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Biofilm on bone repair devices

S.S. Dastgheyb1'2, M. Otto2, N.J. Hickok1

'Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia,

PA, United States; 2National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, United States

I ntroduction

Orthopedic procedures are mobility-restoring procedures that have significantly added to the health and longevity of the aging population. Antibiotic prophylaxis, rapid surgical times, and stringent sterile techniques have markedly lowered infection rates (Kurtz et al., 2012; Norden, 1991). However, because of the increasing frequency of these procedures, the number of patients suffering from the devastating consequences of an orthopedic infection will continue to increase. Those with infections are treated at the least, with a prolonged course of antibiotics. Further surgeries are often necessary, and in recalcitrant cases, loss of limb and even death may result (Aggarwal et al., 2013a). The purpose of this chapter is to review the current state of understanding of these infections and to highlight new areas that may yield important insight into treatments of these life-altering infections.

When intractable joint or back pain and/or trauma is present, surgical procedures may be required for joint replacements or placement of spinal stabilization hardware. The frequency of infection associated with these procedures depends on the surgical site, the procedure, the duration of the procedure and the health status of the patient. For instance, the infection rate for transcutaneous pins that are used to stabilize fractures is 2-30% (Masse et al., 2000; De Bastiani et al., 1986; Thakur and Patankar, 1991; Schroder et al., 1986), spinal surgeries under the most stringent conditions still have a 1-4% infection rate (Hedrick et al., 2006; Mankin et al., 2005a; Weinstein et al., 2000), and depending on the center, infection rates for joint replacements can be as high as 1-2%, although high throughput centers tend to maintain rates below 1% (Cierny and DiPasquale, 2002; Duggan et al., 2001; Pulido et al., 2008; Parvizi, 2013). Finally, when allograft bone is used to replace bone in a defect, infection can exceed 11% (Mankin et al., 2005a; Muscolo et al., 2005). After devastating trauma, such as blast injuries, infection rates can surpass 30-50%, due to the forcible contamination with environmental material and due to the immune suppression that accompanies such injuries (Meadows et al., 1993; Mody et al., 2009; Tintle et al., 2011).

How do infections initiate? Despite the use of clean room techniques, space suits, negative air pressure and stringent sterile procedures, orthopedic infections occur and are thought to predominantly arise due to the inevitable contamination that can occur in the presence of open and exposed tissue (Hedrick et al., 2006; Panahi et al., 2012; Alijanipour et al., 2014; Erichsen Andersson et al., 2014). Unfortunately, bacterial

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colonization is facilitated in the presence of an implant—without an implant, more than 104 bacteria may be required to establish infection, whereas in the presence of an implant, as few as 10-100 can seed an infection (Zimmerli and Sendi, 2011; Zaat et al., 2010; Elek and Conen, 1957). The source of bacteria is thought to be contamination during prolonged surgical times, hematogenous spread from other infected sites in the body, environmental contamination during severe trauma or recurrence of previous infections that have occurred in the bone environment and which reestablish in the presence of an implant (Hedrick et al., 2006; Panahi et al., 2012).

Implant infections, while occurring infrequently, pose special problems because of the relative hypoxia of the joint and the intervertebral disc, and the general poor penetrance of antibiotic into bone. In the presence of an implant, whether comprised of allograft bone (for bone augmentation or bone replacement), metal stabilization hardware (spinal fixation and fracture fixation), screws, or joint replacement hardware, these difficulties are exacerbated (Alijanipour et al., 2014; Darouiche, 2003).

In the case of trauma, the nature of the injury itself provides the ingress for environmental contaminants, which will encompass a wide range of pathogens. Because of this sometimes massive contamination, such wounds often undergo extended lavage and antibiotic treatment before the placement of hardware to try to avoid bacterial colonization of bone replacements and/or bone hardware. To lessen the severity of these infections, it will be necessary both to better understand the genesis of the infection at the implant site and to design new, antiinfective hardware that minimize the need for the prolonged antibiotic treatments.

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