2. CSF shunt infections and their microbiological diagnosis Dr Roger Bayston MMedSci FRCPath University Hospital, Nottingham

3. Hydrocephalus Caused by obstruction of CSF pathways Can occur at any age Can follow meningitis (Incl TBM) haemorrhage ( SAH, PVH etc) trauma tumours congenital malformations intrauterine infections

4. Examples Congenital hydrocephalus Diagnosis: Hydrocephalus due to toxoplasmosis in utero

5. Hydrocephalus shunts Direction of flow

6. Routes of shunting VentriculoperitonealVentriculoatrial

7. Definition of shunt infection External: infection around the outside of the shunt. Failure to heal, or post-operative wound breakdown. Not a true shunt infection but a surgical wound infection. Internal: colonisation of the inner surfaces of the shunt tubing with or without involvement of the cerebral ventricles.

8. External “shunt infection” Internal (true) shunt infection Post -op erythema, swelling Bacteria growing on inside of shunt catheter About 5% of infections About 95% of infections

9. Incidence of shunt infection Cited as “10% of operations” But: children and adults: 3-6% Infants ≤ 6mo old, 10 - 25%

10. Medical consequences Ventriculitis Secondary infection from EVD Frequent relapse and need for re-operation Loculated ventricles Often presents as distal obstruction Peritonitis Peritoneal cysts, abscesses Loss of absorptive capacity

11. Causative organisms Staphylococcus epidermidis (and other CoNS) S aureus (some MRSA) Propionibacterium acnes Coryneforms Other gram positives Gram negatives Candida

12. Pathogenesis of shunt infections Adherence of bacteria to inner surface of shunt Bacterial proliferation (slow!) Biofilm development

13. Pathogenesis of shunt infection Time shunt surface Conditioning film Biofilm Exopolymer “slime” or PIA mic 1mg/L mic >500mg/L mic >50mg/L

14. Biofilm formation in shunts Staphylococci, SEM X 16300 Staphylococci, SEM X 5400

15. Why are biofilm phenotypes less susceptible to antibiotics? Nutrient depletion leads to problems with energy generation and transport This causes phenotype change to conserve energy All non - essential functions are down - regulated These include cell wall synthesis, protein synthesis and DNA replication This state is “dormant” or “SCV”

16. SCVs (Dormant biofilm phenotypes) SCVs usually revert to “textbook” appearance after a few subcultures They are identical on APIStaph and PFGE

17. SCVs from a recent VA case Blood culture Sub BA 48hr CSF broth subculture BA O/N

18. Gram film from fluid in removed shunt Longstanding shunt infections can give direct gram films showing pleomorphism and uneven staining

19. Diagnosis of VP shunt infection ≤ 6mo since operation Positive CRP Return of hydrocephalus (distal obstruction) Erythema over catheter track Positive shunt tap (Gram stain! and culture) Pyrexia

20. Laboratory diagnosis Blood culture - but rarely positive in VP In VA, usually positive in early stages but often negative in late - presenting infections. Problems with contaminants Serology: ASET for VA infections, not VP CRP for VP infections Shunt tap: can give normal CSF

21. CRP in VP shunt infection Operation5 days10 days15 days + 10mg/L

22. Examination of removed shunts Method A Shunt examined carefully Any pus or tissue on outside sampled Outside surface cleaned with a steret Fluid from inside of each component aspirated Gram film, aerobic + anaerobic culture, up to 7 days (more if bacteria seen) Method B Place removed shunt catheters into TSB, shake and incubate O/N then subculture onto BA

23. Examination of removed shunts: does the method make a difference? OrganismsMethod AMethod B CoNS422 S aureus13 Coryneform01 Mixed17 Gram film only +ve2 Negative251 Total3434 Clinically infected shunt88

24. Examination of removed shunts: does the method make a difference? OrganismsMethod AMethod B CoNS422 S aureus13 Coryneform01 Mixed17 Gram film only +ve2 Negative251 Total3434 Clinically infected shunt88

25. Prevention: Prophylactic antibiotics? Commonly used (85% of UK surgeons) Usually iv cephalosporin or gentamicin Neither reaches CSF ! Most staphylococci resistant ! No statistically valid trials! No evidence of efficacy (BSAC Working Party on Neurosurgical Infection)

26. Possible use of antimicrobial biomaterial

27. Antimicrobial shunts Bacteria adhere to the shunt, then die

28. Early clinical experience with antibacterial shunts Approx 30,000 used worldwide Expected infections: approx 3000 Reported so far (4.5yrs): 46 Three clinical trials reported so far: Govender et al 2003: J Neurosurg 99:831-839: Gram positive infection rate reduced from 16.7% to zero Aryan et al 2005: Child’s Nerv Syst 21: 56-61: Infection rate reduced from 15.2% to 3.1% (1 case) Scubbe et al 2005 (conference report): Infection rate reduced from 9% to 2% (291 cases, p=0.025)

29. The End