Preventing Deep Implant Related Infections

Orthopedic implant-related infections are a devastating complication for the patient, doctor, and healthcare system. Primary total joint arthroplasties have reported implant infection rates of 0.5-3% and revisions at 3-45%. Spinal fusion implant cases report rates of 3-15%. Other medical specialties and devices report even higher rates. 

The number of infections rises significantly with increased surgical volume. Additionally, infection rates continue to increase precipitously, despite advances in surgical technique, due to improved diagnoses and an increasing number of surgeries being performed on higher risk patient populations. 

In an environment of soaring health care costs, the adverse medical economics of implant-related infections cannot be overlooked. Especially when hospitals will no longer be reimbursed for the treatment of early acute implant related infections, a singular focus must be made to minimize these events. The healthcare system will look to device manufacturers to provide such solutions. 

Bacteria are ubiquitous in the operating room despite an illusion of a sterile environment. Bacteria exist in normal operating room air currents as well as on the patient. Most airborne bacteria are of human origin with an estimate of about 500,000-1,000,000 bacteria shed per individual per day [1]. 

The first step to microbial colonization of any implant is bacterial adhesion. This occurs early in the process after implantation if not already colonized. It is only after initial bacterial adhesion that the process of proliferation and biofilm production occur [2,3]. In addition to bacterial adhesion, proteins from the extracellular fluid also absorb on to the implant surfaces. Albumin absorbed onto material surfaces has demonstrated inhibitory effects on bacterial adhesion [3]. Gristina, in his description of “race to the surface”, notes that host cells can occupy space on the implant surface providing a defensive barrier against microbe attachment [2]. 

Once attached and adhered to the implant surface, the bacteria are no longer subject to attack by the host immune system. In a mouse osteomyelitis model, Shiono demonstrated that P. acnes infection persisted only in the presence of an implant with complete disappearance in the non-implant group by 28 days [4]. Whereas inoculation of 107 bacteria may cause no clinical infection when injected into a host with a competent immune system, as few as 102 bacteria have been shown to produce significant infections in 95% of subcutaneous implants [1,5]. It is therefore critical to address pathogenic bacteria as early as possible in order to minimize biofilm formation. It is the first 6 hours after implantation that are most decisive [2]. 

For bacterial colonies allowed to persist and form a biofilm (an accumulation of microorganisms embedded in a self-produced polysaccharide matrix), they must first adhere.  It is this biofilm that makes these bacteria highly resistant to antibiotic treatment and the host immune response [1]. Consequently, limiting bacterial adhesion is a necessary course of preventing biofilm and thus infection. Such a strategy may eliminate the risk of infection altogether in conjunction with a healthy immune system as bactericidal surfaces can kill bacteria as they contact the implant surface [2]. 

Deep implant infections are typically classified as primary/early/acute, delayed, or secondary/late. Whereas early and delayed infections have been attributed to bacterial inoculation of the implant at the time of surgery, the etiology of late infections has been thought to be from distant sources spread hematogenously. In 2013, 60% of deep implant related infections were believed to be from direct perioperative implant inoculation [1]. Over the past several years however, this percentage has dramatically increased as many late occurring infections have been shown to be linked to bacteria exposed to the implant at surgery. Of 82 patients who underwent pedicle screw removal with no apparent signs of clinical infection, 54 patients showed loosening of the screws by intraoperative inspection. 41% (22/54) of loose screws were noted to demonstrate positive cultures of one or more bacteria following sonication. Additionally, none of the 28 patients without screw loosening were found to have positive cultures [6]. Chronic implant infection appears to play a role in pedicle screw loosening and pain [7]. 

Latent subclinical infections are often caused by common skin flora such as Cutibacterium acnes (previously Propionibacterium acnes) via an exogenous or direct implant inoculation route at the time of surgery [8]. The diagnosis of bacterial infection is challenging due to biofilm formation, slow-growing organisms, low bacterial loads, and prior antibiotics [9]. Consequently, ineffective treatment has led to a dramatic increase of antibiotic resistance allowing for opportunities to develop novel non-drug approaches to reducing bacterial inoculation related to orthopedic implant infections [10]. 

Strategies are needed to prevent perioperative implant colonization [6]. An ideal strategy for eliminating implant inoculation is to kill the bacteria and prevent its initial adhesion. A bactericidal surface that kills bacteria on contact fits this requirement. Eluting surfaces lose effectiveness as the coating dissociates from the material and may be associated with antibiotic resistance. Permanently attached bactericidal molecules, on the other hand, maintain surface effectiveness and have no propensity to create drug resistant bacteria. 

The ideal implant treatment should be cost-effective, applicable to any geometry implant while maintaining the shape, size, and feel of the implants [2]. 

  1. Song Z, et. al., Prosthesis Infections after Orthopedic Joint Replacement: the Possible Role of Bacterial Biofilms, Orthop Rev 2013 Jun 7; 5(2):e14.
  2. Raphel J, et. al., Multifunctional Coatings to Simultaneously Promote Osseointegration and Prevent Infection of Orthopedic Implants, Biomaterials 2016 Apr; 84:301-314.
  3. Ribeiro M, et. al., Infection of Orthopedic Implants with Emphasis on Bacterial Adhesion Process and Techniques Used in Studying Bacterial-Material Interactions, Biomatter 2012 Oct 1; 2(4): 176-194.
  4. Shiono Y., Delayed Propionibacterium Acnes Surgical Site Infections Occur Only in the Presence of an Implant, Sci Rep, 2016; 6:32758.
  5. Montanaro I, et. al., Scenery of Staphylococcus Implant Infections and Orthopedics, Future Microbiol 2011; 6: 1329-1349.
  6. Ives, James (editor), Microorganisms on Explanted Pedicle Screws Could Be Potential Cause for Spinal Implant Failure, J Neurosurg
  7. Leitner L, et. al., Pedicle Screw Loosening Is Correlated to Chronic Subclinical Deep Implant Infection: a Retrospective Database Analysis, European Spine Journal Apr 2018; 27 (5).
  8. Gisler V, et. al., Late Spinal Implant Infection Caused by Cutibacterium acnes, J Bone Jt Infect 2019; 4(4): 163–166.
  9. Drago L, et. al., The World Association against Infection in Orthopedics and Trauma Procedures for Microbiological Sampling and Processing for Peri-Prosthetic Joint Infections and Other Implant-Related Infections, J Clin Med 2019 Jul; 8(7): 933.
  10. Bingyun Li and Webster Thomas, Bacteria Antibiotic Resistance: New Challenges and Opportunities for Implant Associated Orthopedic Infections, J Ortho Res 2018 Jan; 36(1): 22-32.