**2. Identification of infected implants: The need for microbiological testing**

### **2.1 Epidemiology**

Periprosthetic joint infections are a feared complication of hip and knee arthroplasty. Infection is supposed to be the underlying cause in about 15% of hip revision arthroplasties and 25% of knee revision arthroplasties (Bozic et al., 2009, 2010). Depending on the onset of infection after the primary implantation, periprosthetic infections have been defined as "early" (up to 3 months), "delayed" (3-24 months), and "late" (more than 24 months) after surgery (Zimmerli et al., 2004). However, a different classification makes more sense from the therapeutic point of view. According to this, infections which occur within 4 weeks after arthroplasty implantation are recognized as "early". These are most often caused by highly virulent organisms (e. g. *Staphylococcus aureus*) acquired during or shortly after implantation and can be treated with the prospect of survival of the implant. In contrast, infections which become manifest after more than 4 weeks ("late" infections) require removal of the

Infections in Hip and Knee Arthroplasty:

**2.3.1 Blood laboratory markers** 

patient assessment for arthroplasty infection.

**2.3.2 Microscopic detection of inflammatory cells** 

Challenges to and Chances for the Microbiological Laboratory 441

(Virolainen et al., 2002). Nuclear imaging techniques used to detect periprosthetic inflammation are generally regarded as optional tests which may be of use if the diagnosis cannot be established otherwise, but they are not recommended for routine application (Della Valle et al., 2010). In contrast, the following procedures do play important roles in

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are the parameters most widely used for preoperative evaluation of patients with suspected arthroplasty infection. While sensitivity is mostly high, specificity is limited, especially in patients with systemic inflammatory diseases (e. g., rheumatoid arthritis) (Bottner et al., 2007; Della Valle et al., 2007; Fink et al., 2008; Greidanus et al., 2007; Kamme & Lindberg, 1981). Nevertheless, from the studies with reliable data the AAOS strongly recommends testing of both ESR and

Other inflammation markers (interleukin 6, procalcitonin, tumor necrosis factor ) are evaluated increasingly for periprosthetic infections, but at present there seems to be no advantage over CRP testing (Berbari et al., 2010; Bottner et al., 2007; Di Cesare et al., 2005).

**Joint aspiration fluid.** Total and differential white blood cell counts in synovial fluid are routinely determined in many settings. Some studies of knee patients have reported that total leukocyte counts or neutrophils percentages which exceed a certain cutoff level are highly indicative of arthroplasty infection. However, the thresholds differ considerably

In contrast, there are less data available for hip patients because aspiration of this joint is more prone to complications and is therefore only recommended if there is substantial clinical or laboratory evidence for infection (Della Valle et al., 2010; Schinsky et al., 2008). **Frozen tissue sections.** Neutrophils are the predominant histomorphologic factor in periprosthetic infection (Krenn et al., 2011; Morawietz et al., 2006). As a consequence, the histologic diagnosis of probable infections is based on the tissue neutrophil concentration, as defined by i) the number of neutrophils in a high-power (400x) microscopic field, and ii) the minimum number of fields (usually 10) containing that concentration of neutrophils. The available studies report 5 or 10 neutrophils per high-power field as suitable thresholds for diagnosis of arthroplasty infection (Banit et al., 2002; Della Valle et al., 2007; Fehring & McAlister, 1994; Fink et al., 2008; Frances Borrego et al., 2007; Ko et al., 2005; Lonner et al., 1996; Nunez et al., 2007; Schinsky et al., 2008). Patients with inflammatory arthropathy, which often display tissue infiltration by neutrophils in the absence of infection, were excluded in some of these investigations (Fehring & McAlister, 1994; Ko et al., 2005; Pandey et al., 1999; Schinsky et al., 2008). However, all in all there is not enough information to

Despite the considerable advances in recent years with respect to the histomorphologic characterization of periprosthetic infections, it is not possible to treat affected patients sufficiently unless the causative microorganisms are identified precisely. Thus, customized local and systemic antibiotic therapy of a known infectious agent is inherently superior to calculated therapy because treatment failure arising from antibiotic resistance can be

between studies (Della Valle et al., 2007; Ghanem et al., 2008; Trampuz et al., 2004).

enable a clear-cut preference of the lower or the higher threshold.

avoided (Bejon et al., 2010).

CRP in all patients assessed for arthroplasty infection (Della Valle et al., 2010).

prosthesis. Late infections are low-grade infections due to less virulent agents belonging to the normal skin flora (e. g. coagulase-negative staphylococci, *Propionibacterium* species, coryneform bacteria), which are mostly also attained during the operation procedure or are infections which result from hematogenous spreading from remote sites (Cui et al., 2007; Hanssen & Osmon, 2002; Virolainen et al., 2002).
