Peri-Prosthetic Joint Infection in Patients Prescribed Suppressive Antibiotic Therapy Undergoing Primary Total Joint Arthroplasty: A 1:4 Case Control Matched Study

Abstract

Background:

Oral suppressive antibiotic therapy (SAT) has emerged as a potential means to increase rates of infection-free survival in many complex peri-prosthetic joint infection (PJI) cases after total joint arthroplasty (TJA). The purpose of the present study is to evaluate the risk of PJI of a new primary TJA in patients on oral SAT.

Patients and Methods:

A retrospective matched cohort study from five hospitals in a 20-year period within a large hospital network was performed. Inclusion criteria consisted of patients over age 18 undergoing primary TJA, with any order for oral long-term (>6 months duration) SAT, and minimum of one-year clinical follow-up. Patients were matched 1:4 on age, gender, body mass index (BMI), hip or knee surgery, diabetes mellitus, smoking status, and indication for primary TJA. Student t-test, Fisher exact, and χ² tests were utilized for group comparisons. Our study was powered to detect a 10.5% increase in PJI incidence compared with a 1% baseline rate of PJI.

Results:

We identified 45 TJA in 33 patients receiving SAT, which were matched to 180 control cases. There was no difference in the rate of development of PJI at any time point within follow-up between the SAT cohort and control group (2.22% vs. 1.11%; p = 0.561).

Conclusions:

We found a 2.22% rate of PJI in a cohort of patients receiving SAT identified over a 20-year period. As the clinical scenario of primary TJA while on SAT is rare but likely to become more prevalent, future large-scale studies can be performed to better clarify rates and risk of PJI in this population.

Peri-prosthetic joint infection (PJI) is one of the most devastating adverse outcomes of total hip arthroplasty (THA) and total knee arthroplasty (TKA), occurring approximately in 1% of cases of primary TJA in the United States.^1–3 The current gold standard management for PJI remains two-stage exchange, with infection eradication occurring in anywhere from 75% to 100% of patients who undergo these staged procedures, whereas debridement, antibiotics, and implant retention (DAIR) has also been utilized with varying efficacy in patients who satisfy its indications.^4–8 Recently, oral long-term antibiotic suppression therapy (SAT) after surgical management for PJI (i.e., DAIR or two-stage exchange with intravenous antibiotic agents) has emerged as a potential means to increase rates of infection-free survival in patients deemed to be at high risk for infection relapse or in patients unable to undergo the re-implant of the two-stage exchange.^9–14 There is no consensus regarding the duration of SAT or choice of antibiotic agent(s); therefore, the antibiotic susceptibility of the infecting organism and a patient's medical history may dictate the appropriate regimen as decided upon by infectious disease and orthopedic providers.¹⁵

As the number of patients undergoing primary TJA increases, so too will the incidence of PJI, and by proxy, the number of patients receiving SAT.¹⁶ Although it is known that prior PJI increases the risk for PJI in a new primary TJA,¹⁷ there is currently a paucity of data highlighting the PJI risk in primary TJA if a patient is currently on SAT indicated for a different TJA PJI or other chronic infection. Chalmers et al.¹⁸ recently evaluated 28 new primary TKAs in 26 patients who were receiving SAT for a prior PJI and found that six joints developed a PJI at a rate of 6 of 28 (21.43%). They also found that patients receiving SAT had 15-fold higher risk of PJI compared with a matched cohort (hazard ratio [HR], 15.2; 95% confidence interval [CI], 8.4–23.2; p = 0.002).

The purpose of the present study is to evaluate further the risk of PJI of a new primary TJA in patients receiving oral SAT through a retrospective matched cohort study. We hypothesized that patients receiving SAT would have no increased risk of PJI compared with a matched cohort, given the promising results of recent randomized control trials supporting the efficacy of SAT in infection suppression in patients with PJI.

Patients and Methods

This is an Institutional Review Board-approved retrospective matched cohort study from five hospitals within a large tertiary hospital network in the northeast United States. Within our hospital network, we identified all patients who were treated with oral SAT for any indication between January 1, 2000, and December 31, 2021, who subsequently underwent a primary TJA contemporaneously. We queried our institution's Outpatient Antibiotic Therapy database (OPAT), which tracked all patients on long-term antibiotic agents (both oral and intravenous routes) from August 2006 to October 2012 (n = 2,640 patients). To obtain data from the years 2000–2006 and 2012–2021, we requested data from our institution's clinical data registry, the Research Patient Data Registry, for all of the patients who had any of the following terms present in an operative note or clinic note: “suppress,” “suppression,” “chronic suppression,” “chronic antibiotics,” “daily,” as well as over 15 brand and generic names of commonly used antibiotic agents for SAT including “Bactrim,” “doxycycline,” and more (n = 320 patients). All patients were then chart-reviewed to determine if they met our study's inclusion criteria: any patients over age 18, patients with any order for long-term oral (>6 months duration) SAT had to have been placed at a maximum of 30 days prior to the date of the TJA, and patients with a minimum of one year clinical follow up from the TJA. This query identified 45 TJAs performed in 33 patients on oral SAT.

For all patients who met inclusion criteria, a chart review was performed to collect the following variables used for matching: age at time of primary TJA, gender, body mass index (BMI) in kg/m², joint of primary TJA (hip or knee), type 2 diabetes mellitus history, smoking history within 6 months of primary TJA, and indication for primary TJA. Age at time of primary TJA and BMI were matched within five points of the original cohort, whereas all other variables were matched for exactly. The 45 TJA were matched 4:1 to a separate database of 47,523 primary TJA patients also from our institutions. Matched controls were confirmed to not have been receiving SAT. Variables collected for both SAT patients and matched controls included American Society of Anesthesiologists (ASA) physical score, Charlson comorbidity index (CCI), regular alcohol use, autoimmune disease, injection drug use, any prior septic joint (native or prosthetic), antibiotic allergies, use of antibiotic-laden bone cement or pearls during the primary TJA, follow-up duration, dates of TJA, and diagnosis of PJI after primary TJA according to the available criteria at the time of diagnosis. Regular alcohol use was defined according to the National Institute on Alcohol Abuse and Alcoholism standard of any drinking activity (>1 drinks per week) for men or women up to the weekly recommended limit.¹⁹ Diagnosis of PJI prior to the year 2011 was made according to the orthopedic surgeon's and infectious disease team's best judgement as identified through chart review; from 2011 to 2013²⁰ and from 2013 to 2018²¹ the diagnosis of PJI was made according to the available Musculoskeletal Infection Society (MSIS) criteria at the time, and from 2018 to 2020 the diagnosis was made according to the most recent MSIS criteria.²²

For patients receiving oral SAT, we collected the indication for the treatment, the infectious organism being suppressed, the agents used for antibiotic suppression, the pre-operative serum erythrocyte sedimentation rate (ESR; mm/hr) and C-reactive protein (CRP; mg/L) of the primary TJA, and the peri-operative antibiotic regimen for the primary TJA. Patients were stratified by indication for oral SAT for further analyses.

For the patients diagnosed with PJI after the primary TJA in our study, we collected the PJI organism, whether DAIR, explant, explant with re-implant, or single-stage exchange was performed, as well as the final infectious outcome, according to the MSIS classification provided by Fillingham et al.²³

Statistical and power analyses

Quantitative variables were assessed with sample mean and standard deviation, and independent Student t-tests were conducted to test for significance between cohorts. Categorical variables were presented as percentages and analyzed using Fisher exact tests and χ² tests as appropriate. All p values of <0.05 were considered statistically significant.

A post hoc power analysis was performed to determine the percent incidence of PJI that we could detect in our SAT cohort compared with the matched cohort. We assumed that our 4:1 matched cohort (n = 180) would have a PJI incidence similar to our institution's annual PJI incidence of approximately 1%. With a relatively small SAT cohort (n = 45), we found that we were powered to detect a 10.5% increase in PJI incidence compared with a 1% baseline rate of PJI at our institution. In essence, we had the ability to significantly detect a PJI rate greater than 11.5% in our SAT cohort. Statistical analyses were performed using SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, NY).

Results

We identified 45 TJA in 33 patients who were receiving oral SAT contemporaneously to their TJA, termed our SAT cohort. A matched cohort of 180 patients was also identified, for a total cohort of 225 patients. Although our inclusion criteria for the study required a minimum one-year follow-up duration, the average follow-up duration was more than four years in both cohorts, with the control group having a longer follow-up duration than the SAT group at 5.50 ± 4.06 years versus 4.10 ± 3.42 years (p = 0.034. All of the patients receiving SAT were still receiving antibiotic agents at the time of the time of the new primary TJA. In 32 of 33 patients or in 44 of 45 joints, the SAT regimen was continued until last follow-up. The one patient who did not continue the SAT therapy throughout the patient's follow-up duration (2.8 years) did not experience a PJI. This patient was diagnosed with THA PJI and had a MSIS Tier 2 treatment outcome, meaning that the patient remained on SAT and refused further surgical intervention.

In the SAT group, the 45 TJAs were performed by 18 different surgeons. In the control group, 41 surgeons performed the 180 surgeries, which was inclusive of the 18 surgeries performing the procedures in the SAT group. All PJIs reported in our study (n = 3) were encountered in surgeries performed by different surgeons.

A description of the matched variables of age, gender, BMI, joint of primary TJA (hip or knee), diabetes mellitus, smoking status, and indication for TJA is shown in Table 1. The average age of patients in our SAT cohort was 67.56 ± 11.26 years, there were 53.37% males and 46.66% females, and the average BMI was 32.33 ± 7.07 kg/m². The distribution of hips and knees in our study was relatively even (58.78% knees vs. 42.22% hips) and there were a large number of patients who had smoked within six months of their TJA at 46.66% in both the SAT cohort and matched cohort. Of note, the only indications for TJA in our SAT cohort were inflammatory arthritis (2.22%) (rheumatoid or psoriatic arthritis), or osteoarthritis (97.78%); thus, these were the indications matched upon to create our control group.

Table 1.

Matched Demographic Variables

Parameter	SAT patients (n = 45)	Matched control group (n = 180)	p
Age^a	67.56 ± 11.26	67.97 ± 10.98	0.820
Gender^a			1
Male	21 (46.66%)	84 (46.66%)
Female	24 (53.37%)	96 (53.37%)
BMI (kg/m²)^a	32.33 ± 7.07	32.01 ± 6.52	0.766
Joint of TJA^a			1
Hip	19 (42.22%)	76 (42.22%)
Knee	26 (58.78%)	104 (58.78%)
Diabetes^a	7 (15.55%)	28 (15.55%)	1
Smoker^a	21 (46.66%)	84 (46.66%)	1
Indication for TJA^a			1
Inflammatory arthritis	1 (2.22%)	4 (2.22%)
Osteoarthritis	44 (97.78%)	176 (97.78%)

SAT = suppressive antibiotic therapy; BMI = body mass index; TJA = total joint arthroplasty.

Matched variables were gathered at a 1:4 SAT:control ratio. Matching specificity was age (years) ±5, BMI ±5. All other variables were exactly matched.

Table 2 displays the unmatched variables that were compared between our two cohorts. The SAT cohort had higher rates of ASA physical scoring of four and CCI compared to the control group (11.12% vs. 0.55%; p < 0.001) and (4.18 ± 2.58 vs. 3.28 ± 1.59; p = 0.004). In addition, the SAT cohort was more likely to have a history of prior septic joints (native and periprosthetic) (55.56% vs. 1.66%; p < 0.001), and history of antibiotic allergies (42.22% vs. 15.00%; p < 0.001) compared with the control group. Regarding the TJA itself, the SAT group received antibiotic-laden bone cement or antibiotic pearls more often during the new primary TJA compared with the control group (26.67% vs. 6.11%; p < 0.001). Finally, we were unable to detect a difference in the rate of development of PJI at any time point within follow-up between the SAT cohort and control group (2.22% vs. 1.11%; p = 0.561).

Table 2.

Unmatched Variables

Paramenter	SAT patients (n = 45)	Matched control group (n = 180)	p
ASA physical score
2	22 (48.88%)	102 (56.67%)	0.348
3	18 (40.00%)	77 (42.78%)	0.925
4	5 (11.12%)	1 (0.55%)	< 0.001
CCI	4.18 ± 2.58	3.28 ± 1.59	0.004
Operative duration (min)	78.65 ± 25.61	72.95 ± 27.08	0.248
Regular alcohol user	13 (28.88%)	57 (31.67%)	0.718
Autoimmune disease	7 (15.56%)	27 (15.00%)	0.925
Injection drug use	0 (0%)	1 (0.55%)	1
Any prior septic joint	25 (55.56%)	3 (1.66%)	< 0.001
Native joint	1 (4.00%)	3 (100%)	0.001
Prosthetic joint	24 (96%)	0 (0%)	< 0.001
Any antibiotic allergy	19 (42.22%)	27 (15.00%)	< 0.001
Any β-lactam allergy	9 (43.37%)	21 (77.78%)	0.058
Other allergies	10 (56.63%)	6 (22.22%)	0.058
Use of antibiotic-laden bone cement or pearls during new TJA	12 (26.67%)	11 (6.11%)	< 0.001
Follow-up duration (y)	4.10 ± 3.42	5.50 ± 4.06	0.034
Year of surgery	2014.63 ± 4.56	2016.62 ± 4.06	0.008
PJI after new TJA	1 (2.22%)	2 (1.11%)	0.561

SAT = suppressive antibiotic therapy; ASA = American Society of Anesthesiologists; CCI = Charlson comorbidity index; TJA = total joint arthroplasty; PJI = peri-prosthetic joint infection.

Table 3 depicts further details of the suppressed infections and primary TJAs in our SAT cohort. There were 22 patients who underwent a primary TJA who were receiving SAT for previous PJI of a different hip, knee, or shoulder TJA. In a subanalysis of these 22 patients, one experienced a PJI in the new primary TJA at a rate of 4.54%. When these 22 patients receiving SAT for previous PJI were compared the 88 respective control patients, we were unable to identify a significant difference in PJI rates (4.54% vs. 0%; p = 0.2) (Table 4). No cases of PJI were seen in patients receiving SAT for non-PJI indications. Coverage for recurrent urinary tract infections and cellulitis together accounted for 15.56% of the indications for SAT and were categorized as secondary infection prophylaxis. The remaining 84.44% of patients were receiving SAT for infectious that were presumably ongoing, such as THA and TKA PJI (Table 3). The most common reason for SAT in patients with ongoing infection was THA PJI management, at 36.84% of cases. Other indications for suppression ranged from endovascular infection (13.16%), spinal hardware infections (10.53%), and osteomyelitis (7.89%). The most common organism that was being suppressed was methicillin-susceptible Staphylococcus aureus (MSSA; 22.22%). Of note, 28.88% of suppressed infections were polymicrobial (>2 organisms). The most commonly used medication classes used for oral SAT were β-lactams (31.11%) followed by tetracyclines (26.67%; Table 3).

Table 3.

Details of SAT Patient Clinical Courses

Paramenter	Chronic suppression patients (n = 45)
Indication for SAT
Secondary infectious prophylaxis	7 (15.56%)
Recurrent UTI	6 (85.71%)
Recurrent cellulitis	1 (14.29%)
Ongoing infection management	38 (84.44%)
Previous PJI	22 (48.88%)
THA PJI	14 (36.84%)
TSA PJI	4 (10.53%)
TKA PJI	4 (10.53%)
Endovascular infection (grafts, aneurysms, implantable devices)	5 (13.16%)
Multiple actively infected loci	4 (10.53%)
Spinal hardware infections	4 (10.53%)
Osteomyelitis	3 (7.89%)
Infectious organism being suppressed
MSSA	10 (22.22%)
MRSA	4 (8.89%)
CoNS	2 (4.44%)
Streptococcus	5 (11.11%)
Cutibacterium	4 (8.89%)
Gram-negative organism	5 (11.11%)
Polymicrobial	13 (28.88%)
Culture-negative	2 (4.44%)
Agents used for oral SAT
β-lactams	14 (31.11%)
Tetracyclines	12 (26.67%)
Macrolides	2 (4.44%)
Sulfonamides	6 (13.33%)
Nitrofurantoin	4 (8.89%)
Fluoroquinolones	2 (4.44%)
Clindamycin	1 (2.22%)
Multiple agents	4 (8.89%)
Pre-operative serum ESR of new TJA	34.00 ± 33.39
Pre-operative serum CRP of new TJA	7.60 ± 10.63
Peri-operative antibiotic regimen of new TJA
Cefazolin	35 (77.77%)
Cefazolin plus vancomycin	5 (11.11%)
Clindamycin	3 (6.67%)
Ciprofloxacin	2 (4.44%)
Clindamycin plus vancomycin	1 (2.22%)
Antibiotic allergies
No allergies	26 (57.78%)
Multiple antibiotic allergies	5 (11.11%)
Sulfa antibiotics	4 (8.89%)
Penicillins	5 (11.11%)
Vancomycin	1 (2.22%)
Macrolides	1 (2.22%)
Fluoroquinolones	1 (2.22%)
Rifampin	1 (2.22%)
Daptomycin	1 (2.22%)

SAT = suppressive antibiotic therapy; UTI = urinary tract infection; TSA = total shoulder arthroplasty; THA = total hip arthroplasty; TKA = total knee arthroplasty; MSSA = methicillin-susceptible Staphylococcus aureus; MRSA = methicillin-resistant Staphylococcus aureus; CoNS = coagulase-negative staphylococci; ESR = erythrocyte sedimentation rate in mm/hr; CRP = C-reactive protein in mg/L.

Table 4.

Subanalysis of Patients on SAT for PJI

Paramenter	Patients on SAT for PJI (n = 22)	Matched control group (n = 88)	p
ASA physical score
2	10 (45.45%)	50 (56.81%)	0.338
3	11 (50.00%)	37 (42.04%)	0.501
4	1 (4.54%)	1 (1.13%)	0.284
CCI	3.86 ± 2.36	3.09 ± 1.53	0.061
Operative duration (min)	79.84 ± 27.61	74.12 ± 28.36	0.424
Regular alcohol user	6 (27.27%)	28 (31.81%)	0.679
Autoimmune disease	1 (4.54%)	13 (14.77%)	0.197
Injection drug use	0 (0.00%)	0 (0.00%)	1
Any antibiotic allergy	9 (40.90%)	13 (14.77%)	0.006
Any β-lactam allergy	4 (18.18%)	11 (12.50%)	0.487
Other allergies	5 (22.72%)	2 (2.27%)	< 0.001
Use of antibiotic-laden bone cement or pearls during new TJA	8 (36.36%)	5 (5.68%)	< 0.001
Follow-up duration (y)	4.25 ± 3.63	4.80 ± 2.00	0.387
Year of surgery	2017 ± 3.57	2015 ± 1.32	0.003
PJI after new TJA	1 (4.54%)	0 (0.00%)	0.200

SAT = suppressive antibiotic therapy; ASA = American Society of Anesthesiologists; CCI = Charlson comorbidity index; TJA = total joint arthroplasty; PJI = peri-prosthetic joint infection.

For the primary TJA, patients receiving SAT had an average pre-operative serum ESR and CRP of 34.00 ± 33.39 mm/hr (reference, 0–13 mm/hr) and 7.60 ± 10.63 mg/L (reference, <8.0 mg/L). The most commonly used peri-operative antibiotic regimen of the new TJA in the SAT cohort was cefazolin at 77.77% and five (11.11%) patients received cefazolin plus vancomycin. Althugh not displayed in our tables, compared with the matched control cohort, the number of patients who received only cefazolin peri-operatively for infection prophylaxis was higher in the control cohort compared with the SAT cohort (160/180 [88.88%] vs. 35/45 [77.77%]; p = 0.049).

Discussion

There is a paucity of data on risk of PJIs in patients undergoing primary TJA who are receiving SAT for previously diagnosed PJI or other chronic infections. Peri-prosthetic joint infections are a devastating outcome of TJA and the lack of data around primary TJA in patients with SAT make decisions increasingly difficult for both patients and surgeons. In our study, we were unable to detect a difference in PJI rates between our overall SAT cohort and the matched cohort (2.22% vs. 1.11%; p = 0.561) as well as in a subgroup of patients receiving SAT for previous PJI compared with a matched cohort (4.54% vs. 0%; p = 0.2). Given our study's sample size and statistical power, we are unable to make statements regarding PJI risk in a SAT cohort, although our data are promising and may serve as grounds for future multicenter studies to evaluate PJI risk in patients receiving SAT undergoing primary TJA.

Unsurprisingly, the patients in our SAT cohort were more medically ill than our matched cohort. This is evidenced by differences in the number of patients who received the ASA physical score of four and the average CCI, both of which were higher in the SAT cohort. The patients who were receiving SAT were also more likely to have any antibiotic allergy and be given antibiotic-laden bone cement or pearls during their new TJA compared with the control cohort. We believe that the high antibiotic allergy prevalence in the SAT group is likely representative of overall antibiotic exposure and a high overall number of inpatient hospital encounters experienced by these patients. On the other hand, the higher number of patients in the SAT cohort given antibiotic-laden bone cement/pearl use during the primary TJAs is difficult to interpret, as the patients in the patients had their TJAs performed in a large range of years under varying departmental guidelines and individual surgeon preferences for patients with previous unresolved infections. We also found that patients in the SAT cohort were less likely to be given a primary TJA peri-operative antibiotic regimen of only cefazolin compared with the matched control cohort, which may be representative of the higher rate of antibiotic allergies seen in the SAT cohort. This is important to note as non-cefazolin antibiotic administration in the peri-operative setting has often been associated with increased PJI risk itself.^24–27

Oral SAT has been studied extensively in settings of active PJI in TJA (e.g., DAIR and two-stage revision), has generally shown favorable results as a means to improve infection-free survival in patients after surgical clearance of the active infection.^{9,11,12,28,29} However, only one other study to our knowledge has evaluated risk of PJI in a new primary TJA when patients were actively receiving oral SAT.¹⁸ Chalmers et al.¹⁸ found a much higher rate of PJI in their SAT cohort (21.43%) compared with our SAT cohort's rate (2.22%). The rate of PJI in the matched control cohorts were similar in the study by Chalmers et al.¹⁸ (1.4%) and our study (1.1%). However, there are several differences worth noting between our studies. We had a larger sample size of patients receiving SAT (45 vs. 28), included both THA and TKA patients (compared with TKA patients alone), and included patients receiving SAT for any cause including urinary tract infection, endovascular graft, spine surgery, and PJI. In our study, 53.5% of patients in our SAT cohort had a history of prior PJI including THA, TKA, and total shoulder arthroplasty (TSA), whereas all patients in the study by Chalmers et al.¹⁸ had a history of prior PJI. We hypothesize that both the differences in follow-up duration and specific infectious indications for SAT may play a role in the difference in PJI rates seen between these two studies, although the differences in PJI rates could be entirely explained by differing institutional SAT prescribing guidelines, patient genetics/comorbidities, or microbe characteristics not accounted for in either study.

One possibility for the difference in PJI rates between the studies is that by including seven of 45 patients with SAT for secondary infectious prophylaxis such as recurrent urinary tract infection and cellulitis, we may have analyzed patients who spend less time actively infected and at risk for hematogenous seeding compared with patients with actively suppressed chronic infections. Nevertheless, in the 38 patients who had active chronic infections in our SAT cohort, we only found one PJI, at a rate of 2.63%. The other possibility is that by our study having a shorter follow up duration compared to Chalmers et al. (6 years), we were unable to detect PJIs that may have occurred after the follow up period. This is worth noting, as one would expect a hematogenous route PJI stemming from the distant suppressed infection to be the most likely source of PJI in patients on SAT. As hematogenous PJIs have been found to occur at mean 3.91 years post-TJA in some studies, our study with mean follow-up duration of 4.1 years may miss a small number of PJI cases that occur more than four years post-operatively.³⁰

There are several limitations to our study. This is a retrospective study at a large tertiary care center and the findings may not be easily translated to smaller community practices. To include as many patients as possible in our SAT cohort, we had to include patients with heterogeneity of surgical techniques and indications for SAT. It is unlikely that the variety of infections included for oral SAT indications in our cohort all pose the same risk of seeding a new primary TJA and causing PJI, but because of small sample sizes, we chose to include as many cases of SAT as possible. In addition, despite our relatively large cohort of SAT patients (n = 45) matched to controls at 1:4 (n = 180), the rate of PJI after new primary TJA in our study was low (n = 3), thus limiting our ability to perform a regression, multiple subgroup analyses, or make statements about PJI risk in the SAT cohort. To make any conclusions about the risk of PJI of a new primary TJA in patients on SAT, future studies with larger sample sizes, potentially including multiple centers, are warranted. Despite these limitations, this is the largest study evaluating risk of PJI in patients receiving SAT undergoing primary TJA.

Conclusions

This study found that patients on long-term SAT had a 2.22% rate of PJI after primary TJA at mean follow-up of 4.1 years. As this clinical scenario is rare but potentially devastating for patients, future large-scale studies can be performed to understand risk of PJI in this population subset compared with matched controls.

Footnotes

Authors' Contributions

Writing–original draft: Humphrey, Katakam. Writing–review and editing: Humphrey, Nelson, Heng, Melnic. Formal analysis: Humphrey. Investigation: Humphrey. Methodology: Dunahoe, Melnic. Conceptualization: Dunahoe, Nelson, Katakam, Melnic. Data curation: Dunahoe. Supervision: Nelson, Katakam, Heng, Bedair. Visualization: Park, Heng, Bedair, Melnic.

Project administration: Park. Resources: Bedair.

Funding Information

There was no funding for this study.

Author Disclosure Statement

Melnic is a speaker and paid consultant for Smith & Nephew and receives research support from Zimmer Biomet. Bedair receives royalties from and is a paid consultant for Exactech and Smith & Nephew, has stock options in Exactech, receives research support from Zimmer Biomet, and receives royalties from Wolters Kluwer. Heng is a paid consult for Zimmer Biomet, Inc. These conflicts of interest are stated here but are unrelated to the present study. The remaining authors have no conflicts of interest to disclose.

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