**4. Bacteria responsible for arthroplasty associated infection**

A broad range of bacterial species have been isolated in cases of septic arthritis and osteomyelitis[26]. Pathogens cultured from septic joints include S. aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, as well as Salmonella, Neisseria, Aerobacter, and Bacteroides species[4,24]. Staphylococcus and Streptococcus spp., Haemophilusinfluenzae, E. coli, P. aeruginosa, Salmonella and Mycobacterium spp. are all potential causes of osteomyelitis[7,10,27].

Fig. 2. Causes of Infection Associated with Prosthetic Joints

A small number of often otherwise nonvirulent bacteria contaminate the implant during surgery and persist as a biofilm despite a functional immune system and antimicrobial treatment. Commonly isolated microorganisms are shown. Unusual organisms that can also

joint) and fever are common. Chronic infection generally has a more subtle presentation, with pain alone, and it is often accompanied by loosening of the prosthesis at the bone–

Reactive arthritis is a postinfectious complication with no need of presence for viable pathogens in the joint. While reactive arthritis often simultaneously affect several joints, the presence of polyarthritic types of non reactive arthritis occur infrequently and then mostly

Among joint infections, the knee is the most frequent localization than others. Infection occurs in 0.8 to 1.9% of knee arthroplasties[12-14]and 0.3 to 1.7% of hip arthroplasties[14-16]. However, hip joint infections are aggravated by the fact that they can exist over a long time with only poor symptoms. Basically, there are no differences in the bacterial spectrum

A broad range of bacterial species have been isolated in cases of septic arthritis and osteomyelitis[26]. Pathogens cultured from septic joints include S. aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, as well as Salmonella, Neisseria, Aerobacter, and Bacteroides species[4,24]. Staphylococcus and Streptococcus spp., Haemophilusinfluenzae, E. coli, P. aeruginosa, Salmonella and Mycobacterium spp. are all potential causes of osteomyelitis[7,10,27].

A small number of often otherwise nonvirulent bacteria contaminate the implant during surgery and persist as a biofilm despite a functional immune system and antimicrobial treatment. Commonly isolated microorganisms are shown. Unusual organisms that can also

cement interface and sometimes by sinus tract formation with discharge.

**4. Bacteria responsible for arthroplasty associated infection** 

Fig. 2. Causes of Infection Associated with Prosthetic Joints

as a result of several bacteriaemic phases.

among large joints.

cause infection include (but are not limited to) Actinomyces israelii, Aspergillus fumigatus, Histoplasma capsulatum, Sporothrix schenckii, Mycoplasma hominis, Tropheryma whipplei, and mycobacterium (including tuberculosis), brucella, candida, corynebacterium, granulicatella, and abiotrophia species.

Some bacteria have preferences for certain infection routes and patterns. Infections not related to injuries or medical interventions (e.g. intraarticular puncture, joint replacement) are mostly resulting from often physiologic bacteriaemic periods.

S. aureus is the most commonly identified pathogen both in septic arthritis and osteomyelitis, by a substantial margin, regardless of type or route of infection [3,7,28]. Staphylococci (S. aureus and coagulase-negative staphylococcus species) account for more than half of cases of prosthetic-hip and prosthetic-knee infection[29](Fig. 2). Other bacteria


Table 2. Bacteria responsible for (hip) joint infections

Staphylococcus Infection Associated with Arthroplasty 465

prevalence of both fnbA and fnbB genes, as opposed to just one of the two, to be significantly higher in invasive isolates than in 'carriage' strains in a panel of 163 strains, which included septic arthritis and osteomyelitis isolates. Genes encoding Panton-Valentine leukocidin were found to be present in 59 of 89 S. aureus isolates from cases of acute haematogenous osteomyelitis. The presence of pvl genes is associated with an increased risk of severe infection requiring intensive care, bacteremia and more severe systemic inflammation [39,40]. However, one of the problems with the above studies is that it is unclear how representative these strain collections are of those isolates carried in other

Strain typing studies of S. aureus, using multilocus sequence typing (MLST) and comparative genomic microarray hybridizations have so far failed to identify any specific clonal lineages associated with invasive disease. However, these studies did not use a collection of isolates from specific invasive diseases and therefore do not rule out the possibility that specific lineages or genes are associated with specific types of infection, such

To date, the only genome comparison study relevant to S. aureus bone infections has been done using comparative genome microarray hybridisations of the S. aureus UAMS-1 strain, isolated from an osteomyelitis patient, with a range of genome sequenced strains[41]. These authors found variations in the complement of adhesin, toxin, exoenzyme and regulatory genes. Although it is not possible to draw general conclusions about association with bone infection from characterisation of a single strain, the presence of fnbA, but not fnbB or the bone sialoprotein-binding gene bbp, in UAMS-1 suggest that fnbB and bbp are dispensable for bone infection, at least in certain genetic backgrounds. Thus at this juncture there is a lack of evidence to support or disprove an association between specific S. aureus lineages or

In terrestrial vertebrates mature bone is made up of dense surface plates of bone, known as the cortices, and within these is a network of bone struts oriented to oppose loading forces, known as trabecular bone. Trabecular bone is typically replaced every 3–4 years, with the denser cortical bone taking over a decade to replace in adults. This process of continual remodelling is required to remove old bone and microfractures to ensure bone integrity and mineral homeostasis. The skeleton is a dynamic organ system, in a state of perpetual turnover which is continually remodelled by the actions of two cell types, osteoblasts and

Osteoblasts are responsible for the deposition of bone matrix; they are found on bone surfaces and are derived from mesenchymal steoprogenitor cells. These cells secrete osteoid, a mixture of bone matrix proteins primarily made up of type I collagen (over 90%), proteoglycans such as decorin and biglycan, glycoproteins such as fibronectin, osteonectin and tenascin-C, osteopontin, osteocalcin and bone sialoprotein, oriented along stress lines. Osteoblasts are also thought to facilitate the mineralization of bone matrix, whereby hydroxyapatite, [Ca3(PO4)2]3·Ca[OH]2, crystals form, making up around 90% of bone matrix. It is thought that 'nucleators' are required to instigate mineralisation, and phosphate-containing matrix proteins like bone sialoprotein and osteopontin are likely to play such a role. Osteoblasts also produce tissue nonspecific alkaline phosphatase (TNAP) which cleaves phosphate esters to liberate free inorganic phosphate, which is key to the

establishments and regions across the world, since strain typing was not reported.

specific genomic features and the pathogenesis of bone infections.

as osteomyelitis or septic arthritis.

**5.2 Bone as a target organ** 

process of mineralisation[42].

osteoclasts.

and fungi cause the remainder of cases[30,31]. Moreover, Staphylococcus aureus has the dominance in acute septic arthritis, and is particularly common in patients with rheumatoid arthritis[32]while coagulase -negative staphylococci can be found mainly in periprosthetic infections and after diagnostic arthroscopies.

 Other gram-positive bacteria as causative agents for hip joint infections are streptococci, especially Streptococcus pyogenes, Enterococcus faecalis and Corynebacteria species. Propionibacterium acnes is a common cause of infection associated with shoulder arthroplasty[33].

A large number of different gram-negative rods act as infectious agents on joints. The group of enterobacteria contains a broad spectrum of pathogens. Salmonella enterica, Shigella species, and Yersinia species are classically described as pathogens for purulent and reactive forms of arthritis. Pseudomonas aeruginosa can be found more often in predisposed patients (e.g. diabetics). In otherwise healthy people it is associated with iatrogenic modes of infection during diagnostic procedures.

Campylobacter species, however, are classic agents of reactive arthritis, as well as the obligate intracellular bacteria Chlamydia trachomatis, Mycoplasma pneumoniae, and Ureaplasma urealyticum. From the spirochaetales only Borrelia burgdorferi sensu lato is relevant. Less commonly identified organisms for joint infections often accompanied with osteitis or osteomyelitis are Brucella species and Mycobacterium tuberculosis.

Up to 20% of cases are polymicrobial, most commonly involving methicillin -resistant S. aureus (MRSA) or anaerobes, such as Bacteroides fragilis[34]. Approximately 7% of cases are culture-negative, often in the context of previous antimicrobial therapy[35].

An overview is shown in Table 2[8].

Infection with virulent organisms (e.g., S. aureus and gram-negative bacilli) inoculated at implantation is typically manifested as acute infection in the first 3 months (or, with hematogenous seeding of the implant, at any time) after surgery, whereas infection with less virulent organisms (e.g., coagulase-negative staphylococci and P. acnes) is more often manifested as chronic infection several months (or years) postoperatively.
