Indications for two over a single stage revision procedure in management of PJI include:

1. Patients with systemic manifestations of infection (sepsis);
2. Obvious clinical signs of infection but no organism has been identified;
3. Preoperative cultures identifying difficult to treat and antibiotic-resistant organisms;
4. Presence of a sinus tract;
5. Inadequate or non-viable soft tissue coverage.

It is our routine practice to perform aspiration of the affected joint before surgery to identify the causative organism [6]. In cases where the infecting organism and its antibiotic sensitivity profile are identified pre-operatively, the antibiotics are adjusted accordingly. In all other cases with no identified growth, broad spectrum antibiotics such as vancomycin and an aminoglycoside are added to the cement mixture as they cover most organisms [6, 20].

Aspiration is ideally performed under strict aseptic conditions after having discontinued all antibiotics for duration of at least 4 weeks. Samples should be placed in aerobic/anaerobic blood culture bottles as well as universal containers. In cases where infection is suspected, arthroscopic biopsy is carried out with a minimum of six samples taken from the prosthetic surfaces and synovium [6].

Sensitivity of pre-operative aspiration and/or tissue biopsy in diagnosing infected TKA has been reported as 12% -100% [31-35]. Meermans et al. [36] performed a prospective study of 120 patients who underwent aspiration and biopsy for suspected joint infection (64 with THAs and 56 with TKAs) . The sensitivity reported was 83% for aspiration, 79% for biopsy, and 90% for the combination of both techniques. The specificity was 100% for aspiration and biopsy and the combination. The overall accuracy was 84%, 81%, and 90%, respectively [36]. They inferred that routine aspiration must be followed by a biopsy in the work up of septic joints.

Cement spacers can be classified as articulating (dynamic) or nonarticulating (static), pre-fabricated or custom-made. The use of a static spacer block makes exposure at reimplantation difficult due to quadriceps contracture. There is also a risk of additional bone loss attributable to migration of the spacer block [18, 24, 40].

Articulating spacers avoid prolonged immobilization of the joint and prevents soft tissue contractures by permitting range of movement and partial weight bearing [18, 19, 40, 41]. Improved patient mobility preserves the soft tissue envelope that is crucial during the reimplantation procedure.

The spacer also helps maintain the native tension of the collaterals. This serves to preserve and identify planes better during subsequent revision, avoiding further soft tissue damage and aiding recovery. After thorough debridement, an antibiotic-laden cement spacer is then implanted. Commonly used spacers are Prostheses of Antibiotic-Loaded Acrylic Cement (PROSTALAC) articulating spacers to which 3 g of vancomycin and 2 g of gentamicin per sachet of Palacos R cement (Schering Plough Ltd, Labo nv, Belgium) is added. The objective is to deliver a high concentration of local broad spectrum antibiotics against most common causative pathogens prior to culture results. The antibiotics are also adjusted when preoperative sensitivity pattern of the microorganisms is known. A five-day course of intravenous teicoplanin or vancomycin is also continued post-operatively, by which time microbiological sensitivities are available.

Biring et al. [42] in their study of 99 patients treated with PROSTALAC articulating hip spacers (DePuy, Warsaw, Indiana) have quoted long-term infection control rate of 89% at a mean follow up of 12 years (range 10-15 years). Gooding et al. [43] reported 98% infection control rate (113 of 115 infected TKRs) using the PROSTALAC knee spacers (DePuy, Warsaw, Indiana) at a minimum of 5 years follow up. Van Thiel et al. [41] retrospectively reviewed post-operative function and control of infection in 60 patients using an articulating antibiotic spacer made intra-operatively from prefabricated silicone moulds. Seven patients (12%) developed recurrent infection, and one spacer (femoral component) fractured but did not require specific treatment. No bone loss was identified between stages. The mean Knee Society score improved from 53 preoperatively to 79 at a mean follow-up of 35 months and the mean flexion improved from 90.6° to 101.3°. This study illustrated control of deep infection in 88% of patients while preserving knee motion [41]. Various studies [19, 44] have found a significant increase in knee society function scores in patients with dynamic spacers but no difference in pain scores. Brunnekreef et al. [45] reported better and faster recovery of knee function with the use of dynamic spacers resulting in shorter operation times. Garg et al. [46] suggested that static spacers not only reduce the range of motion of the knee joint but can also cause difficulty in exposure during second stage with the potential for additional bone loss due to scarring of the capsule and quadriceps muscle. Faschingbauer et al. [47] enlisted complications associated with using antibiotic loaded spacers in 138 patients. 27 patients (19.6%) developed complications including spacer fractures in 12 cases (8.7%), dislocation in 12 cases (8.7%), one periprosthetic femoral fracture (0.7%) with a spacer in situ, one dislocation with a simultaneous spacer fracture (0.7%), and one protrusion into the pelvis.

Intravenous (IV) antibiotic therapy for 4-6 weeks with subsequent cessation of antibiotics for 2-8 weeks prior to reimplantation is most commonly employed regimen and has resulted in overall good infection control rates [27, 48]. Best results are obtained in cases where the pathogen is not resistant and systemic antibiotics are administered simultaneously [2, 49]. Studies have suggested that prolonged time intervals result in suboptimal restoration of patient function and eradication of infection. However, in one study, there was no difference in functional outcomes between patients who underwent two-stage exchange procedure with more than 6 month interval between resection and reimplantation and those who had reimplantation within 6 months of resection [50].

At our institution, it is common practice to start a course of intravenous antibiotics, usually teicoplanin until the sensitivity pattern of the culture samples are known. The results are discussed in the multidisciplinary meeting, and the antibiotics are modified accordingly. Our patients receive antibiotics for at least six weeks following which the antibiotics are stopped for two weeks prior to the second stage to foresee the patient’s response. We perform routine aspiration of the involved joint in all cases prior to revision surgery. Stopping the antibiotics provides another opportunity to grow any residual microorganisms at the time of reimplantation. The decision to proceed with prosthesis implantation is determined by clinical evaluation, resolution of blood markers and a negative joint aspirate. Any suspicion of residual infection mandates redoing the first stage with debridement and placement of a new spacer.

A normal C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) alone do not guarantee eradication of infection, particularly with coagulase negative staphylococcal infections. Kusuma et al. [51] in a recent study suggested that synovial white cell count is the most accurate indicator of control of infection, and although the levels of inflammatory markers tend to fall with control of infection, they do not show a clear pattern.

The role of reimplantation cultures as well as intraoperative frozen section in the two-stage revision arthroplasty remains controversial. Banit et al. [63] prospectively compared the accuracy of intraoperative positive frozen section (>10 polymorphonuclear leukocytes per high power field) with intraoperative cultures in 121 revision hip and knee arthroplasty. They found that frozen sections had 67% sensitivity and 93% specificity in detecting infection with 67% positive predictive value and 93% negative predictive value. Low sensitivity of frozen sections was similarly reported in other studies [39, 64]. This could be attributed to sampling errors, which emphasizes the importance of wide sampling [64]. Therefore, the reliability of frozen section as a diagnostic tool for infection in reimplantation procedures remains questionable.

Positive cultures have varied from 0% to 28% at reimplantation [29, 65-67]. Many a times it has been reported that the microbes cultured at reimplantation were different from those cultured at excision. Hart et al. [28] reviewed 48 patients who underwent two-stage revision TKAs. At the time of second-stage surgery, 11 patients (23%) had positive cultures and two of those developed recurrent infection. The cultured microbe was different in seven cases and rest four cases revealed persistent coagulase-negative staphylococcus. Out of the remaining 37 patients with negative cultures, four developed recurrent infection. Authors concluded that the possible reason for growth of different organisms during the second stage could be due to sample contamination during the first surgery.

Puhto et al. [68] in their series of 107 cases reported that the reimplantation microbiology was available in 90.7% of cases, and the samples were positive in 5.2%. Only one of the 5 samples that were reported positive had the same organism isolated at the time of implant excision (Candida albicans) and the treatment failed in this case. The other four patients were treated as having an acute postoperative PJI with a short-course of antibiotics and prosthesis retention. Eighty percent of patients with positive reimplantation samples were cured of infection as compared to 96% with negative reimplantation samples.

Bejon et al. [65] in a series of 152 cases found that routine cultures sent at reimplantation were positive in 21 patients (14%). Reimplantation cultures were frequently more positive in knees than in hips (21% vs. 6%). The same organism was isolated at both excision and reimplantation in 4 cases and different in10 cases. Moreover, seven cases reported positive reimplantation cultures following previous negative cultures. There was no evidence that positive reimplantation cultures were associated with worse outcome. Contrary to many studies that recommend second stage after a trial of antibiotic free period and testing, the authors suggested that reimplantation may be considered without an antibiotic-free period, with additional antibiotic prophylaxis before reimplantation. A limited antibiotic course may also be prescribed when reimplantation cultures are positive in the absence of clinical signs of ongoing infection [65].

There is sparse data on studies that compare patient reported outcome measures (PROMs) in single versus two-stage revision for infection. Baker et al. [69] compared patient outcome scores (Oxford knee scores, Euroqol-5D) of single versus two stage septic knee revisions in 195 patients. They found no differences in post-operative knee scores, general health perception or satisfaction between the study groups. Hence, the recommendation was that decision making should take into account other factors including infection control rates when comparing both groups.