Abstract
Background
We sought to evaluate reoperation-free survival following I&D with modular component exchange of revision total joint arthroplasty (TJA).
Methods
Of revision TJAs from 2004 to 2012 (n = 4,166), 30 were I&D with modular component exchange after index revision for aseptic indications. Patients with (n = 12) and without (n = 18) reoperation for infection recurrence were analyzed.
Results
Reoperation-free survival (60% at mean 4.8 year follow-up) improved with increased duration of antibiotic therapy (p = 0.0185), with maximum benefit at 2 years.
Conclusions
At least 2 years of antibiotic therapy should be administered after I&D with modular component exchange for acutely infected revision TJA.
Level of evidence
Level III, retrospective comparative study.
Keywords: Hip, Knee, Total joint arthroplasty, Infection, Irrigation and debridement
1. Introduction
The incidence of revision TJA is increasing at a rate even faster than that of primary TJA.1 With an infection rate higher than that of primary TJA, revision TJA is poised to add significantly to the PJI burden.2, 3, 4 Acute PJI may be treated with irrigation and debridement (I&D) with modular component exchange. However, the success rate of I&D with modular component exchange has been reported to be as low as 40%–50%.5, 6, 7, 8 This is of particular concern when considering PJI following revision TJA. Failed I&D with modular component exchange may necessitate removal of long cemented stems in the knee or distally well-fixed stems in the hip, resulting in significant bone loss and limited options for reconstruction.
Efforts to increase the success of I&D with modular component exchange following revision TJA are thus essential. Type of infecting organism and timing of surgery have been shown to impact survival after I&D with modular component exchange of primary TJA.5, 6, 7, 8 We have recently reported that reoperation-free survival improves with longer antibiotic duration after I&D with modular component exchange of primary total hip or knee arthroplasty.9,10 To our knowledge, survivorship of I&D with modular component exchange following revision TJA, however, has not yet been studied in isolation.
The aims of our study were to determine if: 1) postoperative antibiotic duration; 2) infecting organism; 3) timing of infection onset; or 4) patient characteristics or surgical factors affect reoperation-free survival following I&D with modular component exchange of revision TJA.
2. Methods
2.1. Study design
Our approach to studying this retrospective cohort was similar to our earlier work on related topics.9,10 Briefly, we reviewed 4,166 patients who underwent revision TJA (any reoperation following TJA) at our institution from 2004 to 2012. Cases were included upon first I&D with modular component exchange performed for acute PJI (less than 4 weeks of symptoms) occurring after TJA revision surgery during which at least one component was revised. Musculoskeletal Infection Society (MSIS) criteria were used to define PJI.11 Patients who underwent treatment for PJI of the same joint prior to I&D with modular component exchange, two-stage revision TJA, more than 1 revision surgery prior to I&D with modular component exchange, or I&D with modular component exchange performed less than 2 years prior to the end of the follow-up period were excluded from the analysis. Thirty patients remained after applying the described inclusion and exclusion criteria and were comprised of those who required reoperation for infection recurrence (n = 12) and those who did not (n = 18) (Fig. 1). All cases were performed at a single hospital by thirteen fellowship-trained, adult reconstructive surgeons. The Institutional Review Board at our institution approved this study.
Fig. 1.
Method to identify all patients who underwent I&D with modular component exchange after revision TJA performed for aseptic indications from 2004 to 2012, and the cohorts analyzed.
Intravenous antibiotics were administered to all patients after I&D with modular component exchange for six weeks. The infectious disease consult service at our institution established the type and duration of oral antibiotic therapy thereafter, based on infecting organism, duration of infection, host factors, and intraoperative findings.
Reoperation for recurrence of infection, as defined by MSIS criteria, was the primary outcome measure for this study. Our study cohort had a mean duration of 3.0 years follow-up (range 0.1–9.1 years). Those who underwent reoperation due to recurrence of infection had mean 0.4 years follow-up (range 0.1–0.8 years). Patients who did not require additional surgery had mean 4.8 years follow-up (range 2.0–9.1 years). All patients included in the retrospective analysis had at least 2 years of available follow-up; when recorded at less than two years, it was secondary to a reoperation for infection that took place within two years of I&D with modular component exchange.
A systematic chart review aimed to record a number of variables as previously reported,9,10 including but not limited to time to onset of infection, causative organism, parameters of antibiotic therapy postoperatively, and any reoperation.
2.2. Statistical analysis
General demographic factors and comorbidities were compared between patients who underwent reoperation for infection and those who did not require reoperation using Chi-square test, Fisher's exact test, and one-way ANOVA. The primary variable of interest was any association between the length of antibiotic administration and survival without reoperation. This was evaluated by building a multivariate survival analysis applying Cox regression. Given the sample size, stepwise selection with two forcing variables (antibiotic duration and type of surgery) was employed to ensure the most relevant covariates remained in the final Cox model (covariates with p < 0.05 entered and stayed in the final model). Multivariable regression was used to predict the probability of reoperation-free survival for each additional week of antibiotic administration. The effect size of infection recurrence between two groups of infecting organisms was measured as previously described,9,10 applying a standardized difference calculation. Acute postoperative infection was defined as occurring within four weeks of index revision TJA while acute hematogenous infection was defined as occurring more than four weeks after index revision TJA. The two groups were compared using mulitvariate Cox regression, with the same set of covariates generated from stepwise selection. Using a hazard ratio of 0.34, the power necessary to detect an effect of length of antibiotic administration on survival without reoperation was 0.80. SAS software version 9.4 was used to conduct statistical analysis and manipulate the data (SAS Institute Inc.; Cary, NC).
3. Results
General demographics and characteristics of each patient cohort, along with a univariate analysis, are presented in Table 1. Among patients who underwent I&D with modular component exchange, 60.0% remained reoperation-free at mean follow-up of 4.8 years. Table 2 presents the results of the regression model. There was no difference in risk of reoperation between acutely infected revision total hip and revision total knee arthroplasties following I&D with modular component exchange.
Table 1.
Univariate analysis across covariates among patients who underwent I&D with modular component exchange of acutely infected revision TJA.
| All Patients (n = 30) | Reoperation for Infection (n = 12) | Reoperation Free (n = 18) | p-value | |
|---|---|---|---|---|
| Age (Mean, SD) | 67 (13.4) | 65 (15.8) | 68 (11.9) | 0.6135 |
| BMI (Mean, SD) | 30.3 (6.8) | 30.4 (6.9) | 30.3 (7.0) | 0.9671 |
| Weeks of antibiotic use (Mean, SD) | 70.5 (108.1) | 16.6 (7.1) | 106.4 (128.3) | 0.0086 |
| Type of revision surgery | 0.3668 | |||
| TKA | 17 (56.7%) | 8 (66.7%) | 9 (50%) | |
| THA | 13 (43.3%) | 4 (33.3%) | 9 (50%) | |
| Infecting organism | 0.0014 | |||
| Non S. aureus | 22 (73.3%) | 5 (41.7%) | 17 (94.4%) | |
| S. aureus | 8 (26.7%) | 7 (58.3%) | 1 (5.6%) | |
| Atrial fibrillation | 0.8038 | |||
| Yes | 3 (10%) | 1 (8.3%) | 2 (11.1%) | |
| No | 27 (90%) | 11 (91.7%) | 16 (88.9%) | |
| Cells per high-powered field | 0.9026 | |||
| ≤15 | 14 (46.7%) | 5 (41.7%) | 9 (50%) | |
| >15 | 7 (23.3%) | 3 (25%) | 4 (22.2%) | |
| Unknown | 9 (30%) | 4 (33.3%) | 5 (27.8%) | |
| Tissue pathology | 0.6794 | |||
| Acute inflammation | 1 (3.3%) | 0 (0%) | 1 (5.6%) | |
| Chronic inflammation | 13 (43.3%) | 5 (41.6%) | 8 (44.5%) | |
| Not recorded | 16 (53.3%) | 7 (58.3%) | 9 (50%) | |
| Smoker | 0.073 | |||
| Yes | 14 (46.7%) | 8 (66.7%) | 6 (33.3%) | |
| No | 16 (53.3%) | 4 (33.3%) | 12 (66.7%) | |
| Alcohol use | 0.3668 | |||
| Yes | 17 (56.7%) | 8 (66.7%) | 9 (50%) | |
| No | 13 (43.3%) | 4 (33.3%) | 9 (50%) | |
| Hypertension | 0.4809 | |||
| Yes | 23 (76.7%) | 10 (83.3%) | 13 (72.2%) | |
| No | 7 (23.3%) | 2 (16.7%) | 5 (27.8%) | |
| Hypercholesterolemia | 0.4292 | |||
| Yes | 10 (33.3%) | 3 (25%) | 7 (38.9%) | |
| No | 20 (66.7%) | 9 (75%) | 11 (61.1%) | |
| Diabetes | 0.1921 | |||
| Yes | 6 (20%) | 1 (8.3%) | 5 (27.8%) | |
| No | 24 (80%) | 11 (91.7%) | 13 (72.2%) | |
| Coronary artery disease | 0.7651 | |||
| Yes | 2 (6.7%) | 1 (8.3%) | 1 (5.6%) | |
| No | 28 (93.3%) | 11 (91.7%) | 17 (94.4%) | |
| History of malignancy | 0.0455 | |||
| Yes | 5 (16.7%) | 0 (0%) | 5 (27.8%) | |
| No | 25 (83.3%) | 12 (100%) | 13 (72.2%) | |
| Renal insufficiency | 0.073 | |||
| Yes | 2 (6.7%) | 2 (16.7%) | 0 (0%) | |
| No | 28 (93.3%) | 10 (83.3%) | 18 (100%) | |
| COPD | 0.2129 | |||
| Yes | 1 (3.3%) | 1 (8.3%) | 0 (0%) | |
| No | 29 (96.7%) | 11 (91.7%) | 18 (100%) | |
Table 2.
Multivariate analysis of risk of reoperation for infection after I&D with modular component exchange of acutely infected revision TJA.
| Predictors | Hazard Ratio | 95% CI | p-value |
|---|---|---|---|
| Weeks of antibiotic use | 0.912 | 0.845–0.985 | 0.0185 |
| S. aureus | 17.5 | 3.027–101.186 | 0.0014 |
| Type of revision surgery (THA vs. TKA) | 3.12 | 0.7–13.908 | 0.1357 |
Increased duration of postoperative antibiotic therapy (HR 0.912, 95% CI 0.845 to 0.985, p = 0.0185) following I&D with modular component exchange decreased the risk of reoperation for infection. In a plot of reoperation-free survival versus antibiotic duration, the curve plateaued at 100 weeks of antibiotic administration (Fig. 2).
Fig. 2.
Predicted probability of reoperation-free survival with each additional week of antibiotic administration after I&D and modular component exchange of acutely infected revision TJA.
The risk of reoperation for infection recurrence following I&D with modular component exchange was variable depending on infecting organism (Table 3). Using standardized difference scores, we found that S. aureus had the highest incidence of infection recurrence. There was no difference in incidence of infection recurrence between Gram negative organisms and other organisms. Culture negative infections had a lower incidence of infection recurrence than other organisms, non S. aureus staphylococcal infection recurrence was lower yet, while non staphylococcal Gram positive organisms had the lowest incidence of infection recurrence.
Table 3.
Standardized difference scores for reoperation for infection between one infecting organism versus all others. Organisms are listed in order of highest to lowest incidence of reoperation for infection.
| Infecting Organism | Standardized Difference Score |
|---|---|
| S. aureus | 1.3730 |
| Gram negative | 0.0000 |
| Culture negative | −0.3430 |
| Non S. aureus staphylococcus | −0.5121 |
| Non staphylococcal Gram positive | −0.7559 |
*Positive values denote higher incidence of reoperation for infection, while negative values denote lower incidence of reoperation for infection.
There was no observed difference in reoperation-free survival between acute postoperative and acute hematogenous infections after revision TJA treated with I&D plus modular component exchange upon multivariate analysis (p = 0.2152).
No patient characteristics or surgical factors affected reoperation-free survival in univariate or multivariate analysis.
4. Discussion
I&D with modular component exchange is an appealing treatment option for acute PJI as it minimizes number of surgeries, avoids the limited weight-bearing/mobility afforded by an antibiotic spacer, and has reasonable rates of success.12,13 In the treatment of PJI following revision TJA, I&D with modular component exchange has the added advantage of minimizing morbidity associated with removal of well-fixed long-stemmed implants. We have previously reported that reoperation-free survival following I&D with modular component exchange of primary TJA improves with longer duration of postoperative antibiotic therapy.9,10 However, the factors affecting reoperation-free survival following I&D with modular component exchange of revision TJA are unknown. We found that postoperative antibiotic duration and infecting organism, but not other patient/surgical factors or timing of infection onset, affect likelihood of success of I&D with modular component exchange after revision TJA. To the best of our knowledge, we are the first to report the outcomes of a patient cohort that has exclusively undergone I&D with modular component exchange following revision TJA.
Although our study may provide guidance in the management of PJI following revision TJA, we understand our work has limitations. First, as a retrospective study, our data and conclusions are impacted by the completeness of available records. Second, characteristics unique to our patient cohort may narrow the generalizability of our findings. Third, while our findings may be influenced by the small numbers in our study cohort, we studied a rare event that comprised less than 1% of all revision TJA patients at a high-volume orthopaedic specialty hospital. Finally, we recognize that our study endpoint of reoperation for infection recurrence does not preclude the persistence of subclinical infection among those patients that did not require reoperation.
60.0% of patients were reoperation-free after I&D with modular component exchange of revision TJA at 4.8 year mean follow-up. This rate of success is comparable to those reported in modern studies of I&D with modular component exchange of primary TJA, which range from 68.7% to 78.6%.12,13 As a result, I&D with modular component exchange is a reasonable treatment strategy for acute PJI after revision TJA performed for aseptic indications.
Reoperation-free survival improved with increased duration of antibiotic therapy following I&D with modular component exchange of revision TJA, with maximum benefit observed after 2 years of antibiotic administration. Thus, chronic oral antibiotic suppression should be considered in all patients who have undergone I&D with modular component exchange for acutely infected revision TJA. Chronic antibiotic suppression, by reducing the likelihood of TJA explant, also has the potential to minimize bone loss and morbidity associated with removal of well-fixed long-stemmed revision implants.
The incidence of reoperation for infection after I&D with modular component exchange of revision TJA is highest when S. aureus is the infecting organism. This finding is in agreement with our prior work and that of our colleagues on I&D with modular component exchange of primary TJA.9,10,14,15 Other infecting organisms in decreasing order of incidence of reoperation for infection after I&D with modular component exchange of revision TJA are: Gram negative, culture negative, non S. aureus staphylococcus, and non staphylococcal Gram positive. Again, these observations concur with previous work that has found culture negative and gram negative infections, despite difficulty with antibiotic selection and systemic virulence, respectively, have favorable outcomes after I&D with modular component exchange of primary TJA.5,9,10,16, 17, 18
Acute postoperative and acute hematogenous infections after revision TJA are equally well-eradicated by I&D with modular component exchange. Many studies of I&D with modular component exchange of primary TJA have arrived at the same conclusion.9,10,15,19,20 Thus, I&D with modular component exchange is an effective strategy for treatment of acute infection regardless of timing of infection onset.
Though we previously found patient characteristics and surgical factors impact reoperation-free survival after I&D with modular component exchange of primary TJA,1,2 our current study did not demonstrate this to be true of revision TJA. The heterogeneity and limited size of the patient cohort herein may have prevented the elucidation of these associations.
Reoperation-free survival after I&D with modular component exchange of revision TJA is 60.0% at mean 4.8 year followup and improves with increased duration of postoperative antibiotic therapy. Two-stage exchange should be considered when a revision TJA is acutely infected with S. aureus. Future work will include a multicenter study of I&D with modular component exchange of revision TJA in order to increase the size and diversity of patient cohorts. This may allow for the identification of additional modifiable factors that improve the outcomes of I&D with modular component exchange.
Declaration of competing interest
On behalf of all authors, the corresponding author declares that there are no conflicts of interest.
Acknowledgements
The authors would like to thank Drs. Susan Davidson and Gerald Miley for their assistance with this project.
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