Orthopaedic biofilm infections

Abstract

A recent paradigm shift in microbiology affects orthopaedic surgery and most other medical and dental disciplines because more than 65% of bacterial infections treated by clinicians in the developed world are now known to be caused by organisms growing in biofilms. These slime-enclosed communities of bacteria are inherently resistant to host defenses and to conventional antibacterial therapy, and these device-related and other chronic bacterial infections are unaffected by the vaccines and antibiotics that have virtually eliminated acute infections caused by planktonic (floating) bacteria. We examine the lessons that can be learned, within this biofilm paradigm, by the study of problems (e.g. non-culturability) shared by all biofilm infections and by the study of new therapeutic options aimed specifically at sessile bacteria in biofilms. Orthopaedic surgery has deduced some of the therapeutic strategies based on assiduous attention to patient outcomes, but much can still be learned by attention to modern research in related disciplines in medicine and dentistry. These perceptions will lead to practical improvements in the detection, management, and treatment of infections in orthopaedic surgery.

Figure 1

Scanning electron micrograph (SEM) of spherical cells of Staphylococcus aureus in a biofilm formed on an endocardial pacemaker in a patient with a bacteremia secondary to an elbow injury. Note the negative impressions (arrow) of these cells in the slimy matrix within which this thick biofilm was enclosed.

Figure 2

Transmission electron micrograph (TEM) of the biofilm formed in the femur of a rabbit infected with Staphylococcus aureus, in an animal model in which a surgical nail was inserted to compromise the bone. Note the extent to which the sessile bacteria in this extensive community are surrounded by electron dense matrix material.

Figure 3

Biofilm clusters of live bacterial cocci (yellow), identified as S. aureus from reverse transcriptase PCR (RT-PCR) analysis, associated with an infected total elbow arthroplasty. The nuclei of host cells are stained red. Specimens were rinsed and observed under fully hydrated conditions demonstrating that the cell clusters were coherent and strongly adhered to the cement and surrounding tissue. (A) Biofilm clusters (representative cluster shown by arrow) associated with tobramycin-impregnated cement (blue) used as a spacer. (B) Biofilm clusters (arrow) were also associated with reactive tissue and aspirate associated with the cement spacer. Diffuse green staining between the cocci suggests the presence of extracellular DNA (eDNA) in the biofilm slime matrix. Preoperative aspirates were culture negative.

Figure 4

Scanning electron micrograph of a single species biofilm that formed in the mandible of a patient, secondary to a tooth extraction, and persisted for longer than 4 years in spite of aggressive antibiotic therapy. Note the intrusion of human phagocytes into the biofilm (arrows), and the very extensive ramifying network of fine nanowires connecting the cells to each other.

Figure 5

Scanning electron micrograph of mandibular bone from a patient with osteonecrosis secondary to the use of bisphosphonates. Note that very large spaces within the bone (bottom left) are filled with bacterial biofilms, whose fine structure and morphology can be clearly discerned in the main image, and that as much as 50% of the volume of the bone is occupied by these microbial communities.

Figure 6

This illustration shows the ”towers” and “mushrooms” whose complex structures and persistent water channels suggested that some form of cell-cell signaling must be involved in the development of biofilms. This perception led to the discovery of the signals that control this process and to the notion that signal analogues can be used to block biofilm formation (Reproduced with permission from Center for Biofilm Engineering).