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.

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.

Maternal and neonatal IgG against Klebsiella pneumoniae are associated with broad protection from neonatal sepsis: a case-control study of hospitalized neonates in Botswana.

Sepsis is the leading postnatal cause of neonatal mortality worldwide. Globally Klebsiella pneumoniae is the leading cause of sepsis in hospitalized neonates. This study reports development and evaluation of ELISA for anti-Klebsiella IgG using dried blood spot samples and evaluates the association of anti-Klebsiella IgG (anti-Kleb IgG) antibodies in maternal and neonatal samples and the risk of neonatal sepsis. Neonates and their mothers were enrolled at 0-96 hours of life in the neonatal unit of a tertiary referral hospital in Gaborone, Botswana and followed until death or discharge to assess for episodes of blood culture-confirmed neonatal sepsis. Neonates with sepsis had significantly lower levels of Kleb-IgG compared to neonates who did not develop sepsis (Mann-Whitney U, p=0.012). Similarly, samples from mothers of neonates who developed sepsis tended to have less Kleb-IgG compared to mothers of controls (p=0.06). The inverse correlation between Kleb-IgG levels and all-cause bacteremia suggests that maternal Kleb-IgG is broadly protective through cross-reactivity with common bacterial epitopes. These data support the continued use of immunoglobulin assays using DBS samples to explore the role of passive immunity on neonatal sepsis risk and reaffirm the critical need for research supporting the development of maternal vaccines for neonatal sepsis.

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.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.