The infection of cerebrospinal fluid draining devices (CDD), development of shunt infection prevention model and protocol

• Thesis title in Czech: Experimentální model a protokol předcházení infekčním komplikacím drenážních systémů mozkomíšního moku
• Thesis title in English: The infection of cerebrospinal fluid draining devices (CDD), development of shunt infection prevention model and protocol
• Key words: hydrocefalus, infekce, zkrat, mozkomíšní mok
• English key words: hydrocephalus, infection, shunt, cerebrospinal fluid
• Academic year of topic announcement: 2019/2020
• Thesis type: dissertation
• Thesis language: angličtina
• Department: Department of Neurosurgery (13-380)
• Supervisor: doc. MUDr. Petr Libý, Ph.D.
• Author: hidden - assigned by the advisor
• Date of registration: 29.10.2019
• Date of assignment: 29.10.2019
• Advisors: doc. MUDr. Michal Tichý, CSc.

Guidelines

retrospektivní studie, identifikátory, experimentální model prevence infekce zkratů, prospektivni studie, vytvoření protokolu, klinická aplikace

References

1. Borgbjerg BM, Gjerris F, Albeck MJ, Borgesen SE. Risk of infection after cerebrospinal fluid shunt: an analysis of 884 first-time shunts. Acta Neurochir (Wien). 1995; 136(1±2):1±7. PMID: 8748819.
2. Cochrane DD, Kestle JR. The influence of surgical operative experience on the duration of first ventriculoperitoneal shunt function and infection. Pediatr Neurosurg. 2003; 38(6):295±301. doi: 70413. https://doi.org/10.1159/000070413 PMID: 12759508.
3. James G, Hartley JC, Morgan RD, Ternier J. Effect of introduction of antibiotic-impregnated shunt catheters on cerebrospinal fluid shunt infection in children: a large single-center retrospective study. J Neurosurg Pediatr. 2014; 13(1):101±6. https://doi.org/10.3171/2013.10.PEDS13189 PMID: 24206346.
4. Kestle JR, Holubkov R, Douglas Cochrane D, Kulkarni AV, Limbrick DD Jr., Luerssen TG, et al. A new Hydrocephalus Clinical Research Network protocol to reduce cerebrospinal fluid shunt infection. J Neurosurg Pediatr. 2016; 17(4):391±6. https://doi.org/10.3171/2015.8.PEDS15253 PMID: 26684763.
5. Kestle JR, Riva-Cambrin J, Wellons JC 3rd, Kulkarni AV, Whitehead WE, Walker ML, et al. A standardized protocol to reduce cerebrospinal fluid shunt infection: the Hydrocephalus Clinical Research Network Quality Improvement Initiative. J Neurosurg Pediatr. 2011; 8(1):22±9. https://doi.org/10.3171/2011.4.PEDS10551 PMID: 21721884; PubMed Central PMCID: PMCPMC3153415.
6. Konstantelias AA, Vardakas KZ, Polyzos KA, Tansarli GS, Falagas ME. Antimicrobial-impregnated and-coated shunt catheters for prevention of infections in patients with hydrocephalus: a systematic review and meta-analysis. J Neurosurg. 2015; 122(5):1096±112. https://doi.org/10.3171/2014.12.JNS14908 PMID: 25768831.
7. Prusseit J, Simon M, von der Brelie C, Heep A, Molitor E, Volz S, et al. Epidemiology, prevention and management of ventriculoperitoneal shunt infections in children. Pediatr Neurosurg. 2009; 45(5):325±36. https://doi.org/10.1159/000257520 PMID: 19907195.
8. Simon TD, Hall M, Riva-Cambrin J, Albert JE, Jeffries HE, Lafleur B, et al. Infection rates following initial cerebrospinal fluid shunt placement across pediatric hospitals in the United States. Clinical article. J Neurosurg Pediatr. 2009; 4(2):156±65. https://doi.org/10.3171/2009.3.PEDS08215 PMID: 19645551;PubMed Central PMCID: PMCPMC2896258.
9. Parker SL, McGirt MJ, Murphy JA, Megerian JT, Stout M, Engelhart L. Comparative effectiveness of antibiotic-impregnated shunt catheters in the treatment of adult and pediatric hydrocephalus: analysis of 12,589 consecutive cases from 287 US hospital systems. J Neurosurg. 2015; 122(2):443±8. https://doi.org/10.3171/2014.10.JNS13395 PMID: 25415066.
10. Klimo P Jr., Van Poppel M, Thompson CJ, Baird LC, Duhaime AC, Flannery AM, et al. Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with hydrocephalus: a systematic review and meta-analysis. J Neurosurg Pediatr. 2014; 14 Suppl 1:44±52. https://doi.org/10.3171/2014.7.PEDS14326 PMID: 25988782.
11. Sarmey N, Kshettry VR, Shriver MF, Habboub G, Machado AG, Weil RJ. Evidence-based interventions to reduce shunt infections: a systematic review. Childs Nerv Syst. 2015; 31(4):541±9. https://doi.org/10.1007/s00381-015-2637-2 PMID: 25686893.
12. Klimo P Jr., Thompson CJ, Baird LC, Flannery AM, Pediatric Hydrocephalus Systematic R, Evidence-Based Guidelines Task F. Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 7: Antibiotic-impregnated shunt systems versus conventional shunts in children: a systematic review and meta-analysis. J Neurosurg Pediatr. 2014; 14 Suppl 1:53±9. https://doi.org/10.3171/ 2014.7.PEDS14327 PMID: 25988783.
13. Klimo P Jr., Thompson CJ, Ragel BT, Boop FA. Antibiotic-impregnated shunt systems versus standard shunt systems: a meta- and cost-savings analysis. J Neurosurg Pediatr. 2011; 8(6):600±12. https://doi.org/10.3171/2011.8.PEDS11346 PMID: 22132919.
14. Parker SL, Anderson WN, Lilienfeld S, Megerian JT, McGirt MJ. Cerebrospinal shunt infection in patients receiving antibiotic-impregnated versus standard shunts. J Neurosurg
15. van Lindert, Bilsen, Flier, Kolwijck, Delye, Oever. Topical vancomycin reduces the cerebrospinal fluid shunt infection rate: A retrospective cohort study. PLoS One. 2018 Jan 9;13(1):e0190249. doi: 10.1371/journal.pone.0190249. eCollection 2018.
16. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017.
17. Infections of cerebrospinal fluid shunts and other devices, Larry M Baddour, MD, FIDSA, FAHAPatricia M Flynn, MDThomas Fekete, MD; uptodate.com
18. Ragel BT, Browd SR, Schmidt RH. Surgical shunt infection: significant reduction when using intraventricular and systemic antibiotic agents. J Neurosurg. 2006; 105(2):242±7. https://doi.org/10.3171/jns.2006.105.2.242 PMID: 17219829.
19. E. Gathura, M.B.B.s., Dan Poenaru, M.D., Richard Bransford, M.D., anD a. LEland Albright, M.D. Outcomes of ventriculoperitoneal shunt insertion in Sub-Saharan Africa. J Neurosurg Pediatrics 6:000–000, 2010
20. Adeloye A: Management of infantile hydrocephalus in Central Africa. Trop Doct 31:67–70, 200
21. Mwang’ombe NJM, Omulo T: Ventriculoperitoneal shunt surgery and shunt infections in children with non-tumour hydrocephalus at the Kenyatta National Hospital, Nairobi. East Afr Med J 77:386–390, 2000
22. Leidinger A, Piquer J, Kim EE, Nahonda H, Qureshi MM, Young PH. Treating Pediatric Hydrocephalus at the Neurosurgery Education and Development Institute: The Reality in the Zanzibar Archipelago, Tanzania. World Neurosurg. 2018 Jun 18. pii: S1878-8750(18)31265-8. doi: 10.1016/j.wneu.2018.06.050.
23. Enger PO, Svendsen F, Wester K: CSF shunt infections in children: experiences from a population-based study. Acta Neurochir (Wien) 145:243–248, 2003
24. Wells EM, Packer RJ. Pediatric brain tumors. Continuum (Minneap Minn). 2015 Apr;21(2 Neuro-oncology):373-96. doi: 10.1212/01.CON.0000464176.96311.d1.
25. Faraci M et al. Intensive care unit admission in children with malignant or nonmalignant disease: incidence, outcome, and prognostic factors: a single-center experience. J Pediatr Hematol Oncol. 2014 Oct;36(7):e403-9. doi: 10.1097/MPH.0000000000000048.
26. Tully HM, Dobyns WB. Infantile hydrocephalus: a review of epidemiology, classification and causes. Eur J Med Genet. 2014 Aug;57(8):359-68. doi: 10.1016/j.ejmg.2014.06.002. Epub 2014 Jun 13.
27. Lin CT1,2, Riva-Cambrin JK. Management of posterior fossa tumors and hydrocephalus in children: a review. Childs Nerv Syst. 2015 Oct;31(10):1781-9. doi: 10.1007/s00381-015-2781-8. Epub 2015 Sep 9.
28. George R, Leibrock L, Epstein M: Long-term analysis of cerebrospinal fluid shunt infections: A 25-year experience. J Neurosurg 1979;51: 804–811.
29. Lund-Johansen M, Svendsen F, Wester K: Shunt failures and complications in adults as related to shunt type, diagnosis, and the experience of the surgeon. Neurosurgery 1994;35: 839–844.
30. Kritsotakis EI et al. Case-mix adjustment approach to benchmarking prevalence rates of nosocomial infection in hospitals in Cyprus and Greece. Infect Control Hosp Epidemiol. 2008 Aug;29(8):685-92. doi: 10.1086/588704.
31. Ramanan M, Lipman J, Shorr A, Shankar A. A meta-analysis of ventriculostomy-associated cerebrospinal fluid infections. BMC Infect Dis 2015; 15:3.
32. Simon TD, Butler J, Whitlock KB, et al. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study. J Pediatr 2014; 164:1462.
33. van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial meningitis. N Engl J Med 2010; 362:146.
34. M. Gmeiner et al. Long-term mortality rates in pediatric hydrocephalus—a retrospective single-center study. Childs Nerv Syst. 2017 Jan;33(1):101-109. doi: 10.1007/s00381-016-3268-y. Epub 2016 Oct 20.
35. Tuli S1, Tuli J, Drake J, Spears J. Predictors of death in pediatric patients requiring cerebrospinal fluid shunts. J Neurosurg. 2004 May;100(5 Suppl Pediatrics):442-6.
36. Kestle JR. Management of shunt infections: a multicenter pilot study. J Neurosurg. 2006 Sep;105(3 Suppl):177-81.
37. Kulkarni AV, Rabin D, Lamberti-Pasculli M, Drake JM: Repeat cerebrospinal fluid shunt infection in children. Pediatr Neurosurg 35:66–71, 2001
38. Li Z et al. Empirical Combination Antibiotic Therapy Improves the Outcome of Nosocomial Meningitis or Ventriculitis in Neuro-Critical Care Unit Patients. Surg Infect (Larchmt). 2016 Aug;17(4):465-72. doi: 10.1089/sur.2015.060. Epub 2016 Apr 22.
39. Reichert MC, Medeiros EA, Ferraz FA. Hospital-acquired meningitis in patients undergoing craniotomy: Incidence, evolution, and risk factors. Am J Infect Control 2002;30: 158–164.
40. Klastersky J, Mombelli G, Coppens L, et al. Post neurosurgery gram-negative bacillary meningitis. J Infect 1981; 3:45–51.
41. Bayston R, Bannister C, Boston V (1990) A prospective randomized controlled trial of antimicrobial prophylaxis in hydrocephalus shunt surgery. Z Kinderchir [Suppl 1] 45:5–7
42. Leroux P, Howard MA, Winn HR (1990) Vancomycin pharmacokinetics in hydrocephalic shunt prophylaxis and relationship to ventricular volume. Surg Neurol 34:366–372

Preliminary scope of work

viz. anglicky

Preliminary scope of work in English

Introduction: Infections of shunts in pediatric neurosurgery are relatively frequent and possess significant burden for the patient and caregivers. The average shunt infection rate is about 5-15%, although lower and higher rates are reported. Analysis of CDD infection rate along with meticulous CDD infection prevention protocol are missing in our institution.

Hypothesis: Shunt infection rate can be lowered by application of a new institutional shunt infection protocol (ISIP) based on retrospective analysis of risk factors related to our institution.
Experimental surgical part: The work can be done only in a clinical and surgical settings, however we might foresee to expand it into laboratory experimental work focusing on the CSF parameters and formation of biofilm on catheters during infection (e.g. Interleukin-10, Interleukin-17, activated macrophages, serum lipoproteins). The experimental surgical part will be based on applied surgical technique and elimination of retrospectively analysed risk factors. We will then compare the retrospective cohort of patients with the prospective to confirm our hypothesis. The work has a great potential to obtain important epidemiological and clinical data, to develop scientific skills, to improve surgical technique, confirm position of minimally invasive techniques, e.g. neuroendoscopy. None such a project focused on large case-load pediatric neurosurgical center exists in the Czech Republic. Very importantly, we expect the work to expand experimental boundaries to the bed of hundreds of our pediatric patients. We believe it is extremely important topic and wish to get support from the academics. We don’t expect to have any issues to publish the retrospective and prospective comparative parts in a peer-reviewed neurosurgically oriented journal. Moreover this project is based on international cooperation that should be valued by authorities of Charles University.

Material and Methods: In retrospective part of the study we would analyse our own institutional data considering CDD infection rate and factors leading to CDD infections during last five years. We would gather epidemiological and microbiological data and negative prognostic factors relevant to our institution and compared them to published pertinent literature. We would focus on a surgical technique and used materials (e.g. antibiotic impregnation of catheter) of CDD implantation. The obtained data should be applied in prospective study and in comparison to cohort of patients that were treated with endoscopy, thus without need of a CDD. We expect to use the data for meticulous selection of cases and procedures and improving the surgical technique. The foremost, the result should be used to develop new institutional CDD infection prevention protocol and improvement of minimal invasive surgical techniques with reduction of CDD infections. The results of both, retrospective and prospective studies should be published in peer-review journal.

Conflict of Interests & Ethical issues: We don’t expect any ethical issues by applying the ISIP.

Cooperations: In microbiological part we would cooperate with the Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital. And with Professor Alessandro Grimaldi, M.D., Ph.D., Chief of Dept. of Infectious diseases, University of L’Aquila and Professor Stefano Necozione, M.D., Ph.D., Chief of Dept. of Life, Health & Environmental Sciences University of L’Aquila.

Financial support:
The budget of the Department of Neurosurgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic