What Metrics Can Be Used to Determine the Optimal Timing of Reimplantation in Patients Who Have Undergone Resection Arthroplasty as Part of a Two-Stage Exchange for Infected Total Ankle Arthroplasty (TAA)?

Rationale

Infected total ankle arthroplasty (TAA) is a serious complication that is thought to occur in as many as 5% of patients.^6,16 Management of infected TAA often requires operative intervention that includes removal of the prosthesis, local and systemic antibiotic treatment, and subsequent reimplantation in a select group of patients. One of the most challenging questions pertains to optimal timing of reimplantation. There is little in the literature regarding the optimal treatment of an infected TAA. Most of the available literature has limitations, including low numbers of patients, short duration of follow-up, and so on.^6,9,14,16,21

There are a number of publications related to patients with infected TAA who underwent 2-stage exchange arthroplasty. Patton et al ¹⁴ reported on 29 of 966 cases (3.2%) of infected TAA. Among the infected TAA, 13 patients underwent 2-stage exchange arthroplasty and antibiotic spacer placement. Although infection type and operative cultures were listed, no specific recommendations on timing of reimplantation were made. Similarly, Lee et al ⁹ omitted data regarding timing of reimplantation but reported 1 case of deep infection out of 50 TAAs (2%) that required implant removal, antibiotic-impregnated spacer placement, and later revision TAA. Thoroughly outlining the timeline, Young et al ²¹ detailed a case report of a 2-stage TAA revision. Irrigation and debridement (cefazolin 1 g diluted in 1 L 0.9% saline) and antibiotic cement spacer (80 g of polymethylmethacrylate impregnated with 2 g gentamicin) placement was implemented. The blood cultures and intraoperative bone and tissue cultures in the latter infected case isolated Streptococcus mitis. As a result, a 6-week course of antibiotics with penicillin G was administered. Three months after infection had resolved, the patient had a revision TAA. As demonstrated, the limited TAA infection literature warrants that a treating orthopedic surgeon applies the basic treatment principles derived from infections of knee and hip arthroplasties. ¹

The ultimate decision regarding operative management of patients with infected TAA in general, and reimplantation of those who have undergone a prior resection in particular, lies with the orthopedic surgeon with appropriate consultation of other disciplines such as infectious disease specialists, plastic surgeons, and so on. A 2-stage exchange strategy is commonly indicated in patients who have a chronic infection and are not candidates for a 1-stage exchange arthroplasty. Protocols for management of a patient with infected TAA are extrapolated from the available literature for infected hip and knee arthroplasties. Patients undergoing resection arthroplasty typically receive 4 to 6 weeks of intravenous or highly bioavailable oral antimicrobial therapy between stages.^17,19

The timing to reimplant usually relies on signs of clinical resolution of infection, such as healing of the wound, absence of erythema, and so on as well as a decline in serologic markers of inflammation, namely, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ¹² To determine infection resolution and predict the presence of infection in patients awaiting reimplantation, numerous serologic markers have been evaluated in the past, including interleukin 6 (IL-6) and others. ⁴ The most widely used serologic tests for the diagnosis of periprosthetic joint infection (PJI) are the assessment of ESR and CRP level. A recent publication also suggested the use of serum d-dimer combined with ESR and CRP in order to increase sensitivity and specificity. ¹⁸

In data published about hip and knee surgery, time from resection arthroplasty to reimplantation varies significantly from 2 weeks to several months. In earlier cohort studies, early reimplantation within 3 weeks after resection resulted in a higher failure rate.^10,15 Some groups have reported satisfactory outcomes when reimplantation occurs 2 to 6 weeks after resection while systemic antimicrobials are still being administered in situations when the infection is not due to methicillin-resistant Staphylococcus aureus, enterococci, or any multidrug-resistant gram-negative organisms. ²² Delayed reimplantation after 4 to 6 weeks of intravenous antimicrobial therapy and an antibiotic-free period of 2 to 8 weeks has been highly successful and chosen as the “standard” currently.^2,7,17,20 Recently, synovial fluid biomarkers have been shown to be useful in reaching or refuting the diagnosis of PJI. The combined measurement of synovial fluid alpha-defensin and CRP for the diagnosis of PJI demonstrated a sensitivity of 97% and a specificity of 100%.^3,18 Not only is obtaining synovial fluid invasive and painful to patients, but also there are not infrequent occasions when either an inadequate amount of fluid is available to perform all tests or, worse, no fluid is retrieved from the joint. ¹⁸

Obtaining a prerevision ESR and CRP is recommended to assess the success of treatment prior to reimplantation. ¹¹ However, as some groups have reported, an elevated CRP level and ESR may not be accurate in predicting persistent infection postresection; therefore, the need for subsequent debridement should be interpreted in the context of the entire clinical picture when deciding on the appropriate timing for reimplantation.^5,8,13

In the absence of concrete data, and borrowing from the hip and knee infection literature, we recommend that reimplantation in patients with infected TAA be performed when appropriate antibiotic treatment is completed, clinical signs for resolution of infection are present (healed wound, absent erythema and so on), and the level of inflammatory markers of acute inflammation (ESR, CRP, and possibly d-dimer) has declined substantially (>40%) from its baseline. Further research regarding this issue is desperately is needed.

Supplemental Material