Health Care associated infection/pathology of the Central Nervous System

1. Health Care associated infection/pathology of the Central Nervous System Professor Mary Cafferkey Associate Professor of Clinical Microbiology, RCSI

2. Which infections? Acute infection • Encephalitis • Meningitis • Meningoencephalitis • Abscess Chronic infection Post-infectious and post-immunisation complications Transmissable spongioform encephalopathies

3. Scope • Procedure-Related • Other Intervention related • Medicinal substance • Transfusion of Blood or Blood products • Transplantation • Immunisation • Exposure to infection in a Health Care setting

4. Procedure-related • Lumbar puncture/Epidural anaesthesia • CNS electrodes • Procedures involving the Central Nervous System • Craniotomy • CSF Shunt placement/removal/revision • Operative procedures • Exploration/lobectomy/abscess drainage/excision of tumour etc

5. Lumbar puncture/epidural anaesthesia etc. • Risk • Organism • Prevention • Diagnosis and management

6. Lumbar Puncture With aseptic technique, negligible risk of meningitis following lumbar puncture Theoretical risk in patient with bacteraemia at the time of the procedure Image: Anaesthesiauk

7. Epidural Anaesthesia Short-term – for several days Subcutaneously tunnelled may be left in place for longer (months) Very low risk of infection with careful aseptic technique; ? Risk with Bacteraemia Case reports and small series in the literature Images: Wikipedia.org

8. Spinal anaesthesia Very low risk of infection with careful aseptic technique ? Risk with bacteremia Case reports & small series in the literature

9. CNS electrodes • Spinal cord, brain • Very low risk with careful aseptic technique • The literature in the last 10+ years has concentrated on the risk of transmissable spongioform encephalopathies (TSEs)

10. Surgical Procedures involving the CNS • Craniotomy • CSF Shunt placement/removal/revision • Operative procedures • Exploration/lobectomy/abscess drainage/excision of tumour etc

11. CSF Shunt placed: • Treatment of hydrocephalus • To relieve pressure in PTC/IIH Shunt or access device: • To administer cytotoxic agents or, rarely, painkillers (morphine)

14. Ventriculoperitoneal (VP) and ventroculoatrial (VA) shunts

17. Ommaya Reservoir

18. Instillation of agent into Ommaya Reservoir

19. Indications for shunt placement:Paediatrics • Hydrocephalus • Congenital • Aqueductal stenosis, Chiari malformations, Cysts, vascular malformations • Acquired • Postmeningitic or post-inflammatory, IVH, Tumour • Hydraencephaly

20. Indications for shunt placement:Adults Conen et al., Clin Infect Dis 2008:47:73-82

21. Pople I. J Neurol Neurosurg Psychiatry 2002;73:i17-22

22. CNS Shunt complications • Infection • Obstruction • Proximal end, protein accumulation • [Distal end, protein accumulation] • Valve obstruction or malfunction • Catheter disconnection, kinking or migration • Overdrainage • Extra-axial fluid collection and brain compression • Subdural haematoma • Chiara 1 malformation • Slit Ventricle • Intraventricual haemorrhage

23. CNS Shunt Complications Substantial morbidity and risk of mortality Long term complications • Cognitive defects • Neurological problems • Death

24. Criteria for nosocomial Shunt Infection (modified CDC) • Growth of a pathogen in the CSF, from the shunt tip, or in wounds overlying the implanted material OR • Fever (>38oC), headache, neck stiffness, cranial nerve signs or irritability without another recognised cause, physician initiation of antimicrobial therapy, and CSF leukocyte count >5 x106/L, CSF protein >0.45g/L, CSF:Blood glucose ratio <0.5, organisms seen on CSF Gram stain, or organisms isolated from blood culture

26. CNS Shunt Infection Occurs in up to c.20% • Most common in the first 6 months after surgery • Most common in those shunted at <6 months • Risk may vary with cause of hydrocephalus • Incidence decreases with increasing age • The risk of infection is greater with a VA than with a VP shunt Independent risk factors • Previous shunt infection • Shunt dysfunction • Post-operative leakage of CSF • Experience of the neurosurgeon • Duration of the operative procedure

27. Ferguson SD et al, Observations Regarding Failure of Cerebrospinal Fluid Shunts Early After Implantation NeurosurgFocus 2007;22:E7University of Chicago Children’s Hospital • Retrospective review of 396 shunt placement procedures during an 8-year period • Data collected on patient age, race, indication for shunting, origin of hydrocephalus, shunt type, date of shunt revision or removal, and number of subsequent revisions • For failure due to shunt malfunction – data was obtained on the cause of failure (obstruction of valve, proximal catheter or distal catheter) • For cases of infection, the identity of the causative organism was recorded

28. Ferguson SD et al, Observations Regarding Failure of Cerebrospinal Fluid Shunts Early After Implantation NeurosurgFocus 2007;22:E7University of Chicago Children’s Hospital • 396 shunt procedures • 116 shunts failed (90 patients) • M:59%, non-white 54.3% • Shunts were placed for hydrocephalus 87.9%, PTC 12.1% • Mean survival time of newly placed shunts - 6.3 +/- 11.8 months • Shunt failures • Malfunction 83 (71.5%) • Infection 33 (28.5%) • Pathogens • Staph epi 54% • MSSA 25% • MRSA 12% • Ps aeruginosa 3% • Others inc Serratia & Corynebacterium 6%

29. Ferguson SD et al, Observations Regarding Failure of Cerebrospinal Fluid Shunts Early After Implantation NeurosurgFocus 2007;22:E7University of Chicago Children’s Hospital • 116 shunts failed • Mean survival time of newly placed shunts - 6.3 +/- 11.8 months • Malfunction 7.1+/- 12.2 • Infection 4.3 +/- 10.7 • Shunt failures • Malfunction 83 (71.5%) • Infection 33 (28.5%) • The origins of hydrocephalus were similar in the 2 groups • Shunts for Hydrocephalus longer survival than for PTC (p = 0.051) • Shunts placed age 0-6 mo shorter survival than those after age 6 mo (p = 0.067) • Shunts with malfunction almost x2 as likely to last longer than 6 months than with infection (p<0.05) • Mean shunt survival period almost 7 times greater in white than non-white, 20.4 vs 3.1 mo, ANOVA p <0.05

30. Clin Infect Dis 2008:47:73-82

32. Findings • 48 (62%) of infections within 1 month of surgery • 61 (78%) had fever • 35 (45%) had neck stiffness • 38 (49%) had local signs of inflammation • 80% had CSF leukocyte count >5 x106/L • 81% had elevated CSF lactate • 52% had CSF:blood glucose ratio <0.5 • 58% had CSF protein >0.45g/L Conen et al., Clin Infect Dis 2008:47:73-82

33. Conen et al., Clin Infect Dis 2008:47:73-82

34. Conen et al., Clin Infect Dis 2008:47:73-82

35. Sciubba DM et al, Factors contributing to the Medical Costs of Cerebrospinal Fluid Shunt Infection Treatment in Pediatric Patients with Standard Shunt Components Compared with Antibiotic-impregnated Components NeurosurgFocus 2007;22:E9 Johns Hopkins • Retrospective review • Pediatric patients age range 1-16 years who underwent shunt insertion for hydrocephalus over a 3 year period • Patient FU 12 mo after surgery. • N = 211 patients had 353 shunting procedures; • M:F 195:158, 55%:45% • Shunt type • VP 326 (92%), VPL 17 (5%), VA 10 (3%) • The AIS cohort were younger, more frequently premature, had a greater incidence of ICH and more frequently had programmable valves

36. 211 patients had 353 shunting procedures; 208 standard shunts, 145 AISs (if full system, clindamycin and rifampicin) After adjusting for intercohort differences, on multivariate analysis, AIS catheters were independently associated with a 2.4-fold decreased likelihoood of shunt infection (relative risk = 0,041, 95% CI 0.32-0.52, p<0.01 Sciubba DM et al, Factors contributing to the Medical Costs of Cerebrospinal Fluid Shunt Infection Treatment in Pediatric Patients with Standard Shunt Components Compared with Antibioticimpregnated Components NeurosurgFocus 2007;22:E9

37. Tuan TJ et al. Treatment and Microbiology of Repeated Cerebrospinal Fluid Shunt Infections in Children Ped Inf Dis J 2011;30 731-735University of California at San Francisco • n = 31 with second shunt infections (SI-2) • Age <6 mo at initial shunt placement 81% • Male 77% • VP shunt 71% • 18 developed SI-3 (60%) and 8, SI-4 (47%) • The median time to SI-3 was 477 days (range 2-828 days) and SI-4 was 2137 days (range 9-2137 days) • Gram positive organisms predominated (SI-2 93%, SI-3 94%) “Children with SI-2 experience high subsequent reinfection rates with a long time to reinfection”

38. Prevention of CNS shunt infections • Surgical site preparation • Prophylactic antibiotics • “Care bundle” • Antimicrobial impregnanted catheters • Antimicrobial impregnanted sutures

39. Surgical prophylaxis Neurosurgery • Prophylaxis is not effective in reducing infection rates with intracranial pressure monitors – retrospective analysis n = 215, J Neurol Neurosurg Psych 2000;69:381 Recommended for • Clean non-implant surgery (e.g., craniotomy) • Clean, contaminated surgery (through sinuses or oro/nasopharynx) • Insertion of CSF shunt

40. Clean, non-implant Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy, Antimicrobial prophylaxis in neurosurgery and after head injury Lancet 1994;344:1547-51 cefazolin 1-2G iv single dose alternative vancomycin 1 g iv single dose

41. Clean, contaminated • Clean, contaminated (through sinuses or oro/nasopharynx) • clindamycin 900mg iv single dose, or amoxicillin-clavulinic acid 1.2g single dose or cefuroxime 1.5g iv single dose plus metrondidazole 500mg iv single dose

42. CSF Shunt Insertion • Meta-analysis suggests benefit of prophylaxis (Cochrane Database 3:CD005365, 2006) • Cefazolin 1-2g iv single dose, alternative vancomycin 1g iv single dose • In a hospital with a high prevalence of MRSA infection, vancomycin was more effective (J Hosp Infect 2008;69:337

43. Quality Improvement/”Care Bundle”

45. Management of Infection

47. Causes of HCA meningitis/encephalitis/ encephalopathy

48. The Patient • Exposure/Cross-infection • Varicella-zoster, influenza virus, measles virus, Mycobacterium tuberculosis, (N. meningitidis) • Transfusion/Transplantation • Cytomegalovirus, Epstein-Barr Virus, West Nile Virus, Tick-borne encephalitis, rabies, T. pallidum,R. rickettsiae, C. neoformans, Coccidioidesspp, H. capsulatum,Toxoplasmagondii, human parvovirus (parvovirus B19), CJD, vCJD Black : N. Europe

49. Transplant Recipients HCAInfections that may involve the CNS Recipients of: Haemopoietic cell transplantation – HCT Solid Organ transplant – SOT • Cytomegalovirus – SOT and HCT • Toxoplasma gondii - HCT Well established and evidence based prophylaxis regimens

50. West Nile Virus • A flavivirus transmitted by mosquitos, blood transfusions, transplanted organs and breast feeding” (Sanford Guide Antimicrobial Therapy 2011) • recipients of kidney or pancreas transplants, and hematopoietic stem cell transplants • In one cluster (4 organ recipients), blood transfusion was the probable source of WNV viremia in the donor • Blood is now tested in the USA due to increased serum lipase in 11/17 cases