Antibiotic-impregnated shunt catheters decrease the incidence of shunt infection in the treatment of hydrocephalus Daniel M. Sciubba, MD George I. Jallo, M.D. Johns Hopkins University Department of Neurological Surgery

Shunt Infection North American infection rate averages 5-15% Majority occur less than 4 months postoperatively Associated with reduced IQ and school performance, increased risk of seizures, and psychomotor retardation Common cause of shunt failure with its associated increased risk of morbidity and mortality

Etiology of Infection Colonization by skin flora at the time of implantation Majority caused by gram positive cocci, with coagulase-negative staphylococci species predominating Antibiotic-impregnated shunt (AIS) systems have been shown to decrease colonization of shunt components by staphylococcal species* Our study: evaluate incidence of shunt infection after introduction of an AIS system into a pediatric hydrocephalus population *Bayston R, et al. J Neurosurg 1997 *Kockro R, et al. J Med Microbiol 2000 *Hampl J, et al. Infection 2003 *Govender S, et al. J Neurosurg 2003

Methods Retrospective chart review of all pediatric patients undergoing CSF shunt insertion over a 3-year period between 11/01 and 3/04 18 months prior to October 2002, all CSF shunts included standard, non-impregnated shunt catheters 18 months following October 2002, all CSF shunts included antibiotic-impregnated shunt catheters 1 Patients were followed for 6 months, and all shunt-related complications, including shunt infection, were evaluated Independent association of AIS use with subsequent shunt infection was assessed via multivariate proportional hazards regression analysis 1Bactiseal; Codman, Johnson & Johnson, Boston, MA

Patient Population Total: 353 shunting procedures 55% male, 45% female Age: 1-16 years Etiology of hydrocephalus: congenital abnormality(27%) intracranial hemorrhage (25 %) myelodysplasia (15%) Dandy-Walker malformation (8%) tumor (7%) posterior fossa cyst(6%) meningitis(3%) aqueductal stenosis(1%) other etiology(9%) Communicating (52%), non-communicating (44%) VP (92%), VPl (5%), VA (3%)

Variable Non-ABx (n=208) ABx (n=145) p-value Age (yrs) 10.0 [ ]3.0 [ ]<0.01 Sex (% female)90 (43%)68 (47%) 0.50 Premature* 44 (21%) 53 (37%)<0.01 Etiology of Hydrocephalus Congenital58 (28%)39 (27%)0.98 Post-hemorrhagic41 (20%)47 (32%)<0.01 Myelodysplasia32 (15%)20 (14%)0.68 Dandy-Walker19 (9%)9 (6%)0.32 Tumor18 (10%)5 (3%)0.05 Post. Fossa Cyst12 (6%)8 (6%)0.99 Meningitis8 (4%)4 (3%)0.58 Aqueductal Stenosis2 (1%)2 (1%)0.99 Other17 (8%)14 (10%)0.99 Type of Hydrocephalus Non-communicating95 (46%)61 (42%)0.50 Communicating104 (50%)78 (54%)0.48 Unclear9 (4%)6 (4%)0.99 Initial shunt57 (27%)49 (34%)0.20 Shunt Revision151 (73%)96 (66%)0.20 Shunt type VP190 (91%)136 (94%)0.91 VPl10 (5%)7 (5%)0.99 VA8 (4%)2 (1%)0.17 Valve Type Programmable28 (14%)48 (33%)<0.01 Set Pressure130 (63%)74 (51%) 0.03 Unspecified50 (24%)23 (16%)0.06

Variable Non-ABx (n=208) ABx (n=145) p-value Age (yrs) 10.0 [ ]3.0 [ ]<0.01 Sex (% female)90 (43%)68 (47%) 0.50 Premature* 44 (21%) 53 (37%)<0.01 Etiology of Hydrocephalus Congenital58 (28%)39 (27%)0.98 Post-hemorrhagic41 (20%)47 (32%)<0.01 Myelodysplasia32 (15%)20 (14%)0.68 Dandy-Walker19 (9%)9 (6%)0.32 Tumor18 (10%)5 (3%)0.05 Post. Fossa Cyst12 (6%)8 (6%)0.99 Meningitis8 (4%)4 (3%)0.58 Aqueductal Stenosis2 (1%)2 (1%)0.99 Other17 (8%)14 (10%)0.99 Type of Hydrocephalus Non-communicating95 (46%)61 (42%)0.50 Communicating104 (50%)78 (54%)0.48 Unclear9 (4%)6 (4%)0.99 Initial shunt57 (27%)49 (34%)0.20 Shunt Revision151 (73%)96 (66%)0.20 Shunt type VP190 (91%)136 (94%)0.91 VPl10 (5%)7 (5%)0.99 VA8 (4%)2 (1%)0.17 Valve Type Programmable28 (14%)48 (33%)<0.01 Set Pressure130 (63%)74 (51%) 0.03 Unspecified50 (24%)23 (16%)0.06

Results 25 (12%) patients with non-impregnated catheters experienced shunt infection within 6-month follow up period Two (1.4%) patients with antibiotic-impregnated catheters experienced shunt infection within the 6- month follow-up period (p<0.01) Adjusting for inter-cohort differences in age, prematurity and post-hemorrhagic HCP via multivariate analysis, AIS catheters were independently associated with a: 2.4-fold decreased likelihood of shunt infection (RR, 0.41; 95%CI, , p<0.01)

Organism Non-ABx (n=25) ABx (n=2) Staphylococcus, coagulase negative131 Staphylococcus aureus31 Streptococcus, group B1 Enterococcus faecium1 Corynebacteria spp.2 Gram negative rod4 Candida spp.1 Infectious Agent

Incidence of shunt infection as a function of time after insertion

Conclusions Significant reduction in CSF shunt infection was noted after introduction of an AIS system into a pediatric hydrocephalus population This reduction occurred over a six month postoperative follow up, encompassing the period of early infections which make up the majority of all shunt infections Future double-blinded randomized controlled trials must be conducted to further corroborate the results obtained from this retrospective study