A search for bacteria identified from cerebrospinal fluid shunt infections in previous surgical events.

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on aerobic and anaerobic media. The detection and identification of bacteria was done with high throughput DNA sequencing methods and mass spectrometry. The presence of bacteria was confirmed in 4 infection samples, of which 2 were after initial placement and 2 after revision surgery. Taxonomic identification was consistent with clinical microbiology laboratory results. Bacteria were not detected in any of the CSF samples collected at the time of the previous surgical events. While our findings do not provide direct evidence for long-term persistence of pathogens, they suggest the need for consideration of additional source material, such as biofilm and environmental swabs, and/or the use of more sensitive and specific analytical methods.

Caregiver Values and Preferences Related to Surgical Decision-making for Children with Medical Complexity.

OBJECTIVE: To uncover the values and preferences of the caregivers for children with medical complexity (CMC), using the test case of surgical treatment decision-making for pediatric neuromuscular scoliosis (NMS) that will inform the future development of a decision support tool in this population. STUDY DESIGN: We conducted a qualitative study of semi-structured interviews of English- and Spanish-speaking caregivers of children with NMS from two geographically distinct children's hospitals. We used purposive sampling of language and treatment options selected to capture diverse experiences. Analysis was based on grounded theory with synthesized caregiver values and preferences themes. RESULTS: From 47 participants, we completed 41 interviews (9 in Spanish). Caregivers had a mean age of 43.2 years, were mostly White (66%), and had children with a mean age of 15.6. 64% chose surgery. The following values and preferences were important to many caregivers: reducing scoliosis-related pain, minimizing mobility limitations to optimize socio-emotional quality of life, limiting the impact of comorbidities on overall quality of life, information provided by peer support, the uncertainty of outcomes due to underlying comorbidities, and the uncertainty related to the anticipated progression of their child's scoliosis curve. Caregivers experienced immense uncertainty related to treatment outcomes due to their child's comorbidities. CONCLUSIONS: Caregivers of CMC may benefit from decision support that includes both values clarification exercises to help caregivers identify what of the many possible values and preferences are important to them and novel methods to communicate uncertainty in the care of CMC.

Cerebrospinal Fluid Shunt Infections.

Cerebrospinal fluid (CSF) shunt infections are a particularly challenging clinical problem. This review article addresses epidemiology and microbiology of CSF shunt infections. Clinical care is reviewed in detail, including recent guidelines and systematic review articles. Finally, current research into prevention and treatment is highlighted, with a discussion on the mechanisms of infection.

Neurodevelopmental and Mental Health Conditions in Children With Medical Complexity.

BACKGROUND AND OBJECTIVES: Children with medical complexity (CMC) may be at a high risk of neurodevelopmental and mental health conditions given disease comorbidities and lived experiences. Little is known about the prevalence of these conditions at a population level. In this study, we estimated the prevalence of neurodevelopmental and mental health diagnoses in CMC relative to children without medical complexity and measured associations between these diagnoses in CMC and subsequent health care utilization and in-hospital mortality. METHODS: We applied the Child and Adolescent Mental Health Disorders Classification System to identify neurodevelopmental and mental health diagnoses using all-payer claims data from three states (2012-2017). Poisson regression was used to compare outcomes in CMC with neurodevelopmental and mental health diagnoses to CMC without these diagnoses, adjusting for sociodemographic and clinical characteristics. RESULTS: Among 85 581 CMC, 39 065 (45.6%) had ≥1 neurodevelopmental diagnoses, and 31 703 (37.0%) had ≥1 mental health diagnoses, reflecting adjusted relative risks of 3.46 (3.42-3.50) for neurodevelopmental diagnoses and 2.22 (2.19-2.24) for mental health diagnoses compared with children without medical complexity. CMC with both neurodevelopmental and mental health diagnoses had 3.00 (95% confidence interval [CI]: 2.98-3.01) times the number of ambulatory visits, 69% more emergency department visits (rate ratio = 1.69, 95% CI: 1.66-1.72), 58% greater risk of hospitalization (rate ratio = 1.58, 95% CI: 1.50-1.67), and 2.32 times (95% CI: 2.28-2.36) the number of hospital days than CMC without these diagnoses. CONCLUSIONS: Neurodevelopmental and mental health diagnoses are prevalent among CMC and associated with increased health care utilization across the continuum of care. These findings illustrate the importance of recognizing and treating neurodevelopmental and mental health conditions in this population.

Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.

Infection rates during eras of intrathecal antibiotic use followed by antibiotic-impregnated catheter use in prevention of cerebrospinal fluid shunt infection.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) implemented a perioperative infection prevention bundle for all CSF shunt surgeries in 2007 that included the relatively unproven technique of intrathecal instillation of the broad-spectrum antibiotics vancomycin and gentamicin into the shunt. In the meantime, the field debated the use of antibiotic-impregnated catheter (AIC) shunt tubing using clindamycin and rifampin, an increasingly widespread, but expensive and controversial, technique. It is unknown whether there were changes in infecting organisms associated with the use of these techniques during CSF shunt surgery at the hospital level. Key comparison periods include during the use of intrathecal antibiotics (period 1 from June 1, 2007, to December 31, 2011, at HCRN hospitals) and AIC (period 2 from January 1, 2012, to December 31, 2015, at HCRN as well as increasing over time at non-HCRN hospitals) and only standard use of routine prophylactic antibiotics (period 1 at non-HCRN hospitals). The aim of this study was to examine rates of CSF shunt surgery-related infections from 2007 to 2012 at the hospital level, including HCRN and non-HCRN hospitals, with a focus on infections with gram-negative organisms. METHODS: The authors conducted a retrospective observational cohort study at 6 children's hospitals with enrollment from 2007 to 2012 and surveillance through 2015. Bimonthly rates of shunt surgery-related infections were summarized to produce an overall hospital-specific time series, as well as by HCRN/non-HCRN status. An interrupted time series analysis was performed to assess the impact of change in HCRN perioperative infection prevention bundle on overall bimonthly infection rates. Quarterly rates of gram-negative shunt surgery-related infections were summarized to produce an overall hospital-specific time series. RESULTS: The overall bimonthly CSF shunt infection rate over time did not change significantly from 2007 to 2012. There was no difference in the trajectory of infection rates between HCRN and non-HCRN hospitals during the entire study period. No change in distributions of gram-negative organism infections was observed in hospitals from 2007 to 2015. CONCLUSIONS: There were no differences observed in hospital-level infection rates for low-risk patients undergoing CSF shunt surgery. This included analyses based on participation in the HCRN network, given their regular use of intrathecal antibiotics in period 1 and a focus on gram-negative infections with increasing adoption of AICs in period 2.

Factors associated with tracheostomy-associated infection treatment: A multicenter observational study.

OBJECTIVE: To characterize factors that influence the decision to treat suspected pediatric bacterial tracheostomy-associated respiratory infections (bTRAINs; e.g., pneumonia, tracheitis). METHODS: We conducted a multicenter, prospective cohort study of children with pre-existing tracheostomy hospitalized at six children's hospitals for a suspected bTRAIN (receipt of respiratory culture plus ≥1 doses of an antibiotic within 48 h). The primary predictor was respiratory culture growth categorized as Pseudomonas aeruginosa, P. aeruginosa + ≥1 other bacterium, other bacteria alone, or normal flora/no growth. Our primary outcome was bTRAIN treatment with a complete course of antibiotics as documented by the discharge team. We used logistic regression with generalized estimating equations to identify the association between our primary predictor and outcome and to identify demographic, clinical, and diagnostic testing factors associated with treatment. RESULTS: Of the 440 admissions among 289 patients meeting inclusion criteria, 307 (69.8%) had positive respiratory culture growth. Overall, 237 (53.9%) of admissions resulted in bTRAIN treatment. Relative to a negative culture, a culture positive for P. aeruginosa plus ≥1 other organism (adjusted odds ratio [aOR] 2.3; 95% confidence interval [CI] 1.02-5.0)] or ≥1 other organism alone (aOR: 2.8; 95% CI: 1.4-5.6)] was associated with treatment. Several clinical and diagnostic testing (respiratory Gram-stain and chest radiograph) findings were also associated with treatment. Positive respiratory viral testing was associated with reduced odds of treatment (aOR: 0.5; 95% CI: 0.2-0.9). CONCLUSIONS: Positive respiratory cultures as well as clinical indicators of acute illness and nonculture test results were associated with bTRAIN treatment. Clinicians may be more comfortable withholding antibiotics when a virus is identified during testing.

Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery.

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

National Characteristics of Emergency Care for Children with Neurologic Complex Chronic Conditions.

Introduction: Most pediatric emergency care occurs in general emergency departments (GED), where less pediatric experience and lower pediatric emergency readiness may compromise care. Medically vulnerable pediatric patients, such as those with chronic, severe, neurologic conditions, are likely to be disproportionately affected by suboptimal care in GEDs; however, little is known about characteristics of their care in either the general or pediatric emergency setting. In this study our objective was to compare the frequency, characteristics, and outcomes of ED visits made by children with chronic neurologic diseases between general and pediatric EDs (PED). Methods: We conducted a retrospective analysis of the 2011-2014 Nationwide Emergency Department Sample (NEDS) for ED visits made by patients 0-21 years with neurologic complex chronic conditions (neuro CCC). We compared patient, hospital, and ED visits characteristics between GEDs and PEDs using descriptive statistics. We assessed outcomes of admission, transfer, critical procedure performance, and mortality using multivariable logistic regression. Results: There were 387,813 neuro CCC ED visits (0.3% of 0-21-year-old ED visits) in our sample. Care occurred predominantly in GEDs, and visits were associated with a high severity of illness (30.1% highest severity classification score). Compared to GED visits, PED neuro CCC visits were comprised of individuals who were younger, more likely to have comorbid conditions (32.9% vs 21%, P < 0.001), and technology assistance (65.4% vs. 45.9%) but underwent fewer procedures and had lower ED charges ($2,200 vs $1,520, P < 0.001). Visits to PEDs had lower adjusted odds of critical procedures (adjusted odds ratio [aOR] 0.74, 95% confidence interval [CI] 0.62-0.87), transfers (aOR 0.14, 95% CI 0.04-0.56), and mortality (aOR 0.38, 95% CI 0.19-0.75) compared to GEDs. Conclusion: Care for children with neuro CCCs in a pediatric ED is associated with less resource utilization and lower rates of transfer and mortality. Identifying features of PED care for neuro CCCs could lead to lower costs and mortality for this population.

Utilization trends in cerebrospinal fluid shunt infection prevention techniques in the United States from 2007 to 2015.

OBJECTIVE: The objective of this study was to describe trends in the utilization of infection prevention techniques (standard care, intrathecal [IT] antibiotics, antibiotic-impregnated catheters [AICs], and combination of IT antibiotics and AICs) among participating hospitals over time. METHODS: This retrospective cohort study at six large children's hospitals between 2007 and 2015 included children ≤ 18 years of age who underwent initial shunt placement between 2007 and 2012. Pediatric Health Information System + (PHIS+) data were augmented with chart review data for all shunt surgeries that occurred prior to the first shunt infection. The Pearson chi-square test was used to test for differences in outcomes. RESULTS: In total, 1723 eligible children had initial shunt placement between 2007 and 2012, with 3094 shunt surgeries through 2015. Differences were noted between hospitals in gestational age, etiology of hydrocephalus, and race and ethnicity, but not sex, weight at surgery, and previous surgeries. Utilization of infection prevention techniques varied across participating hospitals. Hydrocephalus Clinical Research Network hospitals used more IT antibiotics in 2007-2011; after 2012, increasing adoption of AICs was observed in most hospitals. CONCLUSIONS: A consistent trend of decreasing IT antibiotic use and increased AIC utilization was observed after 2012, except for hospital B, which consistently used AICs.

Associations of Standard Care, Intrathecal Antibiotics, and Antibiotic-Impregnated Catheters With Cerebrospinal Fluid Shunt Infection Organisms and Resistance.

BACKGROUND: Infection prevention techniques used during cerebrospinal fluid (CSF) shunt surgery include: (1) standard perioperative intravenous antibiotics, (2) intrathecal (IT) antibiotics, (3) antibiotic-impregnated catheter (AIC) shunt tubing, or (4) Both IT and AIC. These techniques have not been assessed against one another for their impact on the infecting organisms and patterns of antimicrobial resistance. METHODS: We performed a retrospective longitudinal observational cohort study of children with initial CSF shunt placement between January 2007 and December 2012 at 6 US hospitals. Data were collected electronically from the Pediatric Health Information Systems+ (PHIS+) database, and augmented with standardized chart review. Only subjects with positive CSF cultures were included in this study. RESULTS: Of 1,723 children whose initial shunt placement occurred during the study period, 196 (11%) developed infection, with 157 (80%) having positive CSF cultures. Of these 157 subjects, 69 (44%) received standard care, 28 (18%) received AIC, 55 (35%) received IT antibiotics, and 5 (3%) received Both at the preceding surgery. The most common organisms involved in monomicrobial infections were Staphylococcus aureus (38, 24%), coagulase-negative staphylococci (36, 23%), and Cutibacterium acnes (6, 4%). Compared with standard care, the other infection prevention techniques were not significantly associated with changes to infecting organisms; AIC was associated with decreased odds of methicillin resistance among coagulase-negative staphylococci. CONCLUSIONS: Because no association was found between infection prevention technique and infecting organisms when compared to standard care, other considerations such as tolerability, availability, and cost should inform decisions about infection prevention during CSF shunt placement surgery.

Lower levels of Th1 and Th2 cytokines in cerebrospinal fluid (CSF) at the time of initial CSF shunt placement in children are associated with subsequent shunt revision surgeries.

OBJECTIVE: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries. METHODS: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt revision surgeries during >=24 months of follow-up (n = 7); as well as children who underwent an initial CSF shunt placement and then required repeated CSF shunt revision surgeries (n = 3). Levels of 92 human cytokines were measured using the Olink immunoassay and 41 human cytokines were measured using Luminex based bead array on CSF obtained at the time of each child's initial CSF shunt placement and were displayed in heat maps. RESULTS: Qualitatively similar profiles for the majority of cytokines were observed among the patients in each group in both Olink and Luminex assays. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Pro- and anti-inflammatory cytokines were selected a priori and shown across subsequent revision surgeries for the 3 patients. Cytokine patterns differed between patients, but within a given patient pro-inflammatory and anti-inflammatory cytokines acted in a parallel fashion, with the exception of IL-4. CONCLUSIONS: Heat maps of cytokine levels at the time of initial CSF shunt placement for each child undergoing only a single initial CSF shunt placement and for each child undergoing repeat CSF shunt revision surgeries demonstrated qualitatively similar profiles for the majority of cytokines. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Better stratification by patient age, etiology, and mechanism of failure is needed to develop a deeper understanding of the mechanism of inflammation in the development of hydrocephalus and response to shunting in children.

Comparison of outcomes in the management of abdominal pseudocyst in children with shunted hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: Abdominal pseudocyst (APC) can cause distal site failure in children with ventriculoperitoneal shunts and is specifically designated as an infection in Hydrocephalus Clinical Research Network (HCRN) protocols. Specific management and outcomes of children with APCs have not been reported in a multicenter study. In this study, the authors investigated the management and outcomes of APC in children with shunted hydrocephalus who were treated at centers in the HCRN. METHODS: The HCRN Registry was queried to identify children < 18 years old with shunts who were diagnosed with an APC (i.e., a loculated abdominal fluid collection containing the peritoneal catheter with abdominal distention and/or displacement of peritoneal contents). The primary outcome was shunt failure after APC treatment. The primary variable was reimplantation of the distal catheter after pseudocyst treatment back into the peritoneum versus implantation in a nonperitoneal site. Other risk factors for shunt failure after APC treatment and variability in APC management were investigated. RESULTS: Among 141 children from 14 centers who underwent first-time management of an APC over a 14-year period, the median time from previous shunt surgery to APC diagnosis was 3.8 months. Overall, 17.7% of children had a positive culture: APC cultures were positive in 14.2% and CSF cultures in 15.6%. Six other children underwent shunt revision without removal; all underwent reoperation within 1 month. There was no difference in shunt survival (log-rank test, p = 0.42) or number of subsequent revisions within 6, 12, or 24 months for shunts reimplanted in the abdomen versus those implanted in a nonperitoneal location. Nonperitoneal implantation was associated with more noninfectious revisions (42.3% vs 22.9%, p = 0.019), whereas infection was more common after reimplantation in the abdomen (25.7% vs 7.0%, p = 0.003). Univariable analysis demonstrated that younger age at APC diagnosis (8.3 vs 12.2 years, p = 0.006) and prior shunt procedure within 12 weeks of APC diagnosis (59.5% vs 40.5%, p = 0.012) were associated with shunt failure after APC treatment. Multivariable modeling confirmed that prior shunt surgery within 12 weeks of APC diagnosis was independently associated with failure (HR 1.79 [95% CI 1.04-3.07], p = 0.035). CONCLUSIONS: In the HCRN, APCs in the setting of CSF shunts are usually managed with externalization. Shunt surgery within 12 weeks of APC diagnosis was associated with risk of failure after APC treatment. Although no differences were found in overall shunt failure rate, noninfectious shunt revisions were more common in the nonperitoneal distal catheter sites, and infection was a more common reason for failure after reimplantation of the shunt in the abdomen.

Characterization of cerebrospinal fluid (CSF) microbiota at the time of initial surgical intervention for children with hydrocephalus.

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention. STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in STGG or standard clinical) were further analyzed using whole-genome amplification sequencing (WGAS). RESULTS: 11/66 (17%) samples stored in STGG and 1/36 (3%) that underwent standard clinical microbiological culture demonstrated bacterial growth. Of the organisms present, 8 were common skin flora and 4 were potential pathogens; only 1 was also qPCR positive. WGAS findings and STGG culture findings were concordant for only 1 sample, identifying Staphylococcus epidermidis. No significant difference in time to second surgical intervention was observed between the STGG culture-positive and negative groups. CONCLUSION(S): Using high sensitivity methods, we detected the presence of bacteria in a subset of CSF samples at the time of first surgery. Therefore, the true presence of bacteria in CSF of children with hydrocephalus cannot be ruled out, though our findings may suggest these bacteria are contaminants or false positives of the detection methods. Regardless of origin, the detection of microbiota in the CSF of these children may not have any clinical significance.

A Refined, Controlled 16S rRNA Gene Sequencing Approach Reveals Limited Detection of Cerebrospinal Fluid Microbiota in Children with Bacterial Meningitis.

Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads, such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples with low bacterial loads by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures. Several bench and computational approaches were taken to address potential sources of error for low bacterial load samples. We compared DNA yields and sequencing results after applying three different DNA extraction approaches to an artificially constructed mock-bacterial community. We also compared two postsequencing computational contaminant removal strategies, decontam R and full contaminant sequence removal. All three extraction techniques followed by decontam R yielded similar results for the mock community. We then applied these methods to 22 CSF samples from children diagnosed with meningitis, which has low bacterial loads relative to other clinical infection samples. The refined 16S HTS pipelines identified the cultured bacterial genus as the dominant organism for only 3 of these samples. We found that all three DNA extraction techniques followed by decontam R generated similar DNA yields for mock communities at the low bacterial loads representative of CSF samples. However, the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches, despite rigorous controls and sophisticated computational approaches. Although we did not find current DNA-based diagnostics to be useful for pediatric meningitis samples, the utility of these methods for CSF shunt infection remains undefined. Future advances in sample processing methods to minimize or eliminate contamination will be required to improve the sensitivity and specificity of these methods for pediatric meningitis. IMPORTANCE Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. These refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures. We found that the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches, despite rigorous controls and sophisticated computational approaches.

Endoscopic third ventriculostomy in previously shunt-treated patients.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) is an option for treatment of hydrocephalus, including for patients who have a history of previous treatment with CSF shunt insertion. The purpose of this study was to report the success of postshunt ETV by using data from a multicenter prospective registry. METHODS: Prospectively collected data in the Hydrocephalus Clinical Research Network (HCRN) Core Data Project (i.e., HCRN Registry) were reviewed. Children who underwent ETV between 2008 and 2019 and had a history of previous treatment with a CSF shunt were included. A Kaplan-Meier survival curve was created for the primary outcome: time from postshunt ETV to subsequent CSF shunt placement or revision. Univariable Cox proportional hazards models were created to evaluate for an association between clinical and demographic variables and subsequent shunt surgery. Postshunt ETV complications were also identified and categorized. RESULTS: A total of 203 children were included: 57% male and 43% female; 74% White, 23% Black, and 4% other race. The most common hydrocephalus etiologies were postintraventricular hemorrhage secondary to prematurity (56, 28%) and aqueductal stenosis (42, 21%). The ETV Success Score ranged from 10 to 80. The median patient age was 4.1 years. The overall success of postshunt ETV at 6 months was 41%. Only the surgeon's report of a clear view of the basilar artery was associated with a lower likelihood of postshunt ETV failure (HR 0.43, 95% CI 0.23-0.82, p = 0.009). None of the following variables were associated with postshunt ETV success: age at the time of postshunt ETV, etiology of hydrocephalus, sex, race, ventricle size, number of previous shunt operations, ETV performed at time of shunt infection, and use of external ventricular drainage. Overall, complications were reported in 22% of patients, with CSF leak (8.6%) being the most common complication. CONCLUSIONS: Postshunt ETV was successful in treating hydrocephalus, without subsequent need for a CSF shunt, in 41% of patients, with a clear view of the basilar artery being the only variable significantly associated with success. Complications occurred in 22% of patients. ETV is an option for treatment of hydrocephalus in children who have previously undergone shunt placement, but with a lower than expected likelihood of success.

Prevalence of Children With Medical Complexity and Associations With Health Care Utilization and In-Hospital Mortality.

Importance: Children with medical complexity (CMC) have substantial health care needs and frequently experience poor health care quality. Understanding the population prevalence and associated health care needs can inform clinical and public health initiatives. Objective: To estimate the prevalence of CMC using open-source pediatric algorithms, evaluate performance of these algorithms in predicting health care utilization and in-hospital mortality, and identify associations between medical complexity as defined by these algorithms and clinical outcomes. Design, Setting, and Participants: This retrospective cohort study used all-payer claims data from Colorado, Massachusetts, and New Hampshire from 2012 through 2017. Children and adolescents younger than 18 years residing in these states were included if they had 12 months or longer of enrollment in a participating health care plan. Analyses were conducted from March 12, 2021, to January 7, 2022. Exposures: The pediatric Complex Chronic Condition Classification System, Pediatric Medical Complexity Algorithm, and Children With Disabilities Algorithm were applied to 3 years of data to identify children with complex and disabling conditions, first in their original form and then using more conservative criteria that required multiple health care claims or involvement of 3 or more body systems. Main Outcomes and Measures: Primary outcomes, examined over 2 years, included in-hospital mortality and a composite measure of health care services, including specialized therapies, specialized medical equipment, and inpatient care. Outcomes were modeled using logistic regression. Model performance was evaluated using C statistics, sensitivity, and specificity. Results: Of 1 936 957 children, 48.4% were female, 87.8% resided in urban core areas, and 45.1% had government-sponsored insurance as their only primary payer. Depending on the algorithm and coding criteria applied, 0.67% to 11.44% were identified as CMC. All 3 algorithms had adequate discriminative ability, sensitivity, and specificity to predict in-hospital mortality and composite health care services (C statistic = 0.76 [95% CI, 0.73-0.80] to 0.81 [95% CI, 0.78-0.84] for mortality and 0.77 [95% CI, 0.76-0.77] to 0.80 [95% CI, 0.79-0.80] for composite health care services). Across algorithms, CMC had significantly greater odds of mortality (adjusted odds ratio [aOR], 9.97; 95% CI, 7.70-12.89; to aOR, 69.35; 95% CI, 52.52-91.57) and composite health care services (aOR, 4.59; 95% CI, 4.44-4.73; to aOR, 18.87; 95% CI, 17.87-19.93) than children not identified as CMC. Conclusions and Relevance: In this study, open-source algorithms identified different cohorts of CMC in terms of prevalence and magnitude of risk, but all predicted increased health care utilization and in-hospital mortality. These results can inform research, programs, and policies for CMC.

Endoscopic third ventriculostomy revision after failure of initial endoscopic third ventriculostomy and choroid plexus cauterization.

OBJECTIVE: Primary treatment of hydrocephalus with endoscopic third ventriculostomy (ETV) and choroid plexus cauterization (CPC) is well described in the neurosurgical literature, with wide reported ranges of success and complication rates. The purpose of this study was to describe the safety and efficacy of ETV revision after initial ETV+CPC failure. METHODS: Prospectively collected data in the Hydrocephalus Clinical Research Network Core Data Project registry were reviewed. Children who underwent ETV+CPC as the initial treatment for hydrocephalus between 2013 and 2019 and in whom the initial ETV+CPC was completed (i.e., not abandoned) were included. Log-rank survival analysis (the primary analysis) was used to compare time to failure (defined as any other surgical treatment for hydrocephalus or death related to hydrocephalus) of initial ETV+CPC versus that of ETV revision by using random-effects modeling to account for the inclusion of patients in both the initial and revision groups. Secondary analysis compared ETV revision to shunt placement after failure of initial ETV+CPC by using the log-rank test, as well as shunt failure after ETV+CPC to that after ETV revision. Cox regression analysis was used to identify predictors of failure among children treated with ETV revision. RESULTS: The authors identified 521 ETV+CPC procedures that met their inclusion criteria. Ninety-one children underwent ETV revision after ETV+CPC failure. ETV revision had a lower 1-year success rate than initial ETV+CPC (29.5% vs 45%, p < 0.001). ETV revision after initial ETV+CPC failure had a lower success rate than shunting (29.5% vs 77.8%, p < 0.001). Shunt survival after initial ETV+CPC failure was not significantly different from shunt survival after ETV revision failure (p = 0.963). Complication rates were similar for all examined surgical procedures (initial ETV+CPC, ETV revision, ventriculoperitoneal shunt [VPS] placement after ETV+CPC, and VPS placement after ETV revision). Only young age was predictive of ETV revision failure (p = 0.02). CONCLUSIONS: ETV revision had a significantly lower 1-year success rate than initial ETV+CPC and VPS placement after ETV+CPC. Complication rates were similar for all studied procedures. Younger age, but not time since initial ETV+CPC, was a risk factor for ETV revision failure.