Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill patients-a prospective cohort study.

Meropenem penetration into the cerebrospinal fluid (CSF) is subject to high interindividual variability resulting in uncertain target attainment in CSF. Recently, several authors recommended administering meropenem as a continuous infusion (CI) to optimize CSF exposure. This study aimed to compare the concentrations and pharmacokinetics of meropenem in CSF after intermittent infusion (II) and CI. This prospective, observational study (NCT04426383) included critically ill patients with external ventricular drains who received either II or CI of meropenem. Meropenem pharmacokinetics in plasma and CSF were characterized using population pharmacokinetic modeling (NONMEM 7.5). The developed model was used to compare the concentration-time profile and probability of target attainment (PTA) between II and CI. A total of 16 patients (8 CI, 8 II; samples: nplasma = 243, nCSF = 263) were recruited, with nine patients (5 CI, 4 II) suffering from cerebral and seven patients from extracerebral infections. A one-compartment model described the plasma concentrations adequately. Meropenem penetration into the CSF (partition coefficient (KP), cCSF/cplasma) was generally low (6.0%), exhibiting substantial between-subject variability (coefficient of variation: 84.0%). There was no correlation between the infusion mode and KP, but interleukin (IL)-6 measured in CSF showed a strong positive correlation with KP (P < 0.001). Dosing simulations revealed no relevant differences in CSF concentrations and PTA in CSF between CI and II. Our study did not demonstrate increased penetration rates or higher concentrations of meropenem in the CSF with CI compared with II. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04426383.

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.

Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Development of an Evidence-based Care Bundle for Prevention of External Ventricular Drain-related Infection: Results of a Single-center Prospective Cohort Study and Literature Review.

Background: External ventricular drain (EVD)-related infection (ERI) is a common complication in cranial neurosurgery practice with high mortality. The risk factors associated with ERI are not well studied in low- and middle-income countries (LMIC) like India. Identifying the risk variables is a necessity to design robust evidence-based care bundles for ERI prevention. Materials and methods: This is a single-center prospective cohort study. Patients with and without ERI during the 2-year study period were analyzed along with literature review to identify the risk variables associated with ERI. The Institute for Healthcare Improvement (IHI) comprehensive flowchart was used to develop the concept care bundle for ERI prevention. Results: A total of 211 EVD were inserted during the study period. 15 ERI (7.1%) were identified based on IDSA criteria, with an average infection rate of 11.12 per 1000 EVD days. Gram negative bacteria (GNB) were the predominant pathogen (12/15, 80%), with Klebsiella pneumoniae (6/15, 40%) being the most common bacteria isolated. In multivariate analysis, the risk variables associated with ERI were use of broad spectrum pre-surgical antimicrobial prophylaxis for long duration, choice of posterior craniometric points for EVD insertion, EVD duration >7 days, EVD leak and surveillance cerebrospinal fluid (CSF) sampling at periodic intervals. Based on the risk variables identified in this study and literature review, a consensus decision on the care elements for the insertion and maintenance phases was chosen for the concept care bundle for ERI prevention. Conclusion: An evidence-based concept care bundle for ERI prevention is proposed for further multicentric evaluation and validation. How to cite this article: Ponnambath DK, Divakar G, Mamachan J, Biju S, Raja K, Abraham M. Development of an Evidence-based Care Bundle for Prevention of External Ventricular Drain-related Infection: Results of a Single-center Prospective Cohort Study and Literature Review. Indian J Crit Care Med 2024;28(8):760-768.

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain.

Vancomycin is a commonly used antibacterial agent in patients with primary central nervous system (CNS) infection. This study aims to examine predictors of vancomycin penetration into cerebrospinal fluid (CSF) in patients with external ventricular drainage and the feasibility of CSF sampling from the distal drainage port for therapeutic drug monitoring. Fourteen adult patients (9 with primary CNS infection) were treated with vancomycin intravenously. The vancomycin concentrations in blood and CSF (from proximal [CSF_P] and distal [CSF_D] drainage ports) were evaluated by population pharmacokinetics. Model-based simulations were conducted to compare various infusion modes. A three-compartment model with first-order elimination best described the vancomycin data. Estimated parameters included clearance (CL, 4.53 L/h), central compartment volume (Vc, 24.0 L), apparent CSF compartment volume (VCSF, 0.445 L), and clearance between central and CSF compartments (QCSF, 0.00322 L/h and 0.00135 L/h for patients with and without primary CNS infection, respectively). Creatinine clearance was a significant covariate on vancomycin CL. CSF protein was the primary covariate to explain the variability of QCSF. There was no detectable difference between the data for sampling from the proximal and the distal port. Intermittent infusion and continuous infusion with a loading dose reached the CSF target concentration faster than continuous infusion only. All infusion schedules reached similar CSF trough concentrations. Beyond adjusting doses according to renal function, starting treatment with a loading dose in patients with primary CSF infection is recommended. Occasionally, very high and possibly toxic doses would be required to achieve adequate CSF concentrations, which calls for more investigation of direct intraventricular administration of vancomycin. (This study has been registered at ClinicalTrials.gov under registration no. NCT04426383).

Impact of an external ventricular shunt (EVD) handling protocol on secondary meningitis rates: a historical cohort study with propensity score matching.

BACKGROUND: External ventricular drainage (EVD) is frequently used in neurosurgical procedures for cerebrospinal fluid (CSF) drainage. It is, however, associated with high infection rates, namely secondary meningitis and ventriculitis. Based on a previous high prevalence of these infections among patients with EVDs, we have proposed and implemented a protocol in an effort to decrease the infection rate. The aim of this study was to measure the effect of hospital-wide implementation of the EVD handling protocol on secondary EVD infections. PATIENTS AND METHODS: We included 409 consecutive patients who received a new EVD for other indications than infectious pathologies from January 2000 until June 2012. Patients above 18 years of age were divided into pre- (n = 228) and post-protocol (n = 181) groups. Patient and disease demographics, as well as EVD data together with confounders for secondary meningitis were recorded in a database. Propensity score matching was then performed to create groups matched for sex, age, reason for drainage, type of shunt, time in situ and duration of surgery to place the EVD. Binomial logistic regression for confounder adjustment and regression discontinuity analyses were then performed on the matched cohort. RESULTS: Infections occurred more frequently in the pre-protocol group (23% vs 9%, p <  0.001). The incidence of infection was 33/1000 drain-days pre-protocol and 9/1000 drain-days post-protocol. Regression analysis in a propensity score-matched cohort (n = 103 in the pre- and n = 178 in the post-protocol groups) showed that the pre-protocol period was independently associated with more infections (OR 2.69; 95%-CI 1.22-5.95, p = 0.01). CONCLUSIONS: The incidence of secondary EVD infections can be reduced significantly by the implementation of a strict hospital-wide EVD handling protocol.

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.

CNS infection in children with brain tumors: adding ventriculostomy to brain tumor resection increases risk more than 20-fold.

PURPOSE: To investigate the risk of central nervous system (CNS) infections in children undergoing neurosurgery for brain tumors. METHODS: Single-center retrospective cohort study including all children with brain tumors undergoing neurosurgical treatment over an 11-year period. RESULTS: A total of 274 patients undergoing 733 neurosurgical procedures were included. Overall, 12.8% of patients were diagnosed with a CNS infection during their course of treatment. CNS infections were more frequent among children treated with CSF diversion (p < 0.001) and independently associated with low age (OR/y 0.9 (CI 95% 0.769-0.941), intraventricular (OR 2.8, CI 95% 1.2-6.5), and high-grade tumors (OR 2.7, CI 95% 1.1-6.5). The majority of CNS infections occurred within 30 days of surgery, resulting in a postoperative CNS infection rate of 5.3%. Postoperative CNS infections were significantly more frequent following adjunct EVD placement during tumor resection compared to a stand-alone craniotomy (30.4% vs. 1.5%, RR 20.6, CI 95% 5.7-72.2). CONCLUSION: CNS infections affect at least 12% of children with brain tumors and are associated with age, tumor location, and grade. Adding EVD to tumor surgery increases the risk of postoperative CNS infection, and reconsidering routine adjunct EVD placement is therefore advocated.

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.

Broad Range Eubacterial Polymerase Chain Reaction of Cerebrospinal Fluid Reduces the Time to Exclusion of and Costs Associated with Ventriculostomy-Related Infection in Hemorrhagic Stroke.

BACKGROUND: Patients with hemorrhagic stroke and an external ventricular drain in situ are at risk for ventriculostomy-related-infections (VRI). Because of the contamination of the cerebrospinal fluid (CSF) with blood and the high frequency of false negative CSF culture, the diagnosis of VRI remains challenging. This study investigated the introduction of CSF broad range eubacterial polymerase chain reaction (ePCR) and its effect on frequency and duration of antibiotic therapy for VRI, neurocritical care unit (NCCU) length of stay, related costs, and outcome. METHODS: Between 2020 and 2022, we prospectively included 193 patients admitted to the NCCU of the University Hospital of Zürich with hemorrhagic stroke and an external ventricular drain for more than 48 h. Patient characteristics, serum inflammatory markers, white blood cell count in CSF, use and duration of antibiotic treatment for VRI, microbiological findings (CSF cultures and ePCR tests), and NCCU length of stay were compared in patients with no infection, noncerebral infection, suspected VRI, and confirmed VRI. Data of patients with suspected VRI of this cohort were compared with a retrospective cohort of patients with suspected VRI treated at our NCCU before the introduction of CSF ePCR testing (2013-2019). RESULTS: Out of 193 patients, 12 (6%) were diagnosed with a confirmed VRI, 66 (34%) with suspected VRI, 90 (47%) with a noncerebral infection, and 25 (13%) had no infection at all. Compared with the retrospective cohort of patients, the use of CSF ePCR resulted in a reduction of patients treated for suspected VRI for the whole duration of 14 days (from 51 to 11%). Furthermore, compared with the retrospective group of patients with suspected VRI (n = 67), after the introduction of CSF ePCR, patients with suspected VRI had shorter antibiotic treatment duration of almost 10 days and, hence, lower related costs with comparable outcome at 3 months. CONCLUSIONS: The use of CSF ePCR to identify VRI resulted in shorter antibiotic treatment duration without changing the outcome, as compared with a retrospective cohort of patients with suspected VRI.

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.

Post-neurosurgical Nocardia meningoventriculitis: a case report and review of the literature.

The genus Nocardia consists of a group of gram-positive environmental bacteria. They typically cause lung and brain infections in immunocompromised patients, even though one out of three infected patients have a normally functioning immune system. Being a ubiquitous microorganism, in some cases Nocardia has been associated with nosocomial acquired infections and surgical procedures. A review of the literature in this field follows the case report. A 47-year-old woman underwent an endoscopic third ventriculostomy and a left retro-sigmoid craniotomy for a schwannoma removal. Meningeal symptoms began a week later, in association with C reactive protein rise and leukocytosis. Cerebrospinal fluid (CSF) examination was clear with hypoglycorrhachia, hyperprotidorrachia and polymorphonuclear cells. Cultural exam was negative. At the brain magnetic resonance imaging (MRI) purulent material was described in the occipital ventricular horns. Empirical broad spectrum antibiotic therapy was given for 31 days until the brain MRI showed a resolution of the infection. Ten days later, the patient was admitted to the hospital because of new meningeal symptoms. Cerebrospinal fluid culture and Polymerase-chain reaction (PCR) Multiplex for the most important meningitis viruses and bacteria tested negative. A broad-spectrum antibiotic therapy was started with no benefit; thus, a broad-spectrum antifungal therapy was added with little success on clinical status. Meanwhile, a 16s and 18s rRNA PCR was executed on a previous Cerebrospinal fluid with negative results, excluding bacterial and fungal infections. For this reason, all the therapies were stopped. After a few days, high fever and meningeal signs reappeared. The brain MRI showed a meningoventriculitis. An Ommaya catheter with reservoir was inserted and the drawn CSF resulted in the growth of Nocardia farcinica. Antibiogram-based antibiotic therapy was started with intravenous imipenem and trimethoprim-sulfamethoxazole, showing clinical benefit. The patient was sent home with oral linezolid and amoxicillin/clavulanate for a total of 12 months of therapy. Nocardia rarely causes post-neurosurgical complication in a nosocomial setting. This case shows the difficulty in detecting Nocardia and the importance of the correct microbiological sample and antibiogram-based antibiotic therapy to achieve successful treatment.

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.

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.

Diagnostic criteria of CNS infection in patients with external ventricular drainage after traumatic brain injury: a pilot study.

BACKGROUND: Ventriculostomy-related infection (VRI) is a common complication in patients with traumatic brain injury (TBI) treated with an external ventricular drain (EVD). The aim of this study was to investigate incidence and characteristics of patients with VRI, and to explore diagnostic criteria to confidently rule out VRI in patients with TBI. METHODS: This retrospective cohort pilot study included adults with severe TBI who were admitted to the ICU and received an EVD, during a 26-month period. Patients were categorized as having Culture-positive VRI, Culture-negative VRI, or No VRI. Variables that were potentially associated with Culture-positive VRI was analyzed, and predictive values were calculated. RESULTS: 75 of 215 patients with severe TBI (35%) underwent EVD placement; nine of these (12%) were classified as Culture-negative VRI and eight (11%) as Culture-positive VRI. The CSF cell counts that led to VRI treatment were compared with 46 CSF cell counts from No VRI patients. A CSF/plasma glucose ratio below 0.6 had a negative predictive value (NPV) for culture-verified VRI of 0.97 (95% CI: 0.85-1), whereas a combination of three CSF-derived biomarkers within the reference limits (white/red blood cell ratio, CSF/plasma glucose ratio, and protein content) ruled out Culture-positive VRI in this cohort (PPV 0, 95% CI: 0-0.14). C-reactive protein did not reliably predict VRI. CONCLUSIONS: In this pilot study of patients after severe, a combination of biomarkers within reference limits ruled out VRI (PPV 0, CI: 0-0.14). Hypoglycorrhachia was a sensitive marker of VRI (NPV 0.97, CI: 0.85-1). Systemic signs and markers of infection did not predict VRI.

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.

Experience with enterococcal meningitis/ventriculitis in children.

BACKGROUND: Enterococcal infections are increasingly common in hospitalized patients. Enterococcal meningitis/ventriculitis (EMV) is an extremely rare condition of enterococcal infections, occurring particularly in children. This study investigated the clinical and microbiological characteristics, predisposing factors, and prognosis in pediatric patients with EMV. METHODS: Pediatric patients (<18 years) diagnosed with EMV were retrospectively evaluated over 10 years. RESULTS: The study included a total of 25 isolates from 24 patients, median age 23 months (range: 1-136 months). The most common symptoms included vomiting, fever, and headache, with hydrocephalus shunt and preterm birth being the two most common conditions. Commonly associated infections, with central nervous system (CNS) devices as a predisposing factor, were due to external ventricular drainage and ventriculoperitoneal shunts. Two patients with spontaneous meningitis were preterm infant. Of the isolates, 44% were Enterococcus faecalis, 44% E. faecium, and 12% E. gallinarum. Five (20%) isolates were vancomycin resistant. Twelve patients were resistant to anti-enterococcal antibiotics, including ampicillin, ciprofloxacin, imipenem, teicoplanin, gentamicin, and linezolid (40%, 20%, 8%, 8%, 4%, and 4%, respectively). Enterococcus faecium was more resistant to ampicillin, ciprofloxacin, teicoplanin, and vancomycin than E. faecalis. The median treatment duration was 17 days (interquartile range: 14-26 days).The mortality rate was 8.3% (2/24; both associated with vancomycin resistance). CONCLUSIONS: Neurosurgical conditions are the most common predisposing factors for EMV. Preterm birth is an important predisposing factor in children. Because EMV is nonspecific in clinical findings, it should be considered when there is an underlying CNS disorder and empirical treatment should begin in this direction.

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.