Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Acta Neurochirurgica
Published in: Acta Neurochirurgica 9/2017

01-09-2017 | Original Article - Brain Injury

A new model for biofilm formation and inflammatory tissue reaction: intraoperative infection of a cranial implant with Staphylococcus aureus in rats

Authors: Silke Glage, Silke Paret, Andreas Winkel, Meike Stiesch, André Bleich, Joachim K. Krauss, Kerstin Schwabe

Published in: Acta Neurochirurgica | Issue 9/2017

Login to get access

Abstract

Background

Implant failure is a severe and frequent adverse event in all areas of neurosurgery. It often involves infection with biofilm formation, accompanied by inflammation of surrounding tissue, including the brain, and bone loss. The most common bacteria involved are Staphylococcus aureus. We here test whether intraoperative infection of intracranial screws with Staphylococcus aureus would lead to biofilm formation and inflammatory tissue reaction in rats.

Methods

Two titanium screws were implanted in the cranium of Sprague-Dawley rats, anesthetized with xylazine (4 mg/kg) and ketamine (75 mg/kg). Prior to the implantation of the screws, Staphylococcus aureus was given in the drill holes; controls received phosphate-buffered saline (PBS). Rats were euthanized 2, 10 and 21 days after surgery to remove the screws for analysis of biofilm formation with a confocal laser scanning microscope. The surrounding tissue composed of soft tissue and bone, as well as the underlying brain tissue, was evaluated for inflammation, bone remodeling, foreign body reaction and fibrosis after H&E staining.

Results

Intraoperative application of Staphylococcus aureus leads to robust and stable biofilm formation on the titanium implants on days 10 and 21 after surgery, while no bacteria were found in controls. This was accompanied by a substantial inflammatory response of peri-implant tissue after infection, also affecting the underlying brain tissue.

Conclusions

Intraoperative infection of implants with Staphylococcus aureus in rats may be useful as a tool to model new implant materials and surfaces on biofilm formation and inflammatory tissue reaction in vivo.
Literature
1.
Alt V, Lips KS, Henkenbehrens C et al (2011) A new animal model for implant-related infected non-unions after intramedullary fixation of the tibia in rats with fluorescent in situ hybridization of bacteria in bone infection. Bone 48(5):1146–1153CrossRefPubMed
2.
Ammann TW, Bostanci N, Belibasakis GN, Thurnheer T (2013) Validation of a quantitative real-time PCR assay and comparison with fluorescence microscopy and selective agar plate counting for species-specific quantification of an in vitro subgingival biofilm model. J Periodontal Res 48(4):517–526CrossRefPubMed
3.
Amorena B, Gracia E (1999) Antibiotic susceptibility assay for Staphylococcus aureus in biofilms developed in vitro. J Antimicrob Chemother 44:43–55CrossRefPubMed
4.
Anderson JM, Rodriguez A, Chang DT (2008) Foreign body reaction to biomaterials. Semin Immunol 20(2):86–100CrossRefPubMed
5.
Arad E, Navon-Venezia S, Gur E, Kuzmenko B, Glick R, Frenkiel-Krispin D, Kramer E, Carmeli Y, Barnea Y (2013) Novel rat model of methicillin-resistant Staphylococcus aureus-infected silicone breast implants: a study of biofilm pathogenesis. Plast Reconstr Surg 131(2):205–214CrossRefPubMed
6.
Archer NK, Mazaitis MJ, Costerton JW, Leid JG, Powers ME, Shirtliff ME (2011) Staphylococcus aureus Biofilms. Properties, regulation and roles in human disease. Virulence 25:445–459CrossRef
7.
Astrup LB, Nielsen MV, Iburg TM, Leifsson PS, Jensen HE, Nielsen OL, Agerholm JS (2013) Brain microabscesses in a porcine model of Staphylococcus aureus sepsis. Acta Vet Scand 55(1):76CrossRefPubMedPubMedCentral
8.
Bakaletz LO (2004) Developing animal models for polymicrobial diseases. Nat Rev Microbiol 2(7):552–568CrossRefPubMed
9.
Berendt T, Byren I (2004) Bone and joint infection. Clin Med 4(6):510–518CrossRef
10.
Bjerknes S, Skogseid IM, Sæhle T, Dietrichs E, Toft M (2014) Surgical site infections after deep brain stimulation surgery: frequency, characteristics and management in a 10-year period. PLoS One 9(8):1–9CrossRef
11.
Braxton EE, Ehrlich GD, Hall-Stoodley L, Stoodley P, Veeh R, Fux C, Hu FZ, Quigley M, Post JC (2005) Role of biofilms in neurosurgical device-related infections. Neurosurg Rev 28(4):249–255CrossRefPubMed
12.
Campoccia D, Montanaro L, Arciola CR (2013) A review of the clinical implications of anti-infective biomaterials and infection-resistant surfaces. Biomaterials 34(33):8018–8029CrossRefPubMed
13.
Chen WH, Kang YJ, Dai LY, Wang B, Lu C, Li J, Lü GH (2014) Bacteria detected after instrumentation surgery for pyogenic vertebral osteomyelitis in a canine model. Eur Spine J 23(4):838–845CrossRefPubMed
14.
Costerton JW (1999) Bacterial bofilms: a common cause of persistent infections. Science 284(1999):1318–1322CrossRefPubMed
15.
Darouiche RO (2004) Treatment of infections associated with surgical implants. N Engl J Med 350(14):1422–1429CrossRefPubMed
16.
Doll K, Jongsthaphongpun KL, Stumpp NS, Winkel A, Stiesch M (2016) Quantifying implant-associated biofilms: comparison of microscopic, microbiologic and biochemical methods. J Microbiol Methods 130:61–68CrossRefPubMed
17.
Elter C, Heuer W, Demling A, Hannig M, Heidenblut T, Bach F-W, Stiesch-Scholz M (2008) Supra- and subgingival biofilm formation on implant abutments with different surface characteristics. Int J Oral Maxillofac Implants 23(2):327–334PubMed
18.
19.
Freire M (2011) Development of an animal model for Aggregatibacter actinomycetemcomitans biofilm-mediated oral osteolytic infection: a preliminary study. J Periodontol 82(5):778–789CrossRefPubMedPubMedCentral
20.
Garrido V, Collantes M, Barberan M, Penuelas I, Arbizu J, Amorena B, Grillo M-J (2014) In vivo monitoring of Staphylococcus aureus biofilm infections and antimicrobial therapy by [18F]fluoro-deoxyglucose-microPET in a mouse model. Antimicrob Agents Chemother 58(11):6660–6667CrossRefPubMedPubMedCentral
21.
22.
Giannakopoulou A, Grigoriadis N, Bekiari C, Lourbopoulos A, Dori I, Tsingotjidou AS, Michaloudi H, Papadopoulos GC (2013) Acute inflammation alters adult hippocampal neurogenesis in a multiple sclerosis mouse model. J Neurosci Res 91(7):890–900CrossRefPubMed
23.
Haenle M, Zietz C, Lindner T, Arndt K, Vetter A, Mittelmeier W, Podbielski A, Bader R (2013) A model of implant-associated infection in the tibial metaphysis of rats. Sci World J (481975):1–8
24.
Hamani C, Lozano AM (2006) Hardware-related complications of deep brain stimulation: a review of the published literature. Stereotact Funct Neurosurg 84(5–6):248–251CrossRefPubMed
25.
Handreck A, Mall EM, Elger DA, Gey L, Gernert M (2015) Different preparations, doses, and treatment regimens of cyclosporine a cause adverse effects but no robust changes in seizure thresholds in rats. Epilepsy Res 112:1–17CrossRefPubMed
26.
Hanke ML, Kielian T (2012) Deciphering mechanisms of staphylococcal biofilm evasion of host immunity. FrontCellInfectMicrobiol 2(2235–2988 (Electronic)):62
27.
Heuer W, Elter C, Demling A, Neumann A, Suerbaum S, Hannig M, Heidenblut T, Bach FW, Stiesch-Scholz M (2007) Analysis of early biofilm formation on oral implants in man. J Oral Rehabil 34(5):377–382CrossRefPubMed
28.
Hollstein E-P (2003) Knöcherne Integration und Biokompatibilität eines neuen resorbierbaren Polymers zur Schraubenaugmentation im osteoporotischen Knochen. München, Ludwig-Maximilian-Universität, Inst. für Tierzucht, Bereich Versuchstierkunde, Diss
29.
Inzana JA, Schwarz EM, Kates SL, Awad HA (2015) A novel murine model of established staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery. Bone 72:128–136CrossRefPubMed
30.
Jörns A, Günther A, Hedrich H-J, Wedekind D, Tiedge M, Lenzen S (2005) Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat. Diabetes 54(7):2041–2052CrossRefPubMed
31.
Kasliwal MK, Tan LA, Traynelis VC (2013) Infection with spinal instrumentation: review of pathogenesis, diagnosis, prevention, and management. Surg Neurol Int 4(Suppl 5):S392–S403PubMedPubMedCentral
32.
Kerstens M, Boulet G, Van Kerckhoven M, Clais S, Lanckacker E, Delputte P, Maes L, Cos P (2015) A flow cytometric approach to quantify biofilms. Folia Microbiol (Praha) 60(4):335–342CrossRef
33.
Kesavalu L, Sathishkumar S, Bakthavatchalu V, Matthews C, Dawson D, Steffen M, Ebersole JL (2007) Rat model of polymicrobial infection, immunity, and alveolar bone resorption in periodontal disease. Infect Immun 75(4):1704–1712CrossRefPubMedPubMedCentral
34.
Li D, Gromov K, Soballe K, Puzas JE, O’Keefe RJ, Awad H, Drissi H, Schwarz EM (2008) Quantitative mouse model of implant-associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity. J Orthop Res 26:96–105CrossRefPubMedPubMedCentral
35.
Lietard C, Thébaud V, Besson G, Lejeune B (2008) Risk factors for neurosurgical site infections: an 18-month prospective survey. J Neurosurg 109(4):729–734CrossRefPubMed
36.
Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Stemberger A, Haas NP, Raschke M (2003) A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater 67:593–602CrossRefPubMed
37.
Mah TF, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9(1):34–39CrossRefPubMed
38.
Norden CW (1988) Lessons learned from animal models of osteomyelitis. Rev Infect Dis 10(1):103–110CrossRefPubMed
39.
Nowak I (2010) Die knöcherne Einheilung von Zirkon- und Titanimplantaten—Eine histologische und ultrastrukturelle Untersuchung. Düsseldorf, Heinrich-Heine-Universität, Klin. für Kiefer- und Plast. Gesichtschirurgie, Diss
40.
Peralta FDS, Pallos D, Queiroz CS, Ricardo LH (2015) Previous exposure to cyclosporine a and periodontal breakdown in rats. Arch Oral Biol 60(4):566–573CrossRef
41.
Sakka S, Coulthard P (2011) Implant failure: etiology and complications. Med Oral Patol Oral y Cirugía Bucal 16(1):42–44CrossRef
42.
43.
Sillay KA, Larson PS, Starr PA (2008) Deep brain stimulator hardware-related infections: incidence and management in a large series. Neurosurgery 62(2):360–366CrossRefPubMed
44.
Silva MT (2011) Macrophage phagocytosis of neutrophils at inflammatory/infectious foci: a cooperative mechanism in the control of infection and infectious inflammation. J Leukoc Biol 89(5):675–683CrossRefPubMed
45.
Snowden JN, Beaver M, Smeltzer MS, Kielian T (2012) Biofilm-infected intracerebroventricular shunts elicit inflammation within the central nervous system. Infect Immun 80(9):3206–3214CrossRefPubMedPubMedCentral
46.
Stavrakis AI, Loftin AH, Lord EL, Hu Y, Manegold JE, Dworsky EM, Scaduto AA, Bernthal NM (2015) Current animal models of postoperative spine infection and potential future advances. Front Med 2:34CrossRef
47.
Stucker F, Ackermann D (2011) Immunsuppressiva—Wirkungen, nebenwirkungen und interaktionen. Ther Umschau 68(12):679–686CrossRef
48.
49.
Tonetti MS (2000) Schmid J (1994) pathogenesis of implant failures. Periodontol 4:127–138CrossRef
50.
Trindade R, Albrektsson T, Tengvall P (2014) Foreign body reaction to biomaterials: On mechanisms for buildup and breakdown of osseointegration. Clin Implant Dent Relat Res 1–12
51.
52.
Veerachamy S, Yarlagadda T, Manivasagam G, Yarlagadda PK (2014) Bacterial adherence and biofilm formation on medical implants: a review. Proc Inst Mech Eng H 228(10):1083–1099CrossRefPubMed
53.
Verma RK, Rajapakse S, Meka A, Hamrick C, Pola S, Bhattacharyya I, Nair M, Wallet SM, Aukhil I, Kesavalu L (2010) Porphyromonas gingivalis and treponema denticola mixed microbial infection in a rat model of periodontal disease. Interdiscip Perspect Infect Dis. doi:10.​1155/​2010/​605125
54.
Voges J, Hilker R, Bötzel K et al (2007) Thirty days complication rate following surgery performed for deep-brain-stimulation. Mov Disord 22(10):1486–1489CrossRefPubMed
55.
Xiong J, Burkovetskaya M, Karpuk N, Kielian T (2012) IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection. ASN Neuro 4(3):175–185CrossRef
56.
Metadata
Title
A new model for biofilm formation and inflammatory tissue reaction: intraoperative infection of a cranial implant with Staphylococcus aureus in rats
Authors
Silke Glage
Silke Paret
Andreas Winkel
Meike Stiesch
André Bleich
Joachim K. Krauss
Kerstin Schwabe
Publication date
01-09-2017
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 9/2017
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-017-3244-7

Other articles of this Issue 9/2017

Acta Neurochirurgica 9/2017 Go to the issue

Original Article - Vascular

Efficacy, safety, and clinical outcome of modern mechanical thrombectomy in elderly patients with acute ischemic stroke

Original Article - Vascular

CTA analysis and assessment of morphological factors related to rupture in 413 posterior communicating artery aneurysms

Case Report - Functional

Painful spasms in facial, masticatory, and motor ocular muscles reversed after microvascular decompression of a neurovascular conflict at brainstem

Case Report - Neurosurgical Techniques

Transtubular excisional biopsy as a rescue for a non-diagnostic stereotactic needle biopsy—case report and literature review

Erratum

Erratum to: an update on addressing important peripheral nerve problems: challenges and potential solutions

Original Article - Spine

Treatment of atlanto-axial subluxation secondary to rheumatoid arthritis by short segment stabilization with polyaxial screws