How do we change practice?

OBJECT: The goal of this video lecture was to show the importance to research group organizing protocols to reduce cerebrospinal fluid (CSF) shunt infection at Hydrocephalus Clinical Research Network (HCRN) centers (from 8.7% to 5.7%). Antibiotic-impregnated catheters (AICs) were not part of the protocol but were used off protocol by some surgeons. The authors therefore began using a new protocol that included AICs in an effort to reduce the infection rate further. The improvement of quality was related to reduce variation and improve outcome. METHODS The previous protocol was implemented at HCRN centers on January 1, 2012, for all shunt procedures (excluding external ventricular drains [EVDs], ventricular reservoirs, and subgaleal shunts). Compliance with the protocol and outcome events up to March 30, 2014, were recorded. The actual protocol is based on 7 points (HCRNq centers): intravenous antibiotics, skin preparation, hand scrub, double gloves, iodophoretic surgical field, catheter and antibiotics, and vancomycin irrigation RESULTS. Before protocol implementation in 30 participating centers, and 1318 subjects (1571 surgical cases) enrolled the overall infection rate was 6.0% (95% CI 5.1%-7.2%). The actual infection rate when using this new protocol has been analyzed. CONCLUSIONS CSF shunt procedures performed in compliance with a new infection prevention protocol at HCRNq centers had a lower infection rate than noncompliant procedures. Based on the current data, HCRNq centers the role of AICs compared with other infection prevention measures is still under analysis.

Brucella Shunt Infection Complicated by Peritonitis: Case Report and Review of the Literature

Brucellosis is an endemic zoonotic disease in the Mediterranean basin and Middle East. The disease remains a diagnostic challenge due to an increasing trend of ambiguous and non-specific manifestations. We report a rare case of a 9-year-old boy who had a left frontotemporal arachnoid cyst with cystoperitoneal shunt who presented with fever for 2 weeks with gastrointestinal symptoms. He had no neurological manifestations. Diagnosis of Brucella shunt infection complicated with a peritoneal collection was established by isolation of the organism from cerebrospinal fluid (CSF) culture. Successful treatment was accomplished by shunt replacement and intravenous antibiotics followed by step-down oral therapy for an 18-month duration based on serological and radiological responses with no sequelae. We also reviewed the reported cases of CSF shunt infection in the literature for further guidance. Brucella shunt infection may be difficult to diagnose due to the diversity of signs and symptoms and the low yield on culture. Brucellosis should be always kept in mind in the differential diagnosis of patients living in endemic area with fever and non-specific symptoms. Diagnosis depends on a high index of suspicion. In addition to drug therapy, device replacement is advised to prevent treatment failure.

Characterization of cerebrospinal fluid (CSF) microbiota from patients with CSF shunt infection and reinfection using high throughput sequencing of 16S ribosomal RNAgenes

Background Nearly 20% of patients with cerebrospinal fluid (CSF) shunt infection develop reinfection. It is unclear whether reinfections are caused by an organism previously present or are independent infection events. Objective We used bacterial culture and high throughput sequencing (HTS) of 16S ribosomal RNA (rRNA) genes to identify bacteria present in serial CSF samples obtained from children who failed CSF shunt infection treatment. We hypothesized that organisms that persist in CSF despite treatment would be detected upon reinfection. Design/methods Serial CSF samples were obtained from 6 patients, 5 with 2 infections and 1 with 3 infections; the study was limited to those for which CSF samples were available from the end of infection and beginning of reinfection. Amplicons of the 16S rRNA gene V4 region were sequenced. Taxonomic assignments of V4 sequences were compared with bacterial species identified in culture. Results Seven infection dyads averaging 13.5 samples per infection were analyzed. A median of 8 taxa [interquartile range (IQR) 5–10] were observed in the first samples from reinfection using HTS. Conventional culture correlated with high abundance of an organism by HTS in all but 1 infection. In 6 of 7 infection dyads, organisms identified by culture at reinfection were detected by HTS of culture-negative samples at the end of the previous infection. The median Chao-Jaccard abundance-based similarity index for matched infection pairs at end of infection and beginning of reinfection was 0.57 (IQR 0.07–0.87) compared to that for unmatched pairs of 0.40 (IQR 0.10–0.60) [p = 0.46]. Conclusion(s) HTS results were generally consistent with culture-based methods in CSF shunt infection and reinfection, and may detect organisms missed by culture at the end of infection treatment but detected by culture at reinfection. However, the CSF microbiota did not correlate more closely within patients at the end of infection and beginning of reinfection than between any two unrelated infections. We cannot reject the hypothesis that sequential infections were independent.

C. acnes central nervous system catheter infection induces long-term changes in the CSF proteome

Cutibacterium acnes (C. acnes) is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is likely underdiagnosed due to the difficulty in culturing this pathogen. Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. Currently the gold standard for identifying CSF shunt infections is microbiologic culture. However, C. acnes infection often results in falsely negative cultures; therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a rat model of CSF catheter infection to C. acnes. We found elevated levels of IL-1β, IL-6, CCL2 and IL-10 in the CSF and brain tissues of animals implanted with C. acnes-infected catheters compared to sterile controls at day 1 post-infection. This coincided with modest increases in neutrophils in the CSF and to a greater extent the brain tissue of animals with C. acnes infection, which closely mirrors the clinical findings in patients with C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of disease, typified at day 1 post-infection by an acute phase and pathogen neutralization response evolving to a response consistent with wound resolution at day 28, compared to sterile catheter placement. Collectively, these results demonstrate that it is possible to distinguish C. acnes infection from sterile post-operative inflammation and CSF proteins could be useful in a diagnostic strategy for this pathogen that is difficult to diagnose.

Pediatric Neurosurgery

This chapter focuses on pediatric neurosurgery. The first study compares the results of extended strip craniectomy versus subtotal calvarectomy with cranial vault remodeling for patients with sagittal craniosynostosis, while the second study tests the safety and efficacy of minimally invasive endoscopic strip craniectomy followed by helmet molding therapy in the treatment of infantile craniosynostosis. The next three studies determine the success of endoscopic third ventriculostomy (ETV) in the treatment of childhood hydrocephalus, evaluate the risk factors for cerebrospinal fluid (CSF) shunt infection following initial shunt replacement, and assess the efficacy of drainage, irrigation, and fibrinolytic therapy (DRIFT) for premature infants with posthemorrhagic ventricular dilatation. Meanwhile, the following set of studies identifies the genetic alterations related to the pathogenesis of pediatric medulloblastoma and discusses the effect of prolonged postoperative chemotherapy on the ability to delay the delivery of radiation in children younger than 3 years of age with malignant brain tumors. The following two studies investigate whether prenatal repair of myelomeningocele could result in better neurologic function compared with the standard postnatal repair and explore functional outcomes following selective posterior rhizotomy in children with cerebral palsy. The last study is of historical value and explore Cushing’s critical review of cerebellar medulloblastomas.

Relationship of causative organism and time to infection among children with cerebrospinal fluid shunt infection

OBJECTIVEInfection is a common complication of cerebrospinal fluid (CSF) shunts, occurring in 6%–20% of children. Although studies are limited, Staphylococcus aureus is thought to cause more rapid and aggressive infection than coagulase-negative Staphylococcus (CONS) or gram-negative organisms. The authors’ objective was to evaluate the relationship between the causative organisms of CSF shunt infection and the timing of infection.METHODSThe authors performed a retrospective cohort study of children who underwent CSF shunt placement at a tertiary care children’s hospital over a 9-year period and subsequently developed a CSF shunt infection. The primary predictor variable was the causative organism recovered from CSF culture, characterized as S. aureus, CONS, or gram-negative organisms. The primary outcome was time to infection, defined as the number of days from most recent shunt intervention to the diagnosis of the infection. The association between causative organism and time to infection was visualized using Kaplan-Meier curves, and statistical comparisons were made using nonparametric Kruskal-Wallis tests.RESULTSAmong 103 children in whom a CSF shunt infection developed, the causative organism was CONS in 57 (55%), S. aureus in 19 (18%), and gram-negative organisms in 9 (9%). The median time to infection did not differ (p = 0.81) for infections caused by CONS (20 days, IQR 11–40), S. aureus (26 days, IQR 12–95), and gram-negative organisms (23 days, IQR 17–34).CONCLUSIONSNo significant difference in time to infection based on the causative organism was observed among children with a CSF shunt infection.

Reinfection rates following adherence to Infectious Diseases Society of America guideline recommendations in first cerebrospinal fluid shunt infection treatment

OBJECTIVECSF shunt infection treatment requires both surgical and antibiotic decisions. Using the Hydrocephalus Clinical Research Network (HCRN) Registry and 2004 Infectious Diseases Society of America (IDSA) guidelines that were not proactively distributed to HCRN providers, the authors previously found high adherence to surgical recommendations but poor adherence to intravenous (IV) antibiotic duration recommendations. In general, IV antibiotic duration was longer than recommended. In March 2017, new IDSA guidelines expanded upon the 2004 guidelines by including recommendations for selection of specific antibiotics. The objective of this study was to describe adherence to both 2004 and 2017 IDSA guideline recommendations for CSF shunt infection treatment, and to report reinfection rates associated with adherence to guideline recommendations.METHODSThe authors investigated a prospective cohort of children younger than 18 years of age who underwent treatment for first CSF shunt infection at one of 7 hospitals from April 2008 to December 2012. CSF shunt infection was diagnosed by recovery of bacteria from CSF culture (CSF-positive infection). Adherence to 2004 and 2017 guideline recommendations was determined. Adherence to antibiotics was further classified as longer or shorter duration than guideline recommendations. Reinfection rates with 95% confidence intervals (CIs) were generated.RESULTSThere were 133 children with CSF-positive infections addressed by 2004 IDSA guideline recommendations, with 124 at risk for reinfection. Zero reinfections were observed among those whose treatment was fully adherent (0/14, 0% [95% CI 0%–20%]), and 15 reinfections were observed among those whose infection treatment was nonadherent (15/110, 14% [95% CI 8%–21%]). Among the 110 first infections whose infection treatment was nonadherent, 74 first infections were treated for a longer duration than guidelines recommended and 9 developed reinfection (9/74, 12% [95% CI 6%–22%]). There were 145 children with CSF-positive infections addressed by 2017 IDSA guideline recommendations, with 135 at risk for reinfection. No reinfections were observed among children whose treatment was fully adherent (0/3, 0% [95% CI 0%–64%]), and 18 reinfections were observed among those whose infection treatment was nonadherent (18/132, 14% [95% CI 8%–21%]).CONCLUSIONSThere is no clear evidence that either adherence to IDSA guidelines or duration of treatment longer than recommended is associated with reduction in reinfection rates. Because IDSA guidelines recommend shorter IV antibiotic durations than are typically used, improvement efforts to reduce IV antibiotic use in CSF shunt infection treatment can and should utilize IDSA guidelines.

Patient and Treatment Characteristics by Infecting Organism in Cerebrospinal Fluid Shunt Infection

Background Previous studies of cerebrospinal fluid (CSF) shunt infection treatment have been limited in size and unable to compare patient and treatment characteristics by infecting organism. Our objective was to describe variation in patient and treatment characteristics for children with first CSF shunt infection, stratified by infecting organism subgroups outlined in the 2017 Infectious Disease Society of America’s (IDSA) guidelines. Methods We studied a prospective cohort of children <18 years of age undergoing treatment for first CSF shunt infection at one of 7 Hydrocephalus Clinical Research Network hospitals from April 2008 to December 2012. Differences between infecting organism subgroups were described using univariate analyses and Fisher’s exact tests. Results There were 145 children whose infections were diagnosed by CSF culture and addressed by IDSA guidelines, including 47 with Staphylococcus aureus, 52 with coagulase-negative Staphylococcus, 37 with Gram-negative bacilli, and 9 with Propionibacterium acnes. No differences in many patient and treatment characteristics were seen between infecting organism subgroups, including age at initial shunt, gender, race, insurance, indication for shunt, gastrostomy, tracheostomy, ultrasound, and/or endoscope use at all surgeries before infection, or numbers of revisions before infection. A larger proportion of infections were caused by Gram-negative bacilli when antibiotic-impregnated catheters were used at initial shunt placement (12 of 23, 52%) and/or subsequent revisions (11 of 23, 48%) compared with all other infections (9 of 68 [13%] and 13 of 68 [19%], respectively). No differences in reinfection were observed between infecting organism subgroups. Conclusions The organism profile encountered at infection differs when antibiotic-impregnated catheters are used, with a higher proportion of Gram-negative bacilli. This warrants further investigation given increasing adoption of antibiotic-impregnated catheters.

Reinfection after treatment of first cerebrospinal fluid shunt infection: a prospective observational cohort study

OBJECTIVECSF shunt infection requires both surgical and antibiotic treatment. Surgical treatment includes either total shunt removal with external ventricular drain (EVD) placement followed by new shunt insertion, or distal shunt externalization followed by new shunt insertion once the CSF is sterile. Antibiotic treatment includes the administration of intravenous antibiotics. The Hydrocephalus Clinical Research Network (HCRN) registry provides a unique opportunity to understand reinfection following treatment for CSF shunt infection. This study examines the association of surgical and antibiotic decisions in the treatment of first CSF shunt infection with reinfection.METHODSA prospective cohort study of children undergoing treatment for first CSF infection at 7 HCRN hospitals from April 2008 to December 2012 was performed. The HCRN consensus definition was used to define CSF shunt infection and reinfection. The key surgical predictor variable was surgical approach to treatment for CSF shunt infection, and the key antibiotic treatment predictor variable was intravenous antibiotic selection and duration. Cox proportional hazards models were constructed to address the time-varying nature of the characteristics associated with shunt surgeries.RESULTSOf 233 children in the HCRN registry with an initial CSF shunt infection during the study period, 38 patients (16%) developed reinfection over a median time of 44 days (interquartile range [IQR] 19–437). The majority of initial CSF shunt infections were treated with total shunt removal and EVD placement (175 patients; 75%). The median time between infection surgeries was 15 days (IQR 10–22). For the subset of 172 infections diagnosed by CSF culture, the mean ± SD duration of antibiotic treatment was 18.7 ± 12.8 days. In all Cox proportional hazards models, neither surgical approach to infection treatment nor overall intravenous antibiotic duration was independently associated with reinfection. The only treatment decision independently associated with decreased infection risk was the use of rifampin. While this finding did not achieve statistical significance, in all 5 Cox proportional hazards models both surgical approach (other than total shunt removal at initial CSF shunt infection) and nonventriculoperitoneal shunt location were consistently associated with a higher hazard of reinfection, while the use of ultrasound was consistently associated with a lower hazard of reinfection.CONCLUSIONSNeither surgical approach to treatment nor antibiotic duration was associated with reinfection risk. While these findings did not achieve statistical significance, surgical approach other than total removal at initial CSF shunt infection was consistently associated with a higher hazard of reinfection in this study and suggests the feasibility of controlling and standardizing the surgical approach (shunt removal with EVD placement). Considerably more variation and equipoise exists in the duration and selection of intravenous antibiotic treatment. Further consideration should be given to the use of rifampin in the treatment of CSF shunt infection. High-quality studies of the optimal duration of antibiotic treatment are critical to the creation of evidence-based guidelines for CSF shunt infection treatment.