Abstract
Background:
The risk of periprosthetic joint infection (PJI) is higher in persons who inject drugs (PWID) after total joint arthroplasty (TJA), though reported rates vary widely. This study was designed to assess outcomes of TJA in PWID and to describe factors associated with improved PJI outcomes among PWID.
Methods:
A retrospective matched cohort study was performed using a 1:4 match among those with and those without a history of injection drug use (IDU) undergoing TJA. Demographic, surgical, and outcome variables were compared in multivariate logistic regressions to determine PJI predictors. Kaplan-Meier analyses were constructed to characterize the difference in survival of patients who did not have PJI or undergo joint explantation between PWID and the matching cohort.
Results:
PWID had a 9-fold increased risk of PJI compared to the matched cohort (odds ratio 9.605, 95% CI 2.781–33.175, P < .001). Ten of 17 PWID whose last use was within 6 months (active use) of primary TJA had a PJI, while 7 of 41 PWID who did not have active use developed a PJI. Of PWID with PJI, treatment failure was seen in 15 of 17, while in patients who did not have an IDU history, 5 of 8 with PJI had treatment failure.
Conclusion:
IDU is a significant risk factor for PJI following TJA. Future work investigating the effect of a multidisciplinary support team to assist in cessation of IDU and to provide social support may improve outcomes and reduce morbidity in this vulnerable population.
Keywords: periprosthetic joint infection, injection drug use, persons who inject drugs, total knee arthroplasty, total hip arthroplasty
Substance use disorder (SUD) is becoming increasingly common and presents unique challenges in total joint arthroplasty (TJA). Compared to the general arthroplasty population, patients who have a history of injection drug use (IDU) are younger, but often have additional comorbidities including psychiatric disorders, HIV infection, viral hepatitis, congestive heart failure (CHF), pulmonary disease, and active tobacco use [1–3]. Patients who have a history of SUD who undergo TJA also have higher rates of nonhome discharge, patient-directed discharge, 90-day readmission, and inpatient mortality [1,4].
Periprosthetic joint infection (PJI) is one of the most challenging complications in arthroplasty, as it requires revision surgery and may lead to limb loss. In the general population, rates of PJI are estimated to be between 1% and 2% [5]. Persons who inject drugs (PWID) [6] are prone to infectious complications, including a 16-fold higher risk of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection [7], as well as other musculoskeletal infections [8]. Given the concern for increased PJI risk, the 2018 International Consensus Meeting on Musculoskeletal Infection recommended that patients who have active IDU not be offered elective arthroplasty [9]. Although it is acknowledged that PJI risk is higher in PWID, reported rates are from small case series and demonstrate high variance, ranging from 31% to 87% [10–12]. The largest published collection of arthroplasty case outcomes in PWID included 27 joints, but did not include a comparison to a matched cohort [13]. A larger study of arthroplasty patients directly compared PJI rates between those who did and did not have substance abuse (n = 103 and n = 383, respectively), but those who had SUD included persons who did and did not have IDU, such as alcohol use [3].
In this study, we aimed to better characterize rates and outcomes of PJI in PWID and to compare these to patients who did not have IDU undergoing arthroplasty. The secondary aims of this study were to further describe standard outcomes (eg, discharge dispositions, revision rates, and surgical complications) of primary TJA in PWID. Such knowledge may facilitate improved preoperative and postoperative risk management strategies to reduce PJI risk and improve outcomes after TJA in PWID.
Methods
We conducted a retrospective matched cohort study within a large tertiary hospital system in the northeast United States. We first identified all patients who had a history of IDU (ie, subcutaneous, intramuscular, intravenous) who underwent primary TJA from January 1, 2000 to March 31, 2020. The data were obtained from our institutional TJA registry (47,523 primary TJA procedures) and included patients who had the following terms present in an operative or clinic note: “injection drug abuse/use,” “intravenous drug abuse/use,” “IDA,” “IVDA,” “IVDU,” “heroin,” “cocaine,” “opiate abuse,” “methamphetamine,” and/or 10 additional recreational and prescription drugs. A total of 99 patients were identified. After additional chart review, patients were included if they had a history of IDU prior to primary hip or knee TJA, were over 18 years of age at index TJA, and had a minimum of 2 years of clinical follow-up. Type(s) of drugs injected, timing of last documented IDU prior to the TJA, and documented relapse after TJA were also recorded. A total of 58 TJAs in 41 PWID met inclusion criteria.
Using the same institutional database, PWID was matched 1:4 (58:232) for the following variables: age (± 5 years), body mass index (±5), gender, joint (hip or knee), and TJA indication. Chart review was performed to confirm that none of the matched patients had any history of IDU. A total of 58 TJAs among PWID and 232 TJAs among matched patients were included in the analysis; the mean follow-up duration among both PWID and the matched cohort was 7 years (range for both 2–20 years). Among PWID, the mean age was 53 years (range 18–75) and the average body mass index was 32 kg/m2 (range 18–47). There were more men than women in the IDU cohort (62.1% versus 37.9%) and more total hip arthroplasties than total knee arthroplasties (67.2% versus 32.8%). Osteoarthritis was the most common TJA indication (69.0%).
Collected unmatched variables included American Society of Anesthesiologists (ASA) score, CHF, diabetes mellitus, atherosclerotic cardiovascular disease, chronic kidney disease, pulmonary disease, mood disorder, viral hepatitis, HIV, active malignancy, previous septic arthritis in joint other than the primary TJA, presence of multiple prosthetic joints in situ, homelessness within 2 years of primary TJA, regular alcohol use (defined as >1 drink per week to the upper limits of normal) [14], smoking history, and the results of MRSA and methicillin-sensitive S aureus nasal screening prior to primary TJA. Antibiotic allergies, perioperative antibiotic prescriptions, and usage of antibiotic-laden cement in TJA fixation were also collected for each patient.
Outcome variables were also collected, including discharge dispositions following TJA, 90-day emergency department presentations, 90-day PJIs, 90-day surgical site infections [15], 6-month venous thromboemboli, 1-year joint-related readmissions, 1-year all-cause revisions, and any PJI diagnoses during follow-up. Diagnosis of PJI prior to 2011 was made according to the clinical judgement by the treating orthopaedic and infectious disease physicians. After 2011, the diagnosis of PJI utilized Musculoskeletal Infection Society criteria [16–18]. PJI was classified as “early,” “late,” or “delayed” depending on the time of its occurrence after the primary TJA (<3, 3–12, >12 months, respectively) [16,19]. Of patients who had PJI, we identified the causative organism when known, whether same-organism bacteremia occurred 30 days prior to diagnosis, whether a surgical procedure was performed (including debridement, antibiotics, and implant retention; explantation; or single stage revision), discharge dispositions after PJI hospitalization, whether later reimplant was performed, use of chronic antibiotic suppression (>3 months duration), and documented nonadherence to antimicrobial therapy. The causative organism of the PJI was classified as multidrug-resistant if the organism was MRSA or was resistant to >3 antibiotic classes [20]. PJI outcome was classified as described by Fillingham et al [21]. We defined treatment success as a Tier 1 outcome and treatment failure as a Tier 2 through Tier 4 outcome.
Simple descriptive statistics such as means, standard deviations, and percentages were calculated for continuous and categorical variables within groups. Comparisons between groups were performed using Student’s t-tests for continuous variables; chi-squared and Fisher’s exact tests were utilized as appropriate for categorical variables. Multivariate logistic regressions were performed to determine predictors of PJI diagnosis using variables showing some association in univariate analyses, defined as P < .20. Odds ratios (ORs) and 95% CIs were calculated. The final regression model is shown in Table 3. Two Kaplan-Meier survival curves were constructed to understand the differences in infection-free joint survival (no PJI diagnosis) and joint survivorship (no explantation) between PWID and the matched cohort. Log-rank tests were performed to determine statistical differences in survivorship between the groups. P values <.05 were considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26 (IBM Corp).
Table 3.
Multivariable Logistic Regression for Predictors of PJI in Our Patient Cohort.
| Variable | Odds Ratio | 95% CI | P Value |
|---|---|---|---|
| Indication for TJA: osteoarthritis | 0.255 | 0.075–0.866 | .028 |
| Reference: postinfectious arthritis and osteonecrosis | |||
| Indication for TJA: postinfectious arthritis | 3.081 | 0.368–25.783 | .299 |
| Reference: osteoarthritis and osteonecrosis | |||
| ASA physical: 3 | 4.934 | 1.251–19.469 | .023 |
| Reference: ASA physical: 2 | |||
| BMI (kg/m2) | 1.046 | 0.961–1.137 | .297 |
| ASCVD | 0.715 | 0.190–2.690 | .620 |
| CHF | 1.071 | 0.180–6.362 | .940 |
| Pulmonary disease | 0.820 | 0.284–2.362 | .713 |
| Any history of IDU in the past | 9.605 | 2.781–33.175 | <.001 |
| Homelessness within 2 y of index TJA | 1.653 | 0.325–8.392 | .545 |
| Previous septic joint in different joint | 0.258 | 0.025–2.627 | .253 |
| Discharge disposition: home | 1.314 | 0.214–8.086 | .768 |
| Reference: rehab, SNF, SDD | |||
| Discharge disposition: rehab | 5.418 | 0.643–45.660 | .120 |
| Reference: home, SNF, SDD |
Viral hepatitis, mood disorder, and HIV infection could not be included in the regression since these variables display collinearity with the “IDU history” variable. Bolded values represent statistical significance.
ASA, American Society of Anesthesiologists physical score; ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CHF, congestive heart failure; IDU, injection drug use; PJI, periprosthetic joint infection; SDD, self-directed discharge; SNF, skilled nursing facility; TJA, total joint arthroplasty.
Results
PWID were found to have high rates of many medical and social comorbidities (Table 1). A total of 25 of 290 participants developed a PJI during the study follow-up (Table 2). Notably, PWID suffered PJI at an overall rate of 29.3% at any point during the follow-up period. Among PWID, PJI cases were classified as early (29.4%), delayed (35.3%), and late (35.3%). Patients who did not have a history of IDU tended to have early PJI (62.5%) rather than delayed PJI (37.5%), with no cases of late PJI in this matched group (Table 2).
Table 1.
Unmatched Variables and Demographics.
| Variable | TJA Among Patients Who Did Not Have a History of IDU (n = 58) | TJA Among Patients Who Did Not Have a History of IDU (n = 232) |
|---|---|---|
| Year of surgery (range) | 2012 (2000–2020) | 2012 (2000–2020) |
| ASA physical class | ||
| 2 | 12 (20.7) | 123 (53.0) |
| 3 | 42 (72.4) | 81 (34.9) |
| 4 | 1 (1.7) | 1 (0.4) |
| CHF | 13 (22.4) | 14 (6.0) |
| Diabetes | 9 (15.5) | 42 (18.1) |
| ASCVD | 28 (48.3) | 57 (24.7) |
| Previous septic joint in joint other than primary TJA | 6 (10.3) | 3 (1.3) |
| Presence of multiple prosthetic joints in situ | 17 (29.3) | 60 (25.9) |
| Results of MRSA screen prior to TJAa (n = 189) | ||
| MRSA | 5 (11.9) | 6 (4.1) |
| MSSA | 4 (9.5) | 26 (17.7) |
| Negative | 33 (78.6) | 115 (78.2) |
| Antibiotic allergies | ||
| Penicillins | 12 (20.7) | 36 (15.5) |
| Cephalosporins | 3 (5.2) | 8 (3.4) |
| Multiple drug classes | 7 (12.1) | 17 (7.3) |
| Perioperative antibiotic given at index TJA | ||
| Cefazolin | 51 (87.9) | 211 (91.0) |
| Vancomycin | 2 (3.4) | 14 (6.0) |
| Other | 5 (8.6) | 7 (3.0) |
| Antibiotic-laden bone cement used in TJA fixation | 5 (8.6) | 7 (3.0) |
| Chronic kidney disease | 5 (8.6) | 23 (9.9) |
| Pulmonary disease | 30 (51.7) | 56 (24.1) |
| Mood disorder | 42 (72.4) | 72 (31.0) |
| Viral hepatitis | 39 (67.2) | 5 (2.2) |
| HIV | 3 (5.2) | 1 (0.4) |
| Active malignancy | 14 (24.1) | 54 (23.3) |
| Regular alcohol user (at least one drink per week) | 27 (46.6) | 72 (31.1) |
| Any smoking history | 52 (89.8) | 99 (42.7) |
| History of homelessness within 2 y of primary TJA | 14 (24.1) | 0 (0) |
ASA, American Society of Anesthesiologists physical score; ASCVD, atherosclerotic cardiovascular disease; CHF, congestive heart failure; IDU, injection drug use; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; TJA, total joint arthroplasty.
MRSA/MSSA screening was fully initiated at our institution in 2010.
Table 2.
Outcome Variables.
| Variable | TJA Among Patients Who Did Not Have a History of IDU (n = 58) | TJA Among Patients Who Did Not Have a History of IDU (n = 232) |
|---|---|---|
| Discharge disposition from primary TJA | ||
| Home with services | 40 (69.0) | 209 (90.1) |
| Rehabilitation | 10 (17.2) | 11 (4.7) |
| Patient-directed discharge | 1 (1.7) | 0 (0) |
| SNF | 7 (12.1) | 3 (1.3) |
| Postoperative variables | ||
| 90-d ED presentation | 19 (32.8) | 23 (9.9) |
| 90-d PJIa | 6 (10.3) | 6 (2.6) |
| 90-d SSIb | 0 (0) | 2 (0.9) |
| 6-mo VTE | 3 (5.2) | 3 (1.3) |
| 1-y joint-related readmission | 12 (20.7) | 20 (8.6) |
| 1-y all-cause readmission | 21 (36.2) | 36 (15.5) |
| 1-y revision | 14 (24.1) | 17 (7.3) |
| Any PJI within follow-up period | 17 (29.3) | 8 (3.4) |
| Early PJI (<3 mo from index TJA) | 5 (29.4) | 5 (62.5) |
| Delayed PJI (3–24 mo from index TJA) | 6 (35.3) | 3 (37.5) |
| Late PJI (>24 mo from index TJA) | 6 (35.3) | 0 (0) |
| Bacteremia 30 d prior to PJI diagnosis (positive blood cultures of PJI organism) | 7 (41.2) | 0 (0) |
| PJI organism | ||
| MSSA | 7 (41.2) | 2 (25) |
| CoNS | 0 (0) | 2 (25) |
| MRSA | 3 (17.6) | 0 (0) |
| Streptococcus | 0 (0) | 2 (25) |
| Fungal | 3 (17.6) | 0 (0) |
| Gram-negative organism | 3 (17.6) | 0 (0) |
| Enteric | 3 (17.6) | 0 (0) |
| Nonenteric | 0 (0) | 0 (0) |
| Polymicrobial | 0 (0) | 2 (25) |
| No growth | 0 (0) | 0 (0) |
| MDR organism | 4 (23.5) | 1 (12.5) |
CoNS, coagulase-negative staphylococci; ED, emergency department; IDU, injection drug use; MDR, multidrug resistant; MRSA, methicillin-resistant Staphylococcus aureus; MSIS, Musculoskeletal Infection Society; MSSA, methicillin-susceptible Staphylococcus aureus; PJI, periprosthetic joint infection; SNF, skilled nursing facility; SSI, surgical site infection; TJA, total joint arthroplasty; VTE, venous thromboembolism.
PJI defined according to the available MSIS criteria at the time after 2012, and prior to 2012, PJI was defined according to the available clinical and infectious criteria to the orthopaedic and infectious disease services.
Defined as superficial surgical site infection according to the Centers for Disease Control and Prevention criteria.
In total, 32.8% of PWID presented to the emergency department within 90 days of primary TJA, 20.7% had a joint-related readmission at 1 year, 36.2% had a readmission for any cause, and 24.1% underwent revision for any cause within 1 year (Table 2). Following the index TJA, 17.2% of PWID were discharged to a rehabilitation facility and 12.1% to a skilled nursing facility. Of those who had a PJI, 41.2% of PWID had bacteremia within 30 days prior to the PJI, while no patients in the matched group were found to have bacteremia prior to the PJI. MRSA (17.6%), fungal (17.6%), and Gram-negative organisms (17.7%) were only found in patients who had IDU; 23.5% of the infections in the PWID cohort were caused by multidrug-resistant organisms (Table 2). Of PWID, 50% had an addiction medicine consultation at the time of the index TJA, and 48.3% of patients were on medication-assisted treatment (MAT) including methadone or buprenorphine/naloxone at the time of primary TJA. In PWID whose last IDU was within 6 months of TJA (active use), 10 of 17 developed PJI, while 7 of 41 PWID who did not have active use had PJI. In total, 17.64% of PWID diagnosed with PJI were documented to have treatment nonadherence. In addition, 35.3% of PWID who experienced PJI and none of those in the matched group had a Tier 3E outcome (ie, amputation, resection arthroplasty, or arthrodesis).
In multivariate analyses, osteoarthritis as the indication for the index TJA was associated with a decreased risk of PJI (OR 0.255, 95% CI 0.075–0.866, P = .028) although this was a matched variable between cohorts and as such potentially biased (Table 3). An ASA physical score of 3 and any history of IDU had significantly increased odds of PJI (OR 4.934, 95% CI 1.251–19.469, P = .023 and OR 9.605, 95% CI 2.781–33.175, P < .001, respectively). Several variables (viral hepatitis, mood disorder, HIV infection, and recent IDU within 6 months of TJA) displayed collinearity with any prior IDU history and therefore could not be included in the regression.
Figures 1 and 2 display the Kaplan-Meier curves and log-rank analyses. PWID undergoing TJA had significantly lower infection-free joint survival (log-rank P < .001) and significantly lower joint retention (log-rank P < .001).
Fig. 1.
Survival curve comparing time to periprosthetic joint infection in patients with history of injection drug use (green) to matched controls (blue). Long-rank test demonstrated P < .001 between the 2 groups.
Fig. 2.
Survival curve comparing time to periprosthetic joint infection requiring explant in patients with history of injection drug use (green) to matched controls (blue). Long-rank test demonstrated P < .001 between the 2 groups.
Discussion
In this retrospective matched cohort study, baseline characteristics and outcomes of 58 TJAs in 41 PWID were analyzed and compared to 232 matched TJA patients who did not have IDU. To the best of our knowledge, this study is the largest to date assessing PJI risk and outcomes of TJA in PWID [10–13]. Overall, PWID undergoing TJA were medically complex, had complicated discharges, and suffered a high degree of complications, including PJI.
Poor outcomes among PWID may reflect greater medical complexity. In this study, PWID undergoing TJA had high ASA physical scores, often had HIV and viral hepatitis [22], and had high rates of mood disorders, pulmonary disease, atherosclerotic cardiovascular disease, and CHF. These findings are similar to other studies of arthroplasty in patients with SUD [3]. PWID also frequently had a history of prior septic arthritis, consistent with studies demonstrating IDU as the most important risk factor for septic arthritis during the opioid epidemic [8]. In this study, as in other studies [23], PWID also had high rates of alcohol and tobacco use. Although 11.9% of PWID had nasal colonization with MRSA, a regional decline in MRSA prevalence during the study period may explain lower rates of MRSA carriage than expected [24].
In this study, a prior history of IDU was more strongly associated with PJI (OR 9.61, CI 2.781–33.175) than any other factor. This is consistent with models built from large datasets. In the development of a calculator for predicting preoperative risk for PJI, drug abuse (though not specific to IDU) was the most predictive comorbidity after an analysis of over 27,000 patients following TJA [25].
The PJI rate among PWID undergoing TJA was similar to or lower than reported in other studies. One study found a 12% rate of PJI among 17 PWID who were on MAT at the time of arthroplasty [26]. Another found a low rate (6%) of PJI among 103 persons with SUD with documented abstinence prior to TJA [3]. Taken together, these studies suggest that efforts to improve abstinence among PWID may reduce the risk of PJI. Although our study identified a trend towards relapsed IDU being associated with PJI, this was not statistically significant. Documentation of relapse, however, was not consistently reported and may have biased these results.
Persons who have active IDU are at risk for hematogenous dissemination of organisms introduced from contaminated equipment and/or from host skin and oral flora, which may lead to PJI [11]. In this study, more than a third of PJI cases in PWID occurred more than 24 months after arthroplasty, suggesting hematogenous dissemination as opposed to direct inoculation, whereas no cases of PJI occurred during this period in the matched cohort. In addition, prior bacteremia with the same organism only occurred in the PWID cohort. Although not definitive, these findings further suggest that hematogenous infection is of major importance in PWID PJI.
As the opioid epidemic unfolded, addiction medicine consultations were introduced at different times during the study period in participating hospitals. Among PWID undergoing TJA, 50% received addiction medicine consults, but due to low sample size, we were unable to extrapolate the effect that these consults had on PJI outcomes. Studies have demonstrated improved PWID engagement in other IDU-associated infections such as endocarditis with the creation of formal multidisciplinary programs including surgeons, infectious disease and addiction medicine specialists, social workers, recovery coaches, and pharmacists [27,28]. Given that this patient population has more social vulnerabilities, a similar multidisciplinary approach for TJA in PWID may improve TJA and PJI outcomes.
This study has several important limitations. Diagnosis of IDU relies upon thorough history-taking, patient disclosure, and/or drug screening programs, but these are not universally applied. It is possible that some individuals in the non-PWID cohort may have had unrecognized IDU, diluting the association between PWID and PJI. In addition, despite demographic matching, PWID undergoing TJA differed from the matched cohort in additional comorbid factors. Although many of these factors were adjusted for in our regression analyses, we could not fully exclude that other comorbidities may be associated with PJI rates and outcomes in our cohort. This study followed patients for many years, yet PWID are more prone to housing insecurity, relapse, and other complications of IDU that impact clinical follow-up. TJA complications may not have been identified at the facilities where TJA was performed, leading to incomplete outcomes data. Also, this study was not powered to detect differences in PJI outcomes (treatment tiers) between cohorts, or to understand whether more recent interventions not widely available during the entire study period (such as Addiction Medicine consultation and MAT) impact outcomes. Further studies should also be performed to understand if different intraoperative techniques, such as use of antibiotic-laden bone cement in PWID, may prevent PJI cases. Additional study focused on the role of these interventions and multidisciplinary programs on TJA outcomes for PWID are needed.
Conclusion
IDU is an important risk factor for PJI following TJA. We believe this to be the largest study of TJA in PWID to date which is further strengthened by the use of a matched cohort. PWID had a 9-fold higher risk of PJI after primary TJA compared to a matched cohort, and when “active” drug users underwent primary TJA, 10 of 17 experienced PJI. PWID also had serious PJI outcomes, with >35% of cases ultimately ending with amputation, resection arthroplasty, or arthrodesis. Future studies can evaluate implementation of interventions such as Addiction Medicine consultation, MAT, and multidisciplinary care teams which may facilitate durable abstinence and provide needed social support to reduce morbidity and improve TJA outcomes in this vulnerable population.
Acknowledgments
A.M.T. received support from NIH T32 AI007061.
Footnotes
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2022.07.018.
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