4.3% vs 17%, OR = 0.22 (0.07-0.72), P = 0.01]. In the neurosurgical studies, the use of intraventricular antibiotics in ventriculitis generally results in a mortality of 5% and a morbidity of 25%, which is lower than that in cases where intraventricular antibiotics were not used, with an average mortality of 37.3% and a morbidity of 50%. CONCLUSION: Considering the low quality of evidence in pediatric and neurosurgical studies, we can conclude with a low level of certainty that intraventricular antibiotics may not significantly impact mortality in neonatal meningitis and ventriculitis. However, reduced mortality was observed in cases treated with a minimum duration of 3 days of intraventricular antibiotic, particularly the multidrug-resistant or treatment-refractory infections. Higher-quality studies are needed to improve the quality of evidence and certainty regarding the use of intraventricular antibiotics for treating neonatal meningitis and ventriculitis.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses.

OBJECTIVE: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. METHODS: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal-fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non-isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin-eosin-stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0-3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. RESULTS: Thirty-five CMV-infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non-isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non-isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non-isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white-matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non-isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non-isolated halo, histological brain lesions did not progress with gestational age, although white-matter necrosis was more frequent, albeit non-significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). CONCLUSIONS: In CMV-infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white-matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow-up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study.

BACKGROUND: For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. METHODS: Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. RESULTS: Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159-289] mg/L and the CSF concentration 99 [66-144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163-438] mg/L and 104 [65-269] mg/L. Median CSF penetration was 46 [36-59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. CONCLUSION: Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

Talaromyces rugulosus ventriculitis diagnosed by nanopore amplicon sequencing, 2022.

Ventriculitis has serious complications and a high mortality rate, so it is important to early identification of the pathogen for appropriate treatment. We report case of ventriculitis caused by Talaromyces rugulosus, a rare pathogen, in South Korea. Affected patient was immunocompromised. Repeated cerebrospinal fluid culture tests were negative, but the pathogen was identified by fungal internal transcribed spacer amplicon nanopore sequencing. The pathogen was detected outside the endemic area of talaromycosis.

How I do it: brainwashing for purulent ventriculitis.

BACKGROUND: The management of ventriculitis remains controversial, with no single management strategy that can provide a good outcome. There are few articles describing the brainwashing technique, and most for neonatal intraventricular hemorrhage. This technical note is important because it describes a practical way to perform brainwashing in case of ventriculitis, and it is more feasible compared to endoscopic lavage in developing countries. METHOD: We describe in a stepwise fashion the surgical technique of ventricular lavage. CONCLUSION: Ventricular lavage is a neglected technique that can help to improve ventricular infection and hemorrhage prognosis.

Use of α-Defensins to Help Diagnose Nosocomial Ventriculitis.

Ventriculitis is a severe complication of indwelling neurosurgical devices that is associated with significant morbidity and mortality. The incidence rate of ventriculitis is approximately 10% with external ventricular drains. Obstinately, patients with these indwelling neurosurgical devices are prone to have traditional cerebral spinal fluid parameters that lack sensitivity and specificity in diagnosing nosocomial ventriculitis. In addition, diagnosis can be arduous given that indolent pathogens are commonly implicated. Therefore, diagnosis is difficult but paramount to thwart the morbidity and mortality associated with this infectious condition as well as to reduce the prolonged use of broad-spectrum antibiotics. As we extrapolate from prosthetic joint infections, for which diagnosis can also be challenging, we learn that the use of α-defensins as a diagnostic biomarker for nosocomial ventriculitis may hold promise. Herein, the viewpoint of using α-defensins as a diagnostic biomarker for nosocomial ventriculitis is discussed.

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.

Candida meningitis/ventriculitis over a decade. Increased morbidity and length of stay a concern.

AIM: The primary aim of this study was to review the diagnosis, management and outcome of Candida meningitis/ventriculitis in our hospital over a ten-year period. MATERIALS AND METHODS: We retrospectively reviewed all culture and 18s rRNA nucleic acid positive CSF specimens processed between 1st January 2010 and 31st December 2020. Patient records were subsequently reviewed to assess the significance of the isolate. RESULTS: Of 851 culture-positive cerebrospinal fluid (CSF) specimens, Candida spp. were isolated from 29 (3.4%), representing infection in 12 patients. One culture-negative specimen was positive for Candida on 18s rRNA testing. Of the 13 patients, eight were male; 61.5% and the median age was 47 years; range: 20-70. The median interval from admission to onset of infection and culture positivity was 24 days (range: 1-63 days). All patients had a central nervous system (CNS) device in situ (external ventricular drain: 11; ventriculoperitoneal shunt: 1; lumbar drain: 1). Four were colonised with Candida spp. before meningitis/ventriculitis diagnosis, from wounds (n = 3), respiratory (n = 3), and urine (n = 1) specimens. On culture, the most common species was Candida albicans (n = 8), followed by C. parapsilosis (n = 2), C. tropicalis (n = 1), and C. dubliniensis (n = 1). The median number of follow-up CSFs per patient was nine (range; 3-22), with a median of 6 days to CSF sterility (range 3-10 days). Treatment included; liposomal amphotericin B (n = 5), fluconazole (n = 2), liposomal amphotericin B, and flucytosine (n = 2), liposomal amphotericin B, fluconazole and flucytosine (n = 3), and intra-ventricular amphotericin B (n = 1). Median treatment duration was 25 days (range 11-76) and CNS device removal occurred in 12 patients. The median length-of-stay (LOS) was 58 days (range 24-406). On discharge, moderate to severe disability (Modified Rankin Scale [mRS] 3-5) was evident in eight patients. Two patients died and one was lost to follow-up. CONCLUSION: Meningitis/ventriculitis due to Candida spp. is an uncommon but challenging infection, usually associated with a device, increased morbidity, LOS, and necessitating prolonged treatment. Neurosurgeons need to be aware of these issues in managing and in communicating with such complex patients.

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: a Prospective Two-Center Study.

Morbidity and mortality related to ventriculitis in neurocritical care patients remain high. Antibiotic dose optimization may improve therapeutic outcomes. In this study, a population pharmacokinetic model of meropenem in infected critically ill patients was developed. We applied the final model to determine optimal meropenem dosing regimens required to achieve targeted cerebrospinal fluid exposures. Neurocritical care patients receiving meropenem and with a diagnosis of ventriculitis or extracranial infection were recruited from two centers to this study. Serial plasma and cerebrospinal fluid samples were collected and assayed. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. We sought to determine optimized dosing regimens that achieved meropenem cerebrospinal fluid concentrations above pathogen MICs for 40% of the dosing interval, or a higher target ratio of meropenem cerebrospinal fluid trough concentrations to pathogen MIC of ≥1. In total, 53 plasma and 34 cerebrospinal fluid samples were obtained from eight patients. Meropenem pharmacokinetics were appropriately described using a three-compartment model with linear plasma clearance scaled for creatinine clearance and cerebrospinal fluid penetration scaled for patient age. Considerable interindividual pharmacokinetic variability was apparent, particularly in the cerebrospinal fluid. Percent coefficients of variation for meropenem clearance from plasma and cerebrospinal fluid were 41.7% and 89.6%, respectively; for meropenem, the volume of distribution in plasma and cerebrospinal fluid values were 63.4% and 58.3%, respectively. High doses (up to 8 to 10 g/day) improved attainment of meropenem cerebrospinal fluid target exposures, particularly for less susceptible organisms (MICs, ≥0.25 mg/L). Standard meropenem doses of 2 g every 8 h may not achieve effective concentrations in cerebrospinal fluid in all critically ill patients. Higher doses, or alternative dosing methods (e.g., loading dose followed by continuous infusion) may be required to optimize cerebrospinal fluid exposures. Doses of up to 8 to 10 g/day either as intermittent boluses or continuous infusion would be suitable for patients with augmented renal clearance; lower doses may be considered for patients with impaired renal function as empirical suggestions. Ongoing dosing should be tailored to the individual patient circumstances. Notably, the study population was small and dosing recommendations may not be generalizable to all critically ill patients.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Accuracy of heparin-binding protein for the diagnosis of nosocomial meningitis and ventriculitis.

BACKGROUND: The sensitive and accurate diagnosis of nosocomial meningitis and ventriculitis is still a critical problem. This study was designed to explore the diagnostic value of cerebrospinal fluid heparin-binding protein (HBP) in nosocomial meningitis and ventriculitis in comparison with procalcitonin and lactate. METHODS: In this observational study, 323 suspected patients were enrolled, of which 42 participants were excluded because they could not be accurately grouped, 131 subjects who were eventually diagnosed with nosocomial meningitis or ventriculitis and 150 patients in whom infection was ultimately ruled out were included in the final analysis. The main results are expressed as medians (interquartile ranges). The Chi-squared test was used to compare the baseline characteristics. The Mann-Whitney U-test was used for group and subgroup analyses. The area under the receiver operating characteristic curve was calculated to describe the diagnostic accuracy of the biomarkers. Spearman's partial correlation was used to analyze associations between the biomarkers. Statistical significance was set when p value < 0.05. RESULTS: HBP achieved the largest area under the receiver operating characteristic curve, which was 0.99 (95% confidence interval 0.98-1.00) compared with 0.98 (95% confidence interval 0.96-0.99) for lactate and 0.69 (95% confidence interval 0.62-0.75) for procalcitonin. With a cutoff level at 23 ng/mL, HBP achieved a sensitivity of 97%, a specificity of 95%, a positive predictive value of 93% and a negative predictive value of 98%. The levels of HBP presented no significant discrepancy between patients who received previous empiric anti-infective therapy and those who did not (p > 0.05). Higher concentrations of HBP were present in patients with positive microbiological findings (p < 0.05). Levels of HBP positively correlated with polymorphonuclear cell count (Spearman's rho = 0.68, p < 0.01), white blood cell count (Spearman's rho = 0.57, p < 0.01) and lactate (Spearman's rho = 0.34, p < 0.01). CONCLUSIONS: Cerebrospinal fluid heparin-binding protein is a reliable auxiliary diagnostic marker that is preferable over lactate and procalcitonin in identifying nosocomial meningitis and ventriculitis, and it also contributes to solving the diagnostic difficulties caused by empiric antibiotherapy.

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.

Ventriculosubgaleal shunt as a proposed technique for post-infectious hydrocephalus.

BACKGROUND: The management of post-infectious hydrocephalus (PIH) remains challenging for neurosurgeons. It requires a temporary diversion procedure till the normalization of CSF parameters prior to the permanent one. Ventriculosubgaleal shunt (VSGS) was widely used in pediatric cases with post-hemorrhagic hydrocephalus (PHH). However, its role in PIH is still lacking. This study was done to elucidate the safety and efficacy of VSGS as a temporary CSF diversion procedure before the permanent one in patients with PIH. PATIENTS AND METHODS: This retrospective investigation analyzed the data of 50 consecutive cases who underwent VSGS for PIH. RESULTS: The age of the included patients ranged between 1 and 10 months. Twenty-six cases had meningitis and or ventriculitis (52%), while the remaining had shunt infection. At follow-up, arresting of hydrocephalus was noted in ten patients (20%), while another 36 cases required the permanent diversion procedure within 35 days. Regarding the shunt complications, scalp infection, tissue breakdown, and shunt exposure were encountered in ten cases (20%), while CSF leakage was noted in 12 cases (24%). Shunt migration was noted in only two patients (4%). Shunt revision was needed in 16 cases (32%). Mortality was encountered in four cases (8%) because of sepsis. Risk factors for morbimortality included younger age, lower weight, male gender, and meningitis and or ventriculitis. CONCLUSION: VSGS is a safe and effective procedure in infants awaiting definitive VPS for postinfectious hydrocephalus. It was proven that VSGS has shortened the hospital stay and the economic burden on the country.

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.

Disseminated protothecosis with central nervous system involvement in a dog in New Zealand.

CASE HISTORY: A 1-year-old Border Terrier presented with acute onset of neurological signs and neck pain. CLINICAL FINDINGS: Severe generalised ataxia, muscle tremors and cranial nerve deficits were noted. Multifocal brain lesions were suspected based on neurological examination. Computed tomography revealed an abdominal mass and cerebellar herniation through the foramen magnum. LABORATORY AND PATHOLOGICAL FINDINGS: Cytological and histopathological analysis of the abdominal mass revealed necrotising and granulomatous lymphadenitis with intralesional algal elements most consistent with Prototheca spp.. Culture of a sample from the mesenteric lymph node confirmed the presence of Prototheca spp. which was identified as P. bovis based on sequencing of a DNA fragment amplified by PCR. Following inadequate response to symptomatic therapy and poor prognosis, the dog was subjected to euthanasia. Histopathological evaluation of the central nervous system lesions, identified granulomatous meningitis and ventriculitis with the presence of intralesional algae. DIAGNOSIS: Disseminated protothecosis with granulomatous meningitis and ventriculitis caused by Prototheca bovis (formerly P. zopfii gen. 2). CLINICAL RELEVANCE: This is the first case report of disseminated protothecosis with central nervous system involvement in a dog in New Zealand.

Population pharmacokinetics of vancomycin in patients with external ventricular drain-associated ventriculitis.

BACKGROUND: To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)-associated ventriculitis, the pharmacokinetics of vancomycin were evaluated and covariate relationships explored. METHODS: For the population pharmacokinetic model patients were recruited in a neurocritical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of EVD-associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM. RESULTS: A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three-compartment model with linear elimination. Creatinine clearance (ClCr ) and CSF-lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on ClCr and furthermore the clearance (Cldif ) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM: Cl = 5.15 L/h, Q (intercompartmental clearance) = 3.31 L/h, Cldif  = 0.0031 L/h, Vcentral  = 42.1 L, VCSF  = 0.32 L and the value of Vperipheral was fixed to 86.2 L. With the developed pharmacokinetic model, area under the curve (AUC) values as well as CSF trough levels were simulated. CONCLUSION: Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from ClCr ).

Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis.

BACKGROUND: This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis. METHODS: This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose. RESULTS: Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC24h) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004). CONCLUSIONS: Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.