Introduction                       

The operative management of periprosthetic infection after total hip arthroplasty (THA) remains a challenge procedure to any arthroplasty surgeon. After primary THA the infection rate is reported usually within a range between 0.5 to 2 %, this however, might increase up to 10 % in the field of revision THA and related implant exchange.1-3 Consequently periprosthetic infections are still a relevant problem, despite modern operative technologies, implants and rigorous perioperative prophylaxis.

While it has been widely accepted that the treatment of a late chronic infection should be obtained by a two staged revision technique, including implantation of a new prosthesis, an own technique by a distinct single staged revision approach, have shown similar good results within the last 30 years.4-6

The overall therapeutic goal in either one or more staged revisions of periprosthetic infections is in general defined by a complete eradication of the infection and further maintenance of the hip joint function.

Both revision techniques and clinical applications should be available depending on the clinical situation, the local set-up, the surgeon’s preference and expertise. In the most frequent scenarios however, implant removal is followed by a defined 6 weeks course of antibiotics and a consequent delayed revision arthroplasty.1,7,8

However, one-stage exchange within the infected THA revision offers certain advantages, as the need for only one operative procedure (if no recurrence), reduced hospitalization time, reduced overall cost and relative improved patient satisfaction.9

In this chapter the authors will describe their clinical management strategy and experience with the one staged approach in the revision of an infected THA. Technically the requirements that provide the basis for the surgical and postoperative success are provided in detail by the intraoperative images.

 

Etiology         and         Classification                 

Principally any periprosthetic infection is a foreign body associated infection and must be clearly differentiated from other bone infections. Where as the interaction between the foreign body and host defence arises, also a direct interaction between the bacterias and the foreign body occurs.10-13 Therefore micro-organisms and foreign materials can induce inflammation as a reaction to tissue injury.

Mostly micro-organisms from human bacterial flora gain access to the surface of the prosthesis during the operative procedure. More than 90% of infections during the first

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year after implantation are due to bacterial contamination during the surgical procedure itself.14 Haematogenous infections are less frequent. In the presence of foreign bodies, a contamination as low as 100 colony-forming units (cfu) is sufficient enough to induce an infection in contrast to 10.000 cfu without foreign material.13 This effect is due to the diminished clearing capacity of phagocytosis by leucocytes in the presence of foreign material.15,16

Total Hip Arthroplasty

 

Furthermore, the bacteria are adhesive to the implant surface by forming a biofilm. This biofilm protects from the host’s defence mechanisms and these sessile bacteria are also highly resistant to antimicrobial agents.11 Furthermore within the biofilm, the minimal inhibitory concentration can be elevated up to the 1000-fold.

The general period between colonisation and clinically detectable infection may last for months, even up to about three years. Signs of infection may occur very late when the bacteria leave the interface, invade surrounding tissue and induce a secondary osteomyelitis. It is important to realize that periprosthetic infection is not only an infection of the prosthetic interface, but also an infection of the surrounding bone and soft tissues.

 

BASIC CLASSIFICATION

1. Infections occurring within the first 3 postoperative weeks should be considered as an

   acute infection.

2. Infections occurring after the third postoperative week are referred as late infections.

Principally an early revision of the acute infected THA might still be possible within a local debridement, soft tissue revision and lavage, including even preserving of the initially implanted prosthesis. A late infection should always be treated with a definite implant removal and further re-implantation of a new prosthesis, if applicable.17-20

 

Diagnosis

 

The early diagnosis of an infection usually establishes with the first symptoms around 4 to 8 days after THA. In the presence of purulent secretion, the diagnosis is obvious. However, any prolonged wound discharge (>10 days), continued soft tissue swelling and induration, or wound dehiscence should be taken seriously, and considered as a possible infection until proven otherwise. Consequently we suggest in those cases in all times a pro-active and aggressive approach by the involved surgeon. If an early infection (within 3 weeks) occurs after patient discharge from the hospital, often superficial wound healing problems, hematomas and seromas are evident – which often correlate with the presence of deep infection of the implant.

This however, is not always obvious and the clinical signs can be more subtle. Laboratory monitoring of C-reactive protein (CRP) is the most useful parameter in this scenario.21 CRP values are highest with a peak on day 2-3 postop, and should return to physiological, preoperative values within 3 weeks. In some few cases, CRP normalization can last up to 6 weeks. As long as those CRP values show a continuing decline, there should be no concern.

Whereas obvious clinical symptoms are the main parameters for periprosthetic infections in its early stages, laboratory and radiological assessments become more important in the late infection scenario. Erythrocyte sedimentation rate (ESR) has a longer lag time than CRP and is probably only useful in the management of patients with rheumatoid arthritis and combined chronically raised CRP levels. ESR and CRP have a specificity and sensitivity of about 90% in periprosthetic infections; while a related leukocytosis is unspecific and rarely present. More recent and sophisticated parameters like Interleukin 6 or Procalcitonin sometimes accelerate an accurate detection of ongoing infections, however are relatively expensive.6,20,22

Clinically the most important parameter in late infection is the presence (or recurrence!) of pain. However typically is an initial pain free interval directly after the primary intervention.

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Serial radiographic comparison can be of value and related bone scans, as scintigramms, are non-specific although highly sensitive. Bone scans have shown to visualize suspicious enhancements for several years following arthroplasty, however can represent bone remodeling and may be misleading.

Management of the Infected Total Hip Prosthesis: The One Staged Approach

 

In our opinion and clinical set, joint aspiration with prolonged culture time of at least 10-14 days is considered mandatory and gold standard for any type of THA and TKA revision.12,13,22-24 This protocol is mandatory for every planned THA revision including late and timely aseptic loosening and obvious implant misplacements. Furthermore it is also done in our set up for every patient with unclear prolonged pain or other unclear limitations after joint replacement.10-13 In any unclear aspiration data arise, a further current recommendation even includes standardized preoperative biopsies.22

Consequently we were able to identify that between 4-7% of all our patients planned for aseptic THA revision have evidence for a low grade infection, without any obvious clinical symptoms as described above.13

 

Preoperative Preparation and Planning for

the      One       Staged       Revision                  

The presence of a positive bacterial culture and respective antibiogramm is absolute mandatory for the one-staged procedure. A cemented fixation using antibiotic loaded acrylic cement (ALAC) is considered to be the treatment of choice in order to achieve a high topic therapeutic level of antibiotic elution from the ALAC.17,25

The principal success of a one staged approach does not only depend on the distinct and complete removal of all hardware material (including cement and restrictors) in combination with the ALAC, furthermore the aggressive and complete debridement of any infected and soft tissues and bone allows for a high success rate. A full synovectomy is extremely important and need to be done routinely. If possible all remaining cement within the femoral canal needs to be removed, including the stopper and other remaining hardware.

 

GENERAL PRE-OPERATIVE PLANNING

 

Anaesthesia

• Clinical and anaesthesiology assessment of the general operative risk

• Adequate quantity of additional donor blood

• In case of long exchange operations preoperative administration of fibrinolysis inhibitors (e.g. Tranexam acid) is recommended.

   

  Radiological Preparation

  Conventional radiographs of the pelvis ap and affected hip oblique, are usually adequate. In severe osseous destruction or hardware migration at the pelvis, a preoperative CT scan might become necessary to allow for proper preoperative planning.

   

  Patient Information – Specific Risks

• Risk of recurrent or new infection – about 10-15%

• Reoperation for haematoma, wound debridement or persistent infection

• Damage to the sciatic nerve

• Recurrent dislocation of the hip joint

• Gluteal insufficiency

• Risk of intra- and postoperative fracture

• Increased risk of aseptic loosening.

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  SURGEON’S PLANNING AND PREPARATION

   

  Choice of Implants and Cement

  Total Hip Arthroplasty

   

  • The surgeon should have distinct knowledge of the implant in situ and be familiar with its removal and disassembly. Occasionally the use of implant-specific instrumentation becomes necessary.

  • Principally a variety of implants must be available, from prolonged revision stems to reinforcement rings or larger metal cages.

  • Inadequate bone stock, possible intraoperative complications as femoral or acetabular fractures, perforations of the cortex, osseous windows and femoral desintegration must be taken into consideration when choosing an appropriate implant.

  • Bone loss is usually significantly more extensive than radiographically evident. Custom made implants with extra long or narrow stems may have to be ordered prior to surgery. The potential need for total femoral replacement implants should also be considered in severe cases.

  • ALAC with additional antibiotics (AB) in powder form to be added intraoperatively should be available in all cases. Invariably at least 1-2 mixes of cement (60-120 g) per femur and also per tibia are required. Large mixing systems and appropriate cement guns are required. In patients with a narrow diaphysis extra narrow nozzles allow for appropriate retrograde cementing technique.

  • The surgeon should know if and which type of ALAC has been used at the primary operation, as resistance to the previously used AB must be expected. Consequently a totally different ALAC should then be considered. In many cases, an industrial pre-manufactured ALAC cement may even be appropriate. As mentioned above, for the success of any one staged procedure, an antibiogramm for the final cement impregnation with further related recommendation for the following postoperative i.v. administration is absolute mandatory.

     

    Operative                    Technique                   

    SKIN INCISION AND DEBRIDEMENT

  • Old scars in the line of the skin incision should be excised. Between two incisions, one should maintain sufficient distance between them. The prior incision from the last operative approach should be used, if possible.

  • Fistulae should be integrated into the skin incision and radically excised to the joint capsule. In cases of increased distances of the fistulae to the lateral or posterior aspects, a separate excision should be used. Methylene blue injections can be helpful in this case. Generally a aggressive debridement is necessary in all onet staged procedures, which should optimally include some en-bloc resection of the affected soft tissues at the femoral and acetabular side (Figs 39.1 to 39.4B).

    Thus a complete resection usually includes larger amounts of soft tissues compared to the two staged approach (Fig. 39.5).

  • If the need for muscular-cutaneous flaps can be anticipated, a plastic surgeon should be available.

  • Biopsy material, preferably 5-6 samples, should be taken as a routine measure from all relevant areas of the operation site for combined microbiological and histological evaluation.14,19,22 Afterwards the defined AB are administered. This commonly comprises a wide spectrum cephalosporin with further AB related the antibiogramm.

     

    IMPLANT REMOVAL AND COMPLETION OF DEBRIDEMENT

  • Removing cemented THA implants themselves is often easier and less invasive than removing cementless components, in particular when these are stemmed and ingrown

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    Management of the Infected Total Hip Prosthesis: The One Staged Approach

     

    Figures 39.2 and 39.3: En-bloc resection around the stem

     

    Figures 39.4A and B: En-bloc resection at the cup

    Figure 39.1: Obvious soft tissue affection of the infected uncemented hip

     

    573

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    Total Hip Arthroplasty

     

    Figure 39.5: The completed soft tissue resection during a one staged approach

     

    Figure 39.6: Narrow straight stems should be used around the stem

     

     

    (Fig. 39.1). However the need to remove all cement and possible restrictors can be time consuming and technically demanding within the one staged approach.

  • In cases of well fixed uncemented components, sometimes cortical windows are required to gain access to the interface. High speed burrs and curved saw blades can aid the removal. However even in experienced hands, occasionally significant destruction and related loss of bone stock can occur.

  • Narrow straight osteotomes with symmetrically coned blades should remove all accessible bone cement or along the uncemented stem (Fig. 39.6).

  • A full range of narrow and wide osteotomes of various thicknesses (Lambotte osteotomes) should be available (Fig. 39.7). By using multiple osteotomes, which are carefully driven along the stem can be gradually wedged/forced out from its cement mantle, which is less destructive than aggressive extraction with the mallet.

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    Management of the Infected Total Hip Prosthesis: The One Staged Approach

     

    Figure 39.7: A full range of narrow and wide osteotomes of various thicknesses (Lambotte osteotomes) should be available

     

     

• Extraction of the implant necessitates special or universal extraction instruments, if available. Thus a universal explant tool has been established in our clinic, that allows for an adequate fixation at the prosthesis cone through mini screw fixation (Figs 39.8 to 39.11).

• Special curved chissels, long rongeurs, curretting instruments, long drills and cement taps are used to remove the cement (Figs 39.12 and 39.13). If necessary a penlight can be used in the deeper femoral canal, if an endofemoral approach is considered.

• General debridement of the affected bone and soft tissues must be as radical as possible. It must include all areas of osteolysis and non-viable bone (Figs 39.14 to 39.17).

• Finalisation of the aggressive debridement often exceeds the amount of resected materials than in a two staged approach (Fig. 39.18)

• Pulsatile lavage should be used throughout the procedure (Fig. 39.19).

• After further extensive lavage, the intramedullary canals are packed with Chlorhexidine soaked swabs (Lavasept) and large Chlorhexidine soaked packs are placed in the wound area, before it is provisionally covered before re-draping.

• The complete surgical team should now re-scrube, while new instruments are used for re-implantation and after complete re-draping.

• A second dose of AB is given after 1.5 hrs operating time or if blood loss at this point exceeds 1 l.

   

  REIMPLANTATION

• We prefer to fill large defects with ALAC , if morsilized allograft has to be used, it should be thoroughly lavaged (pulsatile lavage with hot saline!) and impregnated with antibiotics prior to impaction grafting. However recently we more often adapted to the alternative use of tantalum wedges at the acetabular side. Variations of depth and width of those augments allow for a proper reconstruction of the resulting bone loss, including an excellent biocompatibility and related stiff ness and cellular structure comparable to bone. Consequently a combined fixation of the cement with an all-polyethylene cup becomes possible (Figs 39.20 to 39.22). In cases of severe bone loss and insufficient stability, reinforcement rings might become necessary in addition.

• The antibiotic loaded cement is prepared in the meantime, while it is mandatory to use only suitable antibiotics fulfilling the following criteria’s:

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Total Hip Arthroplasty

 

Figures 39.8 to 39.11: A universal explantation tool has been established in our clinic, that allows for an adequate fixation at the prosthesis cone through mini screw fixation

 

 

 

Figures 39.12 and 39.13: Drills, long ronheurs and curved or retrograde chisels are used to allow for a complete endofemoral approach

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Management of the Infected Total Hip Prosthesis: The One Staged Approach

 

Figures 39.14 to 39.17: General debridement must be as radical as possible. It must include all areas of osteolysis and non-viable bone

 

Figure 39.18: Finalisation of the aggressive debridement often exceeds the amount of resected materials than in a two staged approach

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Total Hip Arthroplasty

 

Figure 39.19: Pulsatile lavage should be used throughout the procedure

 

 

Figures 39.20 to 39.22: A combined fixation of the ALAC cement with an all-polyethylene cup becomes possible, without further need of metal at the cup side

 

 

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• Appropriate AB (antibiogramm, good elusion characteristics from cement,

• Bactericidal (exception Clindamycin)

• Powder form (never use liquid AB)

• Maximum addition of 10%/PMMA powder (e.g. 4 g AB/ 40g PMMA powder

• in MRSA: Vancomycin plus Ofloxacin

Management of the Infected Total Hip Prosthesis: The One Staged Approach

 

• Cave: Antibiotics (e.g. Vancomycin) might change the polymerisation behaviour of the cement, causing acceleration of cement sometimes.

• Generally current principles of cementing techniques for the stem should be applied (Figs 39.23 to 39.25).

• Our wear combination of polyethylene + ceramic has shown reliable results in infected cases (Figs 39.26 and 39.27).

• Postoperatively, i.v. AB are administered according to the microbiologist. Commonly in the one staged approach not more than 14 days are required. The value of prolonged AB given orally after this time period is not proven.

• Progression of CRP levels are the most valuable tool for the postoperative clinical monitoring.

 

Postoperative     Care     and     Rehabilitation            

In comparison to the two or more staged approach, our single approach offers some obvious advantages concerning the postoperative clinical care. The related hospitalisation postoperatively ranges from 12 to 20 days (mean 14), whereas described above the associated

 

 

 

Figures 39.23 to 39.25: Generally current principles of cementing techniques for the stem should be applied

 

 

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Total Hip Arthroplasty

 

Figures 39.26 and 39.27: Our wear combination of polyethylene + ceramic has shown reliable results in infected cases

 

postoperative systemic antibiotic administration is followed for 10-14 days (exception: streptococci). A prolonged administration of intravenous AB for 6 weeks is particular common in the two staged approach, between first and second intervention.26 However the rational for this prolongation has not been 100% clarified in studies, where as known relevant complications might arise with any prolonged AB administration.5,13,27

The physiotherapeutic plan in any one staged septical approach can not be generalised. Due to the variety of soft tissue and bone damaged the extent of infections and further patient specific circumstances, in most cases an individually plan is developed in our set up. Compromises between any necessary immobilisation due to structural damage and attempts for an early mobilisation, especially in the elderly multimorbid patients, have to be made. In any case however, we recommend a mobilisation within the first 8 days postoperatively. Weight bearing should then be adapted to the intraoperative findings and substance defects. Thus a relatively similar mobilisation strategy compared to primary cemented THA allows the patients to fulfil an early rehabilitation process, which should reduce the often associated muscular movement restrictions.

 

Summary

 

The infected THA still remains a devastating complication. Associated difficult surgical management, major morbidity, prolonged hospitalisation and the often limited postoperative mobilisation are often associated with either the one- or two staged surgical approach.28-30 While the two staged approach has become the gold standard in most centers, including the proven high success rate, we have established and followed a strict one staged approach in our clinic since over 30 years in over 85% of our infected THA cases.

Besides the above described possible surgical advantages for the patients, relevant benefit for the patients undergoing a one staged approach, arises from the overall decreased morbidity, by eliminating the need for a second major procedure and related high risk of repeated blood transfusion, associated decreased inpatient stay and quicker mobilisation.9,31 Furthermore it has in general been shown to be the more cost-effective approach, at least within the US medical system.9 A further advantage arises from the reduced duration of postoperative systemic antibiotics, which rarely prolongs more than 14 days in our set up. In summary, the one staged infected THA approach is still insignificantly used within the orthopaedic society, which is also reflected by the limited number of available studies and related results about this technique, although it offers certain obvious advantages. This mainly

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includes the need for only one operation, shorter hospitalization, lower overall cost and high patient satisfaction.

Management of the Infected Total Hip Prosthesis: The One Staged Approach

 

Technically the presence of a positive culture and respective antibiogramm are mandatory preoperatively. A cemented implant fixation using topic antibiotics is treatment of choice on single staged procedures. The essential success of the surgical procedure is related to the experience and existing of a designated microbiologist or infectious disease specialist, who generates a patient specific treatment plan, including specifications of the systemic and topic antibiotic regime. Explantation of the infected implant is followed by an extensive local debridement, including aggressive and complete debridement of all suspicious soft tissues and bone. Consequently implantation of the new implant with cement becomes possible. A defined i.v. and oral systemic antibiotic therapy follows, whereas early mobilisation should be started as soon as possible postoperatively. CRP levels are the most sensitive markers for the clinical follow up. Our Endo-Klinik results after 25 years experience of one staged THA and TKA revisions with a related 80% chance of cure after 15 years, further supports the general philosophy of one staged approaches.5 However the key to success is based on the well defined intra-hospital infrastructure to fulfil the complete pathway of preoperative proper planning, aggressive surgical approach and postoperative specific patient care.

 

Illustrative                      Case                     

A 71 year old female underwent primary THA on her right side in 1998 and additional ipsilateral TKA replacement in 2007. Shortly after TKA she sustained a periprosthetic fracture, treated with (a) ORIF and plating, and, after refracture (b) retrograde nail placement. Early secondary infection occurred locally at the knee side with Enterococcus faecalis, with consequent removal of all local implants and creation of a stable fistula and persistence of systemic antibiotics since 2008. At admission at our institution 2010, she had persisting fistula at right knee with Enterococcus faecalis verification at the right knee, the distal femoral pseudarthrosis and the infected right THA.

The consequent one stage revision included:

1. complete removal of the severely infected and osteomyelitis hosting femur and right THA

2. cemented all polyethylene cup (Mark III, ENDO Model, LINK) with a tantalum wedge

3. implantation of a total femur prosthesis with adapted rotational hinge knee replacement (both LINK, Hamburg)

4. local additional topical antibiotic loaded cement coating of the total femur.

   The overall hospitalisation time with this one staged procedure was 20 days with full weight bearing of the affected leg. No signs of clinical re-infection until now.

    

    

    

   Figure 39.28A: Initial long leg radiographs at admission are visualizing the advanced diagnosis

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   Total Hip Arthroplasty

    

   Figure 39.28B: Obvious loosening of the right cup with Enterococcus faecalis detection in joint aspiration

    

   Figure 39.28C: Distal femoral pseudarthrosis with osseous destruction of the knee after infected TKA and retrograde nail removal

    

    

    

   Figure 39.28D: Complete operative removal of the femur

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   Management of the Infected Total Hip Prosthesis: The One Staged Approach

    

   Figure 39.28E: Explanted femur with obvious signs of chronic infection and osteomyelitis

    

   Figure 39.28F: Reconstruction of the femur with the total femur prosthesis, while the hip was revised with an allpoly cemented cup and tantalum wedge

    

    

    

   Figure 39.28G: Antibiotic loaded topical cement coating of the total femur

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   Figure 39.28H: Postoperative radiographs at time of discharge including the total femur replacement and connected rotational hinge total knee

    

    

    

   Total Hip Arthroplasty

    

   References                       

   1. Ong KL, Kurtz SM, Lau E, Bozic KJ, Berry DJ, Parvizi J. Prosthetic joint infection risk after total hip arthroplasty in the Medicare population. J Arthroplasty 2009;24(6 Suppl):105-9.

   2. Wilson J, Charlett A, Leong G, McDougall C, Duckworth G. Rates of surgical site infection after hip replacement as a hospital performance indicator: analysis of data from the English mandatory surveillance system. Infect Control Hosp Epidemiol 2008;29(3):219-26.

   3. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004;351(16): 1645-54.

   4. Kordelle J, Frommelt L, Kluber D, Seemann K. Results of one-stage endoprosthesis revision in periprosthetic infection cause by methicillin-resistant Staphylococcus aureus. Z Orthop Ihre Grenzgeb 2000;138(3):240-4.

   5. Siegel A, Frommelt L, Runde W. Therapy of bacterial knee joint infection by radical synovectomy and implantation of a cemented stabilized knee joint endoprosthesis. Chirurg 2000;71(11):1385-91.

   6. Steinbrink K, Frommelt L. Treatment of periprosthetic infection of the hip using one-stage exchange surgery. Orthopade 1995;24(4):335-43.

   7. Jackson WO, Schmalzried TP. Limited role of direct exchange arthroplasty in the treatment of infected total hip replacements. Clin Orthop Relat Res 2000;381:101-5.

   8. Winkler H. Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft. Int J Med Sci 2009;6(5):247-52.

   9. Buechel FF. The infected total knee arthroplasty: just when you thought it was over. J Arthroplasty 2004;19(4 Suppl 1):51-55.

   10. Costerton JW, Stewart PS. Battling biofilms. Sci Am 2001;285(1):74-81.

   11. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999;284(5418):1318-22.

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   12. Frommelt L. Aspiration of joint fluid for detection of the pathogen in periprosthetic infection. Orthopade 2008;37(10):1027-34; quiz 1035-26.

   13. Frommelt L. Diagnosis and treatment of foreign-body-associated infection in orthopaedic surgery. Orthopade 2009.

   14. Atkins BL, Bowler IC. The diagnosis of large joint sepsis. J Hosp Infect 1998;40(4):263-74.

       Management of the Infected Total Hip Prosthesis: The One Staged Approach

        

   15. Elek SD, Conen PE. The virulence of Staphylococcus pyogenes for man; a study of the problems of wound infection. Br J Exp Pathol 1957;38(6):573-86.

   16. Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J Clin Invest 1984;73(4):1191-1200.

   17. Hanssen AD. Managing the infected knee: as good as it gets. J Arthroplasty 2002;17(4 Suppl 1): 98-101.

   18. Kriegsmann J, Hopf T, Jacobs D, et al. Applications of molecular pathology in the diagnosis of joint infections. Orthopade 2009;38(6):531-8.

   19. Spangehl MJ, Masri BA, O’Connell JX, Duncan CP. Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am 1999;81(5):672-83.

   20. Trampuz A, Zimmerli W. New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Investig Drugs 2005;6(2):185-90.

   21. Kordelle J, Klett R, Stahl U, Hossain H, Schleicher I, Haas H. Infection diagnosis after knee-TEP-implantation. Z Orthop Ihre Grenzgeb 2004;142(3):337-43.

   22. Fink B, Makowiak C, Fuerst M, Berger I, Schafer P, Frommelt L. The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements. J Bone Joint Surg Br 2008;90(7):874-8.

   23. Frommelt L. Guidelines on antimicrobial therapy in situations of periprosthetic THR infection. Orthopade 2004;33(7):822-8.

   24. Schafer P, Fink B, Sandow D, Margull A, Berger I, Frommelt L. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis 2008;47(11):1403-9.

   25. Hanssen AD, Rand JA, Osmon DR. Treatment of the infected total knee arthroplasty with insertion of another prosthesis. The effect of antibiotic-impregnated bone cement. Clin Orthop Relat Res 1994;309:44-55.

   26. Goldman RT, Scuderi GR, Insall JN. 2-stage reimplantation for infected total knee replacement. Clin Orthop Relat Res 1996;331:118-24.

   27. Siegel A, Frommelt L, Runde W, Engelbrecht E. Primary arthroplasty of infected hips and knees in special cases using antibiotic-loaded bone-cement for fixation. J Arthroplasty 2001;16(8 Suppl 1):145-9.

   28. Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill JJ, Parvizi J. Irrigation and debridement in the management of prosthetic joint infection: traditional indications revisited. J Arthroplasty 2010;25(7):1022-7.

   29. Cui Q, Mihalko WM, Shields JS, Ries M, Saleh KJ. Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty. J Bone Joint Surg Am 2007;89(4):871-82.

   30. Kraay MJ, Goldberg VM, Fitzgerald SJ, Salata MJ. Cementless two-staged total hip arthroplasty for deep periprosthetic infection. Clin Orthop Relat Res 2005;441:243-9.

   31. Pagnano M, Cushner FD, Hansen A, Scuderi GR, Scott WN. Blood management in two-stage revision knee arthroplasty for deep prosthetic infection. Clin Orthop Relat Res 1999;367:238-42