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.

A pilot study for evaluating the feasibility of using alpha-defensin to support the diagnosis of ventriculitis.

OBJECTIVES: Nosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. METHODS: From May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. RESULTS: There was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. CONCLUSION: This pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis.

Pearls & Oy-sters: Diagnosis and Subtyping of Listeria Ventriculitis in an Immunocompetent Host.

Listeria monocytogenes is a Gram-positive food-borne pathogen that causes gastrointestinal symptoms and CNS infection in susceptible hosts. Two lineages of Listeria cause the majority of neurolisteriosis in humans. In this report, we discuss a case of a 23-year-old previously healthy woman who presented with acute-onset rapidly progressive altered mental status after eating undercooked meats at a local restaurant. Given her age and lack of comorbidities, bacterial meningitis was suspected, and she was treated with ceftriaxone, vancomycin, and steroids. MRI of the brain was consistent with meningitis and ventriculitis; CSF analysis also suggested bacterial meningitis. Despite mechanical ventilation, pressors, and ventricular drain placement, she quickly decompensated and died 12 hours after arrival. CSF culture later returned positive for Listeria monocytogenes We used whole-genome sequencing and near-source comparison to identify the Listeria subtype that led to her unexpected presentation. The results suggest that her CSF isolate was consistent with a lineage II Listeria serotype, which is known to exhibit greater genetic variation than the more commonly isolated lineage I serotypes. We conclude the discussion with diagnostic and treatment approaches to neurolisteriosis. In susceptible hosts, namely immunocompromised, pregnant, neonatal, or elderly patients, Listeria infection may result in CNS invasion, causing meningoencephalitis and, rarely, ventriculitis and rhombencephalitis. Although neurolisteriosis most commonly affects individuals with known risk factors, CNS infection is nevertheless possible in otherwise healthy young patients. Suspicion should be raised in patients with an exposure history who do not improve with empiric antibiotics.

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.

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.

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.

Use of Clustering to Investigate Changes in Intracranial Pressure Waveform Morphology in Patients with Ventriculitis.

OBJECTIVE: This study aimed to examine whether changes in intracranial pressure (ICP) waveform morphologies can be used as a biomarker for early detection of ventriculitis. METHODS: Consecutive patients (N = 1653) were prospectively enrolled in a hemorrhage outcomes study from 2006 to 2018. Of these, 435 patients (26%) required external ventricular drains (EVDs) and 76 (17.5% of those with EVDs) had ventriculitis treated with antibiotics. Nineteen patients (25% of those with ventriculitis) showed culture-positive cerebrospinal fluid (CSF) and were included in the present analysis. CSF was routinely cultured three times per week and additionally if infection was suspected. EVDs were left open for drainage, with ICP assessed hourly by clamping. Using wavelet analysis, we extracted uninterrupted segments of ICP waveforms. We extracted dominant pulses from continuous high-resolution data, using morphological clustering analysis of intracranial pressure (MOCAIP). Then we applied k-means clustering, using the dynamic time warping distance to obtain morphologically similar groupings. Finally, metaclusters and further-split clusters (when equipoise existed) were categorized for broad comparison by clinician consensus. RESULTS: We extracted 275,911 dominant pulses from 459.9 h of EVD data. Of these, 112,898 pulses (40.9%) occurred before culture positivity, 41,300 pulses (15.0%) occurred during culture positivity, and 121,713 pulses (44.1%) occurred after it. K-means identified 20 clusters, which were further grouped into metaclusters: tri-/biphasic, single-peak, and artifactual waveforms. Prior to ventriculitis, 61.8% of dominant pulses were tri-/biphasic; this percentage reduced to 22.6% during ventriculitis and 28.4% after it (p < 0.0001). One day before the first positive cultures were collected, the distribution of metaclusters changed to include more single-peak and artifactual ICP waveforms (p < 0.0001). CONCLUSION: The distribution of ICP waveform morphology changes significantly prior to clinical diagnosis of ventriculitis and may be a potential biomarker.

Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies.

Introduction: Healthcare-associated ventriculitis and meningitis occur after neurosurgical procedures, is associated with an adverse outcome in the majority of patients and represent a diagnostic challenge to clinicians. As the cerebrospinal fluid (CSF) culture is the cornerstone of diagnosis, obtaining CSF studies prior to starting antibiotic therapy is key.Areas covered: This review will evaluate the incidence, risk factors, clinical presentation, diagnosis, empirical intravenous antibiotic therapy, adjunctive intrathecal therapy, microbiology, prognosis, and prevention of HCAVM. We highlight the challenges and limitations of the currently available diagnostic methods and definitions and explore novel technologies. Our review included the search for published literature until June 2020.Expert opinion: Despite available preventive measures, HCAVM continues to occur and to be independently associated with significant neurological morbidity and mortality in the majority of patients. The cornerstone of the diagnosis of HCAVM is a positive CSF culture but the microbiological yield is reduced to ~50% with prior antimicrobial therapy. Although the CSF profile is not affected by antibiotic therapy it has a fair diagnostic accuracy. Future research efforts should concentrate in identifying novel diagnostic tools such as polymerase chain reaction (PCR) or metagenomic sequencing.

High-mobility group box-1 protein as a novel biomarker to diagnose healthcare-associated ventriculitis and meningitis: a pilot study.

BACKGROUND: The diagnosis of healthcare-associated ventriculitis and meningitis (HAVM) is challenging in the ICU setting. Traditional cerebrospinal fluid (CSF) markers and clinical signs of infection fail to diagnose HAVM in the critically ill setting. We sought to determine the diagnostic accuracy of measuring levels of high-mobility group box 1 (HMGB1) protein in cerebrospinal fluid (CSF) for the diagnosis of HAVM. METHODS: In this prospective observational cohort study, we enrolled 29 patients with an implanted external ventricular drainage (EVD). We tested the accuracy of CSF-HMGB1 as a diagnostic test for HAVM when compared to standard CSF parameters. RESULTS: HAVM was diagnosed in 11/29 (37.9%) patients. These patients had significantly higher CSF-HMGB1 levels compared to patients without HAVM (median [IQR] 43.39 [83.51] ng/mL vs 6.46 ng/mL [10.94]; P<0.001). CSF-HMGB1 and CSF-glucose were independently related to HAVM, with OR's (95% CI) of 15.43 (15.37 to 15.48, P<0.0001) and 0.31 (0.30 to 0.32, P<0.0001), respectively. The AUC [CI] of CSF-HMGB1 to predict HAVM was 0.83 [0.72 to 0.94]. CONCLUSIONS: HMGB1 is an accurate marker of HAVM and it adds incremental diagnostic value when paired with CSF-glucose measurements. Future larger and multicenter studies should assess the incremental diagnostic value of HMGB1 data when used alongside other established CSF markers of infection, and the external validity of these preliminary results.

Transmastoid and Transtemporal Drainage of Petrous Apicitis with Otitis Media.

BACKGROUND: Petrous apicitis (PA) is a serious infection involving the apical portion of the petrous temporal bone. The classic triad of purulent otorrhea, ipsilateral abducens nerve palsy and retroorbital pain is rarely seen due to early detection and widespread use of antibiotics. Medical management is the primary treatment modality with surgery reserved for cases of recalcitrant petrous apex abscess. METHODS AND RESULTS: We presented a case of PA with previously untreated otitis media. After multidisciplinary evaluation, the patient was initially treated with intravenous antibiotics followed by drainage of the abscess using a combined transmastoid and middle cranial fossa (MCF) approach. The patient recovered well with no recurrence of the infection based on imaging and symptoms. DISCUSSION: While a variety of different surgical approaches can be used in treatment of PA, we recommend the MCF approach in cases where access to the anterior petrous apex may be challenging via transcanal or transmastoid approach.

Chryseobacterium arthrosphaerae ventriculitis: A case report.

INTRODUCTION: Chryseobacterium arthrosphaerae is a gram-negative bacteria, known for its intrinsic multidrug resistance, which can lead to treatment difficulties. PATIENT CONCERNS: A 56-year-old male had an indwelling external ventricular drainage catheter for 6 months and had been frequently treated with antibiotics for nosocomial infections. He showed cerebrospinal fluid pleocytosis and an abrupt fever during hospitalization. DIAGNOSIS: He was diagnosed as a ventriculitis caused by Chryseobacterium arthrosphaerae (C arthrosphaerae). INTERVENTION: Initially, we used ciprofloxacin as the backbone in combination with minocycline (and rifampin). However, fever and pleocytosis persisted, and improvement was slow. We then switched the minocycline and rifampin regiment to trimethoprim/sulfamethoxazole. Following this switch of antibiotics, the patient's pleocytosis rapidly improved, allowing the replacement of his external ventricular drainage catheters. C arthrospharae was no longer growing in cerebrospinal fluid and he was recovered from ventriculitis. OUTCOMES: The patient remains alive without any incidence of C arthrosphaerae recurrence. CONCLUSION: We propose trimethoprim/sulfamethoxazole alone or in combination with ciprofloxacin to be good candidates for the treatment of ventriculitis by C arthrosphaerae.

Neonatal ventriculitis: a case series and review of literature.

Ventriculitis after meningitis is a serious complication in the neonatal age group. The role of intraventricular antibiotics in treatment is controversial. We present five such cases which were refractory to conventional intravenous antibiotic therapy, had persistent features of ventriculitis and in whom raised intracranial pressure (ICP) necessitated insertion of an external ventricular drain (EVD). Three of the five infants required intraventricular antibiotics but also developed EVD-related complications. Early diagnosis of ventriculitis and treatment is necessary to avoid a fatal outcome. Intravenous antibiotics are the treatment of choice, but intraventricular therapy may be considered in refractory cases. As the incidence of EVD-associated ventriculitis is high, proper care of EVDs and their early removal is mandatory.

Cerebrospinal Fluid Collected by Lumbar Puncture Has a Higher Diagnostic Accuracy than Collected by Ventriculostomy.

BACKGROUND: Patients harboring an external ventricular drain (EVD) who develop signs of infection require screening for infection in the central nervous system (CNS). The cerebrospinal fluid (CSF) can be collected by the EVD or by lumbar puncture (LP). If only one sample is analyzed, the diagnosis might be dubious or false-negative. The objective of this study was to compare the diagnosis accuracy of CNS infection of CSF samples collected from EVD and LP. METHODS: We conducted a transversal study where data were prospectively collected from 2016 to 2019. Patients harboring EVD with signs of infection were submitted to the CSF analysis collected by LP and EVD. Diagnosis sensibility and results correlation were analyzed using the kappa index. RESULTS: The 141 samples from LP and 141 samples from EVD were collected from 108 patients. Among the 282 samples, a total of 77 had infection. Seventy CSF samples from LP fulfilled infection criteria. However, only 32 EVD samples demonstrated infection. Among the 70 cases of infection based on the LP sample, 25 CSF samples collected from the EVD were also suggestive of infection; but in 45 patients only the CSF samples from LP met infection criteria. Seven patients had diagnosis of infection only in the EVD sample. The kappa correlation index of the results obtained from LP and EVD was 0.260 and the McNemar χ2 test was <0.01. CONCLUSIONS: The CSF analysis exclusive from the EVD has a low sensibility and negative predictive value. CSF collected from LP has a sensibility 2.18 times higher than EVD.